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NCT Number: NCT04539964

Vagus Nerve Stimulation for Moderate to Severe Rheumatoid Arthritis

The RESET-RA study will assess the safety and efficacy of the SetPoint System (study device) for the treatment of adult patients with active, moderate to severe rheumatoid arthritis who have had an inadequate response or intolerance to biologic or targeted synthetic Disease-Modifying Anti-Rheumatic Drugs (DMARDs). The study device contains a miniaturized stimulator (implant) that is surgically placed under general anesthesia on the vagus nerve through a small incision on the left side of the neck (implant procedure). The study will enroll up to 250 subjects at up to 45 sites. All eligible subjects will undergo the implant procedure. Half of the subjects will receive active stimulation (treatment) and the other half will receive non-active stimulation (control). After completing primary endpoint assessments at Week 12, there will be a one-way crossover of control subjects to active stimulation and a 252-week open-label follow-up with all subjects (treatment and control) receiving active stimulation to evaluate long-term safety.

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Key information

Conditions

Rheumatoid Arthritis Arthritis Arthritis, Rheumatoid Autoimmune Diseases Connective Tissue Diseases Immune System Diseases Joint Diseases Musculoskeletal Diseases Rheumatic Diseases Skin and Connective Tissue Diseases

Age range

22 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Arizona Arthritis ans Rheumatology Research, PPLC, Mesa, Arizona, United States

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About this study

The RESET-RA study is an operationally seamless, 2-stage, randomized, double-blind, sham-controlled, multicenter pivotal study enrolling up to 250 subjects at up to 45 study centers across the U.S. The study will assess the safety and efficacy of the SetPoint System (study device) for the treatment of adult patients with active, moderate to severe rheumatoid arthritis (RA) who have had an inadequate response, loss of response or intolerance to biologic or targeted synthetic Disease-Modifying Anti-Rheumatic Drugs (DMARDs). The study device contains a miniaturized stimulator (implant) that is surgically implanted inside the left side of the neck on the vagus nerve (implant procedure). The implant delivers a small amount of electricity (stimulation) to the nerve. All eligible subjects will undergo the surgery under general anesthesia. Half of the subjects will receive active stimulation (the treatment group) and the other half will receive non-active stimulation (the control group). Stimulation will be delivered for 1 min once per day for 12 weeks. After completing primary endpoint assessments at Week 12, there will be a one-way crossover of control subjects to active stimulation and a 252-week open-label follow-up with all subjects (treatment and control) receiving active stimulation to evaluate long-term safety. Blinding will be maintained until the last enrolled and randomized subject in Stage 2 completes Week 12 assessments, and the study database is locked.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 22-75 years of age at screening
  • Active moderate or severe RA, defined as at least 4/28 tender and 4/28 swollen joints
  • Demonstrated an inadequate response, loss of response, or intolerance to 1 or more approved for rheumatoid arthritis biologic or targeted synthetic Disease-Modifying Anti-Rheumatic Drugs (DMARDs), including Janus kinase inhibitors (JAKi)
  • Receiving treatment with at least 1 conventional synthetic DMARD for at least 12 weeks and on a continuous non-changing dose and route of administration for at least 4 weeks prior to Screening and able to continue the same stable dose through Week 12

Exclusion criteria

  • Untreated or poorly controlled psychiatric illness or history of substance abuse
  • Significant immunodeficiency due to underlying illness
  • History of stroke or transient ischemic attack, or diagnosis of cerebrovascular fibromuscular dysplasia
  • Clinically significant cardiovascular disease
  • Neurological syndromes, including multiple sclerosis, Alzheimer's disease, or Parkinson's disease
  • Uncontrolled fibromyalgia
  • History of left or right carotid surgery
  • History of unilateral or bilateral vagotomy, partial or complete splenectomy
  • Recurrent vasovagal syncope episodes
  • Current, regular use of tobacco products
  • Hypersensitivity/allergy to MRI contrast agents and/or unable to perform MRI

Treatment and study plan

Implant Procedure

Procedure

The SetPoint System (study device) contains a miniaturized stimulator (implant) that is surgically implanted inside the left side of the neck on the vagus nerve (implant procedure). All eligible subjects will undergo the surgery under general anesthesia in outpatient settings.

Other names: Surgical placement of vagus nerve stimulator inside the neck

Conventional Synthetic DMARD

Drug

All subjects will continue to take at least one type of conventional synthetic DMARD at the same stable dose as for 4 weeks prior to consent

Other names: Background therapy with conventional synthetic DMARD

Active stimulation

Device

Active stimulation for 1 min once per day

Non-active stimulation

Device

Non-active stimulation for 1 min once per day

Primary outcomes

  1. the American College of Rheumatology (ACR) 20 Response

    Time frame: Week 12

    Response is defined as achieving at least 20% improvement from baseline to Week 12 in tender and swollen joint counts of 28 joints (scale 0=best to 28=worst) and 3 out of the following 5 measures: Health Assessment Questionnaire Disability Index (HAQ-DI) score (scale 0=no difficulty to 3=unable to do), subject global assessment (0=best to 10=worst), subject pain (0=no pain to 10=worst), evaluator's global assessment (0=best to 10=worst), or high sensitivity C-reactive protein (hsCRP) concentration (mg/L).

Secondary outcomes

  1. DAS28-CRP Good or Moderate Response as Defined by European League Against Rheumatism (EULAR)

    Time frame: Week 12

    The Disease Activity Score in 28 joints calculated with C-reactive protein (DAS28-CRP) good or moderate response as defined by EULAR based on a composite score of 4 items: tender and swollen joint counts of 28 joints (scale 0=best to 28=worst), subject global assessment (0=best to 10=worst) and high-sensitivity C-reactive protein (hsCRP) concentration (mg/L). A total score ranges from 0 to 10 and is computed as follows:

    DAS28-CRP = 0.56 * sqrt(TJC28) + 0.28 * sqrt(SJC28) + 0.36 * ln(CRP+1) + 0.014 * SGA + 0.96

    A subject is considered having a moderate treatment response if:

    • DAS28-CRP score improvement from baseline to Week 12 is > 0.6 and ≤ 1.2, and the DAS28-CRP score at Week 12 is ≤ 5.1; or
    • DAS28-CRP score improvement from baseline to Week 12 is > 1.2, and the DAS28-CRP score at Week 12 is > 3.2.

    A subject is considered having a good treatment response if:

    • DAS28-CRP score improvement from baseline to Week 12 is > 1.2 and the DAS28-CRP score at Week 12 is ≤ 3.2

  2. DAS28-CRP Response (MCID -1.2) at Week 12

    Time frame: Week 12

    The Disease Activity Score in 28 joints calculated with C-reactive protein (DAS28-CRP) response is based on the minimal clinically important difference (MCID) of -1.2 from baseline.

    DAS28-CRP is based on a composite score of 4 items: tender and swollen joint counts of 28 joints (scale 0=best to 28=worst), subject global assessment (0=best to 10=worst) and high-sensitivity C-reactive protein (hsCRP) concentration (mg/L). A total score ranges from 0 to 10 and is computed as follows:

    DAS28-CRP = 0.56 * sqrt(TJC28) + 0.28 * sqrt(SJC28) + 0.36 * ln(CRP+1) + 0.014 * SGA + 0.96

  3. Health Assessment Questionnaire Disability Index (HAQ-DI) Response (MCID -0.22)

    Time frame: Week 12

    HAQ-DI response based on the MCID of -0.22 from baseline.

    The HAQ-DI is a questionnaire validated for RA self-assessment by subjects that contains 20 questions in the following 8 functional areas:

    • Dressing and grooming
    • Arising
    • Eating
    • Walking
    • Hygiene
    • Reach
    • Grip
    • Common daily activities

    Scoring within each functional area is from 0 (without any difficulty) to 3 (unable to do). The total score is obtained by summing 8 area scores and dividing by 8. The total HAQ-DI score ranges from 0 to 3 and corresponds to the current degree of disability:

    • 0 to < 1 Mild difficulties to moderate disability
    • 1 to < 2 Moderate disability
    • 2 to 3 Severe to very severe disability

  4. ACR20 Response at Week 12 From Day 0

    Time frame: Week 12

    Response is defined as achieving at least 20% improvement from Day 0 to Week 12 in tender and swollen joint counts of 28 joints (scale 0=best to 28=worst) and 3 out of the following 5 measures: Health Assessment Questionnaire Disability Index (HAQ-DI) score (scale 0=no difficulty to 3=unable to do), subject global assessment (0=best to 10=worse), subject pain (0=no pain to 10=worst), evaluator's global assessment (0=best to 10=worst), or high sensitivity C-reactive protein (hsCRP) concentration (mg/mL).

Other outcomes

  1. Bone Erosion Progression, All Completers

    Time frame: Week 12

    RAMRIS is a standardized system for RA MRI scoring of 4 different types of joint pathologies in the wrist and the hand. A total score for each pathology is generated by the summation of individual joint/bone scores as follows:

    • Synovitis: 8 joints each scored on a scale from 0 = normal to 3 = severe, resulting in a total score from 0 to 24.
    • Bone erosion: 25 bones each scored on a scale from 0 (0-10% eroded volume) to 10 (91-100% eroded volume), resulting in a total score from 0 to 250.
    • Osteitis: 25 bones scored on a scale from 0 (no osteitis) to 3 (68-100% of bone volume involved), resulting in a total score from 0 to 75.
    • CARLOS (cartilage loss): 25 joints each scored on a scale from 0 (no damage) to 4 (complete ankylosis or fusion), resulting in a total score from 0 to 100.

    The proportion of bone erosion progressors is the % subjects with an increase of > 0.5 on the bone erosion score, comparing baseline to Week 12. An increase of > 0.5 represents disease progression.

  2. Bone Erosion Progression, All Completers With Erosive Phenotype

    Time frame: Week 12

    RAMRIS is a standardized system for RA MRI scoring of 4 different types of joint pathologies in the wrist and the hand. A total score for each pathology is generated by the summation of individual joint/bone scores as follows:

    • Synovitis: 8 joints each scored on a scale from 0 = normal to 3 = severe, resulting in a total score from 0 to 24.
    • Bone erosion: 25 bones each scored on a scale from 0 (0-10% eroded volume) to 10 (91-100% eroded volume), resulting in a total score from 0 to 250.
    • Osteitis: 25 bones scored on a scale from 0 (no osteitis) to 3 (68-100% of bone volume involved), resulting in a total score from 0 to 75.
    • CARLOS (cartilage loss): 25 joints each scored on a scale from 0 (no damage) to 4 (complete ankylosis or fusion), resulting in a total score from 0 to 100.

