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NCT Number: NCT05423587

Genicular Artery Embolisation for Knee Osteoarthritis II

This clinical study is designed as a double-blind sham controlled randomised trial with the option of sham group crossover to receive the GAE treatment at 6 months after unblinding. This study will determine if embolisation of abnormal neovasculature arising from branches of the genicular arteries reduces pain in patients with knee osteoarthritis. The study patient population will consist of up to 110 subjects with knee pain for at least 3 months that is resistant to conservative treatment measures. Subjects will be treated with knee embolisation or 2 mL of saline in the sham arm. At 6 months, all subjects in the sham arm will be allowed to cross-over and receive the embolisation procedure with a follow-up duration of 18 months. The total planned study duration is 3.5 years.

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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

Primary location

Royal Berkshire NHS Foundation Trust

Reading, RG1 5AN, United Kingdom

Location status: Recruiting

Location contact

Mark W Little, MD

CONTACT

[email protected]

01183225111

About this study

This is a single-center, randomised trial to compare patients who receive genicular artery embolisation of the knee with patients who receive a sham procedure with saline injection.

The study population will consist of up to 110 subjects with knee pain that is resistant to conservative treatment measures for at least 3 months. Subjects will be followed for 24 months. At 6 months patients will be unblinded and offered an optional crossover to receive the GAE procedure with 18 months follow-up.

Alongside a sham surgery placebo arm, a high-quality systematic review of surgical RCTs was used as a suitable benchmark to inform the sample size and power calculation.

With a 0-100 scale for the primary endpoint of KOOS4, assuming a 1:1 randomization, a mean difference of 6.4 (i.e., effect size) between GAE and Sham treatments, a common standard deviation of 10 (i.e., a Cohen's D of 0.64), an alpha error of 2-sided 0.05 and a power of 0.85, the 2-arm total sample size the requirement is 88 subjects (44 each arm) by Normal approximation. