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NCT Number: NCT07832682

Neurofeedback for Pain Sensitization in Knee Osteoarthritis

The goal of this clinical trial is to learn whether a training method called neurofeedback is safe and practical to use in people with knee osteoarthritis (knee OA). Neurofeedback uses a computer screen to show people their body's responses as they happen, so they can learn to change those responses. The response being trained in this study is a protective reflex in the leg. This reflex is often stronger than normal in people with knee OA, which may be a sign that their nervous system has become more sensitive to pain.

The main questions this study aims to answer are:

1. Is this training safe, and what side effects do people have? 2. Can people with knee OA complete the training, and do they find it acceptable?

Researchers will compare people who receive real neurofeedback training with people who receive a placebo (inactive) version of the training. In the placebo version, the electrical pulses are too weak to trigger the reflex, and what appears on the screen is not based on the person's own reflex. Comparing the two groups helps researchers tell which parts of taking part are difficult because of the study set-up itself and which are difficult because of the training.

Participants will:

* Visit a research laboratory at Northeastern University in Boston 7 times: one measurement visit lasting about 3 hours, then 6 training visits lasting about 60 to 90 minutes each. Training visits happen about twice a week, with at least 2 days between visits. * At the measurement visit, have small sensors placed on the head and legs, receive brief electrical pulses to the leg and brief magnetic pulses to the head, and have their sensitivity to pain checked using brief pressure on the kneecaps and wrist. * At each training visit, receive brief electrical pulses to the leg while watching a screen. People in the neurofeedback group will try to make a bar on the screen smaller. People in the placebo group will watch a screen that does not reflect their own reflex. * Answer questionnaires about their knee pain and daily activities. * Receive a phone call and complete a short online survey about 2 weeks after the last training visit.

A smaller group of participants will take part in the measurement visit only. They may not receive neurofeedback or placebo training.

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Key information

Conditions

Knee Osteoarthritis Arthritis Joint Diseases Musculoskeletal Diseases Osteoarthritis Osteoarthritis, Knee Rheumatic Diseases

Age range

45 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

  • Age 45 years or older
  • Symptomatic knee osteoarthritis meeting the clinical definition in the National Institute for Health and Care Excellence (NICE) guidelines: knee pain for more than 3 months and morning stiffness lasting less than 30 minutes
  • Able to speak and understand English
  • Able to attend all study visits at the study site in Boston, MA

Exclusion criteria

Stimulation safety

  • Pacemaker, implanted defibrillator, or other implanted electronic device
  • Metal implants in the head
  • Implants in the lower limb, including prior knee arthroplasty
  • History of seizures or epilepsy
  • Prior adverse reaction to transcranial magnetic stimulation
  • Frequent or severe headaches
  • Suspected or diagnosed cardiac disease
  • Pregnancy (self-reported)

Neurological, psychiatric, and medical

  • Neurological disease, including multiple sclerosis
  • Currently active major depressive disorder, defined as a current clinical diagnosis of major depressive disorder or ongoing treatment for depression; a prior history that is neither active nor treated is not exclusionary
  • Insulin-dependent diabetes
  • Raynaud's phenomenon, cold urticaria, or other cold-induced reaction
  • Large ischaemic scars

Pain and musculoskeletal

  • Lower extremity pain other than knee osteoarthritis

Skin and sensation at stimulation sites

  • Altered skin sensation of the thigh
  • Swollen, infected, inflamed, or damaged skin of the thigh

Substances

  • Use of medication known to alter pain perception or cortical excitability, including opioids, gabapentinoids, antidepressants (SSRIs, SNRIs, tricyclics), benzodiazepines, anti-seizure medications, muscle relaxants, prescription sleep medications, and cannabis or cannabinoids
  • Use of alcohol or recreational drugs within 12 hours before a study visit

Radiographic confirmation is not required, consistent with current clinical recommendations for knee osteoarthritis diagnosis. Commonly used medications that do not alter pain perception or cortical excitability are permitted and recorded as covariates.

Treatment and study plan

FWR Down-Conditioning Neurofeedback

Other

Participants receive trial-by-trial feedback of flexor withdrawal reflex amplitude.

Sham Feedback

Other

Participants receive sham trial-by-trial feedback of flexor withdrawal reflex amplitude. The placebo condition is matched on instrumentation, session structure, stimulation triggering, and visit burden, and differs in stimulation intensity and in whether displayed feedback derives from the participant's own reflex.

Primary outcomes

  1. Incidence of adverse events

    Time frame: Enrollment through 14 days after the final intervention session (approximately 6 weeks)

    Number of participants with at least one adverse event and total event count, characterized by nature, severity, relationship to study procedures, and timing. Serious adverse events reported separately.

  2. Number of participants completing the intervention protocol

    Time frame: Randomization through final intervention session (approximately 4 weeks)

    Participants completing all 6 intervention sessions, as a proportion of those randomized. Reasons for discontinuation recorded.

  3. Percentage of scheduled intervention sessions attended

    Time frame: Intervention period (approximately 3 weeks)

    Sessions attended as a proportion of sessions scheduled, across all randomized participants.

  4. Adherence to the intervention protocol

    Time frame: Intervention period (approximately 3 weeks)

    Proportion of prescribed conditioning stimulations completed per session (225 across 3 blocks of 75), and sessions completed without protocol deviation.

  5. Participant-reported acceptability of the intervention

    Time frame: Week 2, Week 3, and Week 5

    Survey ratings of usefulness, ease of use, and burden, with identification of most and least helpful components and reasons for non-completion.

  6. Screening and enrollment yield

    Time frame: Duration of recruitment (approximately 30 months)

    Number screened, number eligible, number enrolled, and number declining, with reasons for ineligibility and declination.

Secondary outcomes

  1. Change in flexor withdrawal reflex amplitude

    Time frame: Week 1 through Week 3

    Rectified EMG reflex amplitude during conditioning blocks expressed relative to the within-session 25-stimulation baseline, and change across the 6 sessions.

  2. Pain severity

    Time frame: Week 1, Week 3, and Week 5

    Knee pain rated on a visual analog scale.

  3. Pressure pain threshold

    Time frame: Baseline (Day 1), then Week 1 through Week 3

    Algometry at the patellae and wrist.

  4. Temporal summation of pain

    Time frame: Baseline (Day 1)

    Change in pain rating across repeated weighted pinprick stimuli.

  5. Pain-related evoked potential (PREP) amplitude

    Time frame: Baseline (Day 1)

    Peak-to-peak amplitude of pain-related evoked potentials.

  6. Somatosensory-evoked potential (SSEP) amplitude

    Time frame: Baseline (Day 1)

    Peak-to-peak amplitude of somatosensory evoked potentials.

  7. Short-afferent inhibition

    Time frame: Baseline (Day 1)

    Conditioned motor evoked potential amplitude expressed relative to unconditioned response.

  8. Conditioned pain modulation

    Time frame: Baseline (Day 1)

    Change in pressure pain threshold during cold water immersion.

  9. Difference in pain intensity between experimentally evoked and real-world movement-evoked pain

    Time frame: Baseline (Day 1)

    VAS rating following the weight-bearing stimulation protocol minus rating following a participant-selected pain-provoking activity. Unit: mm on a 0-100 visual analog scale.

  10. Difference in WOMAC pain subscale score between experimentally evoked and real-world movement-evoked pain

    Time frame: Baseline (Day 1)

    VAS rating following the weight-bearing stimulation protocol minus rating following a participant-selected pain-provoking activity. Unit: units on a scale, 0-20

  11. Difference in SF-MPQ-2 total score between experimentally evoked and real-world movement-evoked pain

    Time frame: Baseline (Day 1)

    VAS rating following the weight-bearing stimulation protocol minus rating following a participant-selected pain-provoking activity. Unit: units on a scale 0-20.

  12. Change in KOOS Pain subscale score

    Time frame: Baseline (Day 1), Week 3, and Week 5

    Knee Injury and Osteoarthritis Outcome Score. Unit: units on a scale, 0-100, higher indicating fewer symptoms.

  13. Change in ICOAP total score

    Time frame: Baseline (Day 1), Week 3, and Week 5.

    Intermittent and Constant Osteoarthritis Pain. Unit: units on a scale, 0-100.

Study contacts

Contact information is provided by the study sponsor or research team.

David A Sherman, PhD

CONTACT

[email protected]

401-225-1233

Sponsors and collaborators

Lead sponsor

Northeastern University

Other

Collaborators

  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Registry information

Official study title

Targeting Pain Sensitization in Knee Osteoarthritis by Conditioning the Endogenous Pain Control System Using Reflex Conditioning.

Important dates

Study start
2026
Primary completion
2030
Study completion
2031
First posted
Sep 22, 2026
Registry last updated
Sep 22, 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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