    The proportion of bone erosion progressors is the % subjects with an increase of > 0.5 on the bone erosion score, comparing baseline to Week 12. An increase of > 0.5 represents disease progression.

  3. Bone Erosion Progression, All Completers That Previously Only Failed 1 b/tsDMARD

    Time frame: Week 12

    RAMRIS is a standardized system for RA MRI scoring of 4 different types of joint pathologies in the wrist and the hand. A total score for each pathology is generated by the summation of individual joint/bone scores as follows:

    • Synovitis: 8 joints each scored on a scale from 0 = normal to 3 = severe, resulting in a total score from 0 to 24.
    • Bone erosion: 25 bones each scored on a scale from 0 (0-10% eroded volume) to 10 (91-100% eroded volume), resulting in a total score from 0 to 250.
    • Osteitis: 25 bones scored on a scale from 0 (no osteitis) to 3 (68-100% of bone volume involved), resulting in a total score from 0 to 75.
    • CARLOS (cartilage loss): 25 joints each scored on a scale from 0 (no damage) to 4 (complete ankylosis or fusion), resulting in a total score from 0 to 100.

    The proportion of bone erosion progressors is the % subjects with an increase of > 0.5 on the bone erosion score, comparing baseline to Week 12. An increase of > 0.5 represents disease progression.

  4. Change in Erosion Score, All Completers

    Time frame: Week 12

    RAMRIS is a standardized system for RA MRI scoring of 4 different types of joint pathologies in the wrist and the hand (synovitis, bone erosion, osteitis, and cartilage loss). A total score for each pathology is generated by the summation of individual joint/bone scores:

    • Bone erosion: 25 bones each scored on a scale from 0 (0-10% eroded volume) to 10 (91-100% eroded volume), resulting in a total score from 0 to 250.

  5. Change in Erosion Score, All Completers With Erosive Phenotype

    Time frame: Week 12

    RAMRIS is a standardized system for RA MRI scoring of 4 different types of joint pathologies in the wrist and the hand (synovitis, bone erosion, osteitis, and cartilage loss). A total score for each pathology is generated by the summation of individual joint/bone scores:

    • Bone erosion: 25 bones each scored on a scale from 0 (0-10% eroded volume) to 10 (91-100% eroded volume), resulting in a total score from 0 to 250.

  6. Change in Erosion Score, All Completers That Previously Only Failed 1 b/tsDMARD

    Time frame: Week 12

    RAMRIS is a standardized system for RA MRI scoring of 4 different types of joint pathologies in the wrist and the hand (synovitis, bone erosion, osteitis, and cartilage loss). A total score for each pathology is generated by the summation of individual joint/bone scores:

    • Bone erosion: 25 bones each scored on a scale from 0 (0-10% eroded volume) to 10 (91-100% eroded volume), resulting in a total score from 0 to 250.

  7. Change in Synovitis Score, All Completers

    Time frame: Week 12

    RAMRIS is a standardized system for RA MRI scoring of 4 different types of joint pathologies in the wrist and the hand (synovitis, bone erosion, osteitis, and cartilage loss). A total score for each pathology is generated by the summation of individual joint/bone scores:

    • Synovitis: 8 joints each scored on a scale from 0 = normal to 3 = severe, resulting in a total score from 0 to 24.

  8. Change in Synovitis Score, All Completers With Erosive Phenotype

    Time frame: Week 12

    RAMRIS is a standardized system for RA MRI scoring of 4 different types of joint pathologies in the wrist and the hand (synovitis, bone erosion, osteitis, and cartilage loss). A total score for each pathology is generated by the summation of individual joint/bone scores:

    • Synovitis: 8 joints each scored on a scale from 0 = normal to 3 = severe, resulting in a total score from 0 to 24.

  9. Change in Synovitis Score, All Completers That Previously Only Failed 1 b/tsDMARD

    Time frame: Week 12

    RAMRIS is a standardized system for RA MRI scoring of 4 different types of joint pathologies in the wrist and the hand (synovitis, bone erosion, osteitis, and cartilage loss). A total score for each pathology is generated by the summation of individual joint/bone scores:

    • Synovitis: 8 joints each scored on a scale from 0 = normal to 3 = severe, resulting in a total score from 0 to 24.

  10. Change in Osteitis Score, All Completers

    Time frame: Week 12

    RAMRIS is a standardized system for RA MRI scoring of 4 different types of joint pathologies in the wrist and the hand (synovitis, bone erosion, osteitis, and cartilage loss). A total score for each pathology is generated by the summation of individual joint/bone scores:

    • Osteitis: 25 bones scored on a scale from 0 (no osteitis) to 3 (68-100% of bone volume involved), resulting in a total score from 0 to 75.

  11. Change in Osteitis Score, All Completers With Erosive Phenotype

    Time frame: Week 12

    RAMRIS is a standardized system for RA MRI scoring of 4 different types of joint pathologies in the wrist and the hand (synovitis, bone erosion, osteitis, and cartilage loss). A total score for each pathology is generated by the summation of individual joint/bone scores:

    • Osteitis: 25 bones scored on a scale from 0 (no osteitis) to 3 (68-100% of bone volume involved), resulting in a total score from 0 to 75.

  12. Change in Osteitis Score, All Completers That Previously Only Failed 1 b/tsDMARD

    Time frame: Week 12

    RAMRIS is a standardized system for RA MRI scoring of 4 different types of joint pathologies in the wrist and the hand (synovitis, bone erosion, osteitis, and cartilage loss). A total score for each pathology is generated by the summation of individual joint/bone scores:

    • Osteitis: 25 bones scored on a scale from 0 (no osteitis) to 3 (68-100% of bone volume involved), resulting in a total score from 0 to 75.

  13. Clinical Disease Activity Index (CDAI) Low Disease Activity (LDA) or Remission

    Time frame: Week 12

    The CDAI score is based on 4 items:

    • TJC28, tender joint count of 28 joints (scale 0=best to 28=worst)
    • SJC28, swollen joint count of 28 joints (scale 0=best to 28=worst)
    • SGA, subject global assessment (0=best to 10=worst)
    • EGA, evaluator's global assessment (0=best to 10=worst)

    The CDAI score is calculated as follows and ranges from 0 to 76:

    • CDAI = TJC28 + SJC28 + SGA + EGA

    The CDAI score corresponds to the current RA activity:

    • 0 to ≤ 2.8 Remission
    • >2.8 to ≤ 10 Low disease activity (LDA)
    • >10 to ≤ 22 Moderate disease activity
    • > 22 High disease activity

  14. DAS28-CRP Low Disease Activity (LDA) or Remission

    Time frame: Week 12

    The Disease Activity Score in 28 joints calculated with C-reactive protein (DAS28-CRP) score is a composite index providing a measure of disease activity, comprising:

    • TJC28, tender joint count of 28 joints (scale 0=best to 28=worst)
    • SJC28, swollen joint count of 28 joints (scale 0=best to 28=worst)
    • SGA, subject global assessment (0=best to 10=worst)
    • hsCRP (mg/L), high sensitivity C-reactive protein concentration (mg/L)

    A total score ranges from 0 to 10 and is computed as follows:

    DAS28-CRP = 0.56 * sqrt(TJC28) + 0.28 * sqrt(SJC28) + 0.36 * ln(CRP+1) + 0.014 * SGA + 0.96

    The DAS28-CRP score corresponds to the current RA activity:

    • 0 to < 2.6 Remission
    • 2.6 to < 3.2 LDA
    • 3.2 to ≤ 5.1 Moderate activity
    • > 5.1 High activity

  15. the American College of Rheumatology (ACR) 20 Response, All Completers

    Time frame: Week 24

    Response is defined as achieving at least 20% improvement from baseline to Week 12 in tender and swollen joint counts of 28 joints (scale 0=best to 28=worst) and 3 out of the following 5 measures: Health Assessment Questionnaire Disability Index (HAQ-DI) score (scale 0=no difficulty to 3=unable to do), subject global assessment (0=best to 10=worst), subject pain (0=no pain to 10=worst), evaluator's global assessment (0=best to 10=worst), or high sensitivity C-reactive protein (hsCRP) concentration (mg/L).

  16. the American College of Rheumatology (ACR) 20 Response, Non-augmented

    Time frame: Week 24

    Response is defined as achieving at least 20% improvement from baseline to Week 12 in tender and swollen joint counts of 28 joints (scale 0=best to 28=worst) and 3 out of the following 5 measures: Health Assessment Questionnaire Disability Index (HAQ-DI) score (scale 0=no difficulty to 3=unable to do), subject global assessment (0=best to 10=worst), subject pain (0=no pain to 10=worst), evaluator's global assessment (0=best to 10=worst), or high sensitivity C-reactive protein (hsCRP) concentration (mg/L).

  17. Clinical Disease Activity Index (CDAI) Low Disease Activity (LDA) or Remission, All Completers

    Time frame: Week 24

    The CDAI score is based on 4 items:

    • TJC28, tender joint count of 28 joints (scale 0=best to 28=worst)
    • SJC28, swollen joint count of 28 joints (scale 0=best to 28=worst)
    • SGA, subject global assessment (0=best to 10=worst)
    • EGA, evaluator's global assessment (0=best to 10=worst)

    The CDAI score is calculated as follows and ranges from 0 to 76:

    • CDAI = TJC28 + SJC28 + SGA + EGA

    The CDAI score corresponds to the current RA activity:

    • 0 to ≤ 2.8 Remission
    • >2.8 to ≤ 10 Low disease activity (LDA)
    • >10 to ≤ 22 Moderate disease activity
    • > 22 High disease activity

  18. Clinical Disease Activity Index (CDAI) Low Disease Activity (LDA) or Remission, Non-augmented

    Time frame: Week 24

    The CDAI score is based on 4 items:

    • TJC28, tender joint count of 28 joints (scale 0=best to 28=worst)
    • SJC28, swollen joint count of 28 joints (scale 0=best to 28=worst)
    • SGA, subject global assessment (0=best to 10=worst)
    • EGA, evaluator's global assessment (0=best to 10=worst)

    The CDAI score is calculated as follows and ranges from 0 to 76:

    • CDAI = TJC28 + SJC28 + SGA + EGA

    The CDAI score corresponds to the current RA activity:

    • 0 to ≤ 2.8 Remission
    • >2.8 to ≤ 10 Low disease activity (LDA)
    • >10 to ≤ 22 Moderate disease activity
    • > 22 High disease activity

  19. DAS28-CRP Low Disease Activity (LDA) or Remission, All Completers

    Time frame: Week 24

    The Disease Activity Score in 28 joints calculated with C-reactive protein (DAS28-CRP) score is a composite index providing a measure of disease activity, comprising:

    • TJC28, tender joint count of 28 joints (scale 0=best to 28=worst)
    • SJC28, swollen joint count of 28 joints (scale 0=best to 28=worst)
    • SGA, subject global assessment (0=best to 10=worst)
    • hsCRP (mg/L), high sensitivity C-reactive protein concentration (mg/L)

    A total score ranges from 0 to 10 and is computed as follows:

    DAS28-CRP = 0.56 * sqrt(TJC28) + 0.28 * sqrt(SJC28) + 0.36 * ln(CRP+1) + 0.014 * SGA + 0.96

    The DAS28-CRP score corresponds to the current RA activity:

    • 0 to < 2.6 Remission
    • 2.6 to < 3.2 LDA
    • 3.2 to ≤ 5.1 Moderate activity
    • > 5.1 High activity

  20. DAS28-CRP Low Disease Activity (LDA) or Remission, Non-augmented

    Time frame: Week 24

    The Disease Activity Score in 28 joints calculated with C-reactive protein (DAS28-CRP) score is a composite index providing a measure of disease activity, comprising:

    • TJC28, tender joint count of 28 joints (scale 0=best to 28=worst)
    • SJC28, swollen joint count of 28 joints (scale 0=best to 28=worst)
    • SGA, subject global assessment (0=best to 10=worst)
    • hsCRP (mg/L), high sensitivity C-reactive protein concentration (mg/L)

    A total score ranges from 0 to 10 and is computed as follows:

    DAS28-CRP = 0.56 * sqrt(TJC28) + 0.28 * sqrt(SJC28) + 0.36 * ln(CRP+1) + 0.014 * SGA + 0.96

    The DAS28-CRP score corresponds to the current RA activity:

    • 0 to < 2.6 Remission
    • 2.6 to < 3.2 LDA
    • 3.2 to ≤ 5.1 Moderate activity
    • > 5.1 High activity

  21. Health Assessment Questionnaire Disability Index (HAQ-DI) MCID Response, All Completers

    Time frame: Week 24

    HAQ-DI response based on the MCID of -0.22 from baseline.

    The HAQ-DI is a questionnaire validated for RA self-assessment by subjects that contains 20 questions in the following 8 functional areas:

    • Dressing and grooming
    • Arising
    • Eating
    • Walking
    • Hygiene
    • Reach
    • Grip
    • Common daily activities

    Scoring within each functional area is from 0 (without any difficulty) to 3 (unable to do). The total score is obtained by summing 8 area scores and dividing by 8. The total HAQ-DI score ranges from 0 to 3 and corresponds to the current degree of disability:

    • 0 to < 1 Mild difficulties to moderate disability
    • 1 to < 2 Moderate disability
    • 2 to 3 Severe to very severe disability

  22. Health Assessment Questionnaire Disability Index (HAQ-DI) Response (MCID -0.22), Non-augmented

    Time frame: Week 24

    HAQ-DI response based on the MCID of -0.22 from baseline.

    The HAQ-DI is a questionnaire validated for RA self-assessment by subjects that contains 20 questions in the following 8 functional areas:

    • Dressing and grooming
    • Arising
    • Eating
    • Walking
    • Hygiene
    • Reach
    • Grip
    • Common daily activities

    Scoring within each functional area is from 0 (without any difficulty) to 3 (unable to do). The total score is obtained by summing 8 area scores and dividing by 8. The total HAQ-DI score ranges from 0 to 3 and corresponds to the current degree of disability:

    • 0 to < 1 Mild difficulties to moderate disability
    • 1 to < 2 Moderate disability
    • 2 to 3 Severe to very severe disability

  23. Study Participants That Are Somewhat to Very Satisfied With the SetPoint System for Treatment of Rheumatoid Arthritis

    Time frame: Week 24

    Patient satisfaction was assessed at Week 24 using five-point Likert rating scale:

    • I am very dissatisfied
    • I am somewhat dissatisfied
    • I am neither satisfied nor dissatisfied
    • I am somewhat satisfied
    • I am very satisfied

  24. Study Participants That Are Neither Satisfied Nor Dissatisfied With the SetPoint System for Treatment of Rheumatoid Arthritis

    Time frame: Week 24

    Patient satisfaction was assessed at Week 24 using five-point Likert rating scale:

    • I am very dissatisfied
    • I am somewhat dissatisfied
    • I am neither satisfied nor dissatisfied
    • I am somewhat satisfied
    • I am very satisfied

  25. Study Participants That Are Somewhat to Very Dissatisfied With the SetPoint System for Treatment of Rheumatoid Arthritis

    Time frame: Week 24

    Patient satisfaction was assessed at Week 24 using five-point Likert rating scale:

    • I am very dissatisfied
    • I am somewhat dissatisfied
    • I am neither satisfied nor dissatisfied
    • I am somewhat satisfied
    • I am very satisfied

  26. Study Participants That Would Recommend the SetPoint System to a Family Member or Friend

    Time frame: Week 24

    Patients were asked a question about whether they would recommend the SetPoint System to family and friends

  27. the American College of Rheumatology (ACR) 20 Response, All Completers

    Time frame: Week 36

    Response is defined as achieving at least 20% improvement from baseline to Week 12 in tender and swollen joint counts of 28 joints (scale 0=best to 28=worst) and 3 out of the following 5 measures: Health Assessment Questionnaire Disability Index (HAQ-DI) score (scale 0=no difficulty to 3=unable to do), subject global assessment (0=best to 10=worst), subject pain (0=no pain to 10=worst), evaluator's global assessment (0=best to 10=worst), or high sensitivity C-reactive protein (hsCRP) concentration (mg/L).

  28. the American College of Rheumatology (ACR) 20 Response, Non-augmented

    Time frame: Week 36

    Response is defined as achieving at least 20% improvement from baseline to Week 12 in tender and swollen joint counts of 28 joints (scale 0=best to 28=worst) and 3 out of the following 5 measures: Health Assessment Questionnaire Disability Index (HAQ-DI) score (scale 0=no difficulty to 3=unable to do), subject global assessment (0=best to 10=worst), subject pain (0=no pain to 10=worst), evaluator's global assessment (0=best to 10=worst), or high sensitivity C-reactive protein (hsCRP) concentration (mg/L).

  29. Clinical Disease Activity Index (CDAI) Low Disease Activity (LDA) or Remission, All Completers

    Time frame: Week 36

    The CDAI score is based on 4 items:

    • TJC28, tender joint count of 28 joints (scale 0=best to 28=worst)
    • SJC28, swollen joint count of 28 joints (scale 0=best to 28=worst)
    • SGA, subject global assessment (0=best to 10=worst)
    • EGA, evaluator's global assessment (0=best to 10=worst)

    The CDAI score is calculated as follows and ranges from 0 to 76:

    • CDAI = TJC28 + SJC28 + SGA + EGA

    The CDAI score corresponds to the current RA activity:

    • 0 to ≤ 2.8 Remission
    • >2.8 to ≤ 10 Low disease activity (LDA)
    • >10 to ≤ 22 Moderate disease activity
    • > 22 High disease activity

  30. Clinical Disease Activity Index (CDAI) Low Disease Activity (LDA) or Remission, Non-augmented

    Time frame: Week 36

    The CDAI score is based on 4 items:

    • TJC28, tender joint count of 28 joints (scale 0=best to 28=worst)
    • SJC28, swollen joint count of 28 joints (scale 0=best to 28=worst)
    • SGA, subject global assessment (0=best to 10=worst)
    • EGA, evaluator's global assessment (0=best to 10=worst)

    The CDAI score is calculated as follows and ranges from 0 to 76:

    • CDAI = TJC28 + SJC28 + SGA + EGA

    The CDAI score corresponds to the current RA activity:

    • 0 to ≤ 2.8 Remission
    • >2.8 to ≤ 10 Low disease activity (LDA)
    • >10 to ≤ 22 Moderate disease activity
    • > 22 High disease activity

  31. DAS28-CRP Low Disease Activity (LDA) or Remission, All Completers

    Time frame: Week 36

    The Disease Activity Score in 28 joints calculated with C-reactive protein (DAS28-CRP) score is a composite index providing a measure of disease activity, comprising:

    • TJC28, tender joint count of 28 joints (scale 0=best to 28=worst)
    • SJC28, swollen joint count of 28 joints (scale 0=best to 28=worst)
    • SGA, subject global assessment (0=best to 10=worst)
    • hsCRP (mg/L), high sensitivity C-reactive protein concentration (mg/L)

    A total score ranges from 0 to 10 and is computed as follows:

    DAS28-CRP = 0.56 * sqrt(TJC28) + 0.28 * sqrt(SJC28) + 0.36 * ln(CRP+1) + 0.014 * SGA + 0.96

    The DAS28-CRP score corresponds to the current RA activity:

    • 0 to < 2.6 Remission
    • 2.6 to < 3.2 LDA
    • 3.2 to ≤ 5.1 Moderate activity
    • > 5.1 High activity

  32. DAS28-CRP Low Disease Activity (LDA) or Remission, Non-augmented

    Time frame: Week 36

    The Disease Activity Score in 28 joints calculated with C-reactive protein (DAS28-CRP) score is a composite index providing a measure of disease activity, comprising:

    • TJC28, tender joint count of 28 joints (scale 0=best to 28=worst)
    • SJC28, swollen joint count of 28 joints (scale 0=best to 28=worst)
    • SGA, subject global assessment (0=best to 10=worst)
    • hsCRP (mg/L), high sensitivity C-reactive protein concentration (mg/L)

    A total score ranges from 0 to 10 and is computed as follows:

    DAS28-CRP = 0.56 * sqrt(TJC28) + 0.28 * sqrt(SJC28) + 0.36 * ln(CRP+1) + 0.014 * SGA + 0.96

    The DAS28-CRP score corresponds to the current RA activity:

    • 0 to < 2.6 Remission
    • 2.6 to < 3.2 LDA
    • 3.2 to ≤ 5.1 Moderate activity
    • > 5.1 High activity

  33. Health Assessment Questionnaire Disability Index (HAQ-DI) MCID Response, All Completers

    Time frame: Week 36

    HAQ-DI response based on the MCID of -0.22 from baseline.

    The HAQ-DI is a questionnaire validated for RA self-assessment by subjects that contains 20 questions in the following 8 functional areas:

    • Dressing and grooming
    • Arising
    • Eating
    • Walking
    • Hygiene
    • Reach
    • Grip
    • Common daily activities

    Scoring within each functional area is from 0 (without any difficulty) to 3 (unable to do). The total score is obtained by summing 8 area scores and dividing by 8. The total HAQ-DI score ranges from 0 to 3 and corresponds to the current degree of disability:

    • 0 to < 1 Mild difficulties to moderate disability
    • 1 to < 2 Moderate disability
    • 2 to 3 Severe to very severe disability

  34. Health Assessment Questionnaire Disability Index (HAQ-DI) Response (MCID -0.22), Non-augmented

    Time frame: Week 36

    HAQ-DI response based on the MCID of -0.22 from baseline.

    The HAQ-DI is a questionnaire validated for RA self-assessment by subjects that contains 20 questions in the following 8 functional areas:

    • Dressing and grooming
    • Arising
    • Eating
    • Walking
    • Hygiene
    • Reach
    • Grip
    • Common daily activities

    Scoring within each functional area is from 0 (without any difficulty) to 3 (unable to do). The total score is obtained by summing 8 area scores and dividing by 8. The total HAQ-DI score ranges from 0 to 3 and corresponds to the current degree of disability:

    • 0 to < 1 Mild difficulties to moderate disability
    • 1 to < 2 Moderate disability
    • 2 to 3 Severe to very severe disability

  35. the American College of Rheumatology (ACR) 20 Response, All Completers

    Time frame: Week 48

    Response is defined as achieving at least 20% improvement from baseline to Week 12 in tender and swollen joint counts of 28 joints (scale 0=best to 28=worst) and 3 out of the following 5 measures: Health Assessment Questionnaire Disability Index (HAQ-DI) score (scale 0=no difficulty to 3=unable to do), subject global assessment (0=best to 10=worst), subject pain (0=no pain to 10=worst), evaluator's global assessment (0=best to 10=worst), or high sensitivity C-reactive protein (hsCRP) concentration (mg/L).

  36. the American College of Rheumatology (ACR) 20 Response, Non-augmented

    Time frame: Week 48

    Response is defined as achieving at least 20% improvement from baseline to Week 12 in tender and swollen joint counts of 28 joints (scale 0=best to 28=worst) and 3 out of the following 5 measures: Health Assessment Questionnaire Disability Index (HAQ-DI) score (scale 0=no difficulty to 3=unable to do), subject global assessment (0=best to 10=worst), subject pain (0=no pain to 10=worst), evaluator's global assessment (0=best to 10=worst), or high sensitivity C-reactive protein (hsCRP) concentration (mg/L).

  37. Clinical Disease Activity Index (CDAI) Low Disease Activity (LDA) or Remission, All Completers

    Time frame: Week 48

    The CDAI score is based on 4 items:

    • TJC28, tender joint count of 28 joints (scale 0=best to 28=worst)
    • SJC28, swollen joint count of 28 joints (scale 0=best to 28=worst)
    • SGA, subject global assessment (0=best to 10=worst)
    • EGA, evaluator's global assessment (0=best to 10=worst)

    The CDAI score is calculated as follows and ranges from 0 to 76:

    • CDAI = TJC28 + SJC28 + SGA + EGA

    The CDAI score corresponds to the current RA activity:

    • 0 to ≤ 2.8 Remission
    • >2.8 to ≤ 10 Low disease activity (LDA)
    • >10 to ≤ 22 Moderate disease activity
    • > 22 High disease activity

  38. Clinical Disease Activity Index (CDAI) Low Disease Activity (LDA) or Remission, Non-augmented

    Time frame: Week 48

    The CDAI score is based on 4 items:

    • TJC28, tender joint count of 28 joints (scale 0=best to 28=worst)
    • SJC28, swollen joint count of 28 joints (scale 0=best to 28=worst)
    • SGA, subject global assessment (0=best to 10=worst)
    • EGA, evaluator's global assessment (0=best to 10=worst)

    The CDAI score is calculated as follows and ranges from 0 to 76:

    • CDAI = TJC28 + SJC28 + SGA + EGA

    The CDAI score corresponds to the current RA activity:

    • 0 to ≤ 2.8 Remission
    • >2.8 to ≤ 10 Low disease activity (LDA)
    • >10 to ≤ 22 Moderate disease activity
    • > 22 High disease activity

  39. DAS28-CRP Low Disease Activity (LDA) or Remission, All Completers

    Time frame: Week 48

    The Disease Activity Score in 28 joints calculated with C-reactive protein (DAS28-CRP) score is a composite index providing a measure of disease activity, comprising:

    • TJC28, tender joint count of 28 joints (scale 0=best to 28=worst)
    • SJC28, swollen joint count of 28 joints (scale 0=best to 28=worst)
    • SGA, subject global assessment (0=best to 10=worst)
    • hsCRP (mg/L), high sensitivity C-reactive protein concentration (mg/L)

    A total score ranges from 0 to 10 and is computed as follows:

    DAS28-CRP = 0.56 * sqrt(TJC28) + 0.28 * sqrt(SJC28) + 0.36 * ln(CRP+1) + 0.014 * SGA + 0.96

    The DAS28-CRP score corresponds to the current RA activity:

    • 0 to < 2.6 Remission
    • 2.6 to < 3.2 LDA
    • 3.2 to ≤ 5.1 Moderate activity
    • > 5.1 High activity

  40. DAS28-CRP Low Disease Activity (LDA) or Remission, Non-augmented

    Time frame: Week 48

    The Disease Activity Score in 28 joints calculated with C-reactive protein (DAS28-CRP) score is a composite index providing a measure of disease activity, comprising:

    • TJC28, tender joint count of 28 joints (scale 0=best to 28=worst)
    • SJC28, swollen joint count of 28 joints (scale 0=best to 28=worst)
    • SGA, subject global assessment (0=best to 10=worst)
    • hsCRP (mg/L), high sensitivity C-reactive protein concentration (mg/L)

    A total score ranges from 0 to 10 and is computed as follows:

    DAS28-CRP = 0.56 * sqrt(TJC28) + 0.28 * sqrt(SJC28) + 0.36 * ln(CRP+1) + 0.014 * SGA + 0.96

    The DAS28-CRP score corresponds to the current RA activity:

    • 0 to < 2.6 Remission
    • 2.6 to < 3.2 LDA
    • 3.2 to ≤ 5.1 Moderate activity
    • > 5.1 High activity

  41. Health Assessment Questionnaire Disability Index (HAQ-DI) MCID Response, All Completers

    Time frame: Week 48

    HAQ-DI response based on the MCID of -0.22 from baseline.

    The HAQ-DI is a questionnaire validated for RA self-assessment by subjects that contains 20 questions in the following 8 functional areas:

    • Dressing and grooming
    • Arising
    • Eating
    • Walking
    • Hygiene
    • Reach
    • Grip
    • Common daily activities

    Scoring within each functional area is from 0 (without any difficulty) to 3 (unable to do). The total score is obtained by summing 8 area scores and dividing by 8. The total HAQ-DI score ranges from 0 to 3 and corresponds to the current degree of disability:

    • 0 to < 1 Mild difficulties to moderate disability
    • 1 to < 2 Moderate disability
    • 2 to 3 Severe to very severe disability

  42. Health Assessment Questionnaire Disability Index (HAQ-DI) Response (MCID -0.22), Non-augmented

    Time frame: Week 48

    HAQ-DI response based on the MCID of -0.22 from baseline.

    The HAQ-DI is a questionnaire validated for RA self-assessment by subjects that contains 20 questions in the following 8 functional areas:

    • Dressing and grooming
    • Arising
    • Eating
    • Walking
    • Hygiene
    • Reach
    • Grip
    • Common daily activities

    Scoring within each functional area is from 0 (without any difficulty) to 3 (unable to do). The total score is obtained by summing 8 area scores and dividing by 8. The total HAQ-DI score ranges from 0 to 3 and corresponds to the current degree of disability:

    • 0 to < 1 Mild difficulties to moderate disability
    • 1 to < 2 Moderate disability
    • 2 to 3 Severe to very severe disability

  43. the American College of Rheumatology (ACR) 20 Response, Subjects With 1 Prior b/tsDMARD

    Time frame: Week 12

    Response is defined as achieving at least 20% improvement from baseline to Week 12 in tender and swollen joint counts of 28 joints (scale 0=best to 28=worst) and 3 out of the following 5 measures: Health Assessment Questionnaire Disability Index (HAQ-DI) score (scale 0=no difficulty to 3=unable to do), subject global assessment (0=best to 10=worst), subject pain (0=no pain to 10=worst), evaluator's global assessment (0=best to 10=worst), or high sensitivity C-reactive protein (hsCRP) concentration (mg/L).

  44. the American College of Rheumatology (ACR) 20 Response, Subjects With 2 Prior b/tsDMARD

    Time frame: Week 12

    Response is defined as achieving at least 20% improvement from baseline to Week 12 in tender and swollen joint counts of 28 joints (scale 0=best to 28=worst) and 3 out of the following 5 measures: Health Assessment Questionnaire Disability Index (HAQ-DI) score (scale 0=no difficulty to 3=unable to do), subject global assessment (0=best to 10=worst), subject pain (0=no pain to 10=worst), evaluator's global assessment (0=best to 10=worst), or high sensitivity C-reactive protein (hsCRP) concentration (mg/L).

  45. the American College of Rheumatology (ACR) 20 Response, Subjects With 3 Prior b/tsDMARD

    Time frame: Week 12

    Response is defined as achieving at least 20% improvement from baseline to Week 12 in tender and swollen joint counts of 28 joints (scale 0=best to 28=worst) and 3 out of the following 5 measures: Health Assessment Questionnaire Disability Index (HAQ-DI) score (scale 0=no difficulty to 3=unable to do), subject global assessment (0=best to 10=worst), subject pain (0=no pain to 10=worst), evaluator's global assessment (0=best to 10=worst), or high sensitivity C-reactive protein (hsCRP) concentration (mg/L).

  46. the American College of Rheumatology (ACR) 20 Response, Subjects With >=4 Prior b/tsDMARD

    Time frame: Week 12

    Response is defined as achieving at least 20% improvement from baseline to Week 12 in tender and swollen joint counts of 28 joints (scale 0=best to 28=worst) and 3 out of the following 5 measures: Health Assessment Questionnaire Disability Index (HAQ-DI) score (scale 0=no difficulty to 3=unable to do), subject global assessment (0=best to 10=worst), subject pain (0=no pain to 10=worst), evaluator's global assessment (0=best to 10=worst), or high sensitivity C-reactive protein (hsCRP) concentration (mg/L).

Sponsors and collaborators

Lead sponsor

SetPoint Medical Corporation

Industry

Registry information

Official study title

Vagus Nerve Stimulation Using the SetPoint System for Moderate to Severe Rheumatoid Arthritis: The RESET-RA Study

Acronym: RESET-RA

Important dates

Study start
2021
Primary completion
2024
Study completion
2027
First posted
Sep 7, 2020
Registry last updated
Apr 14, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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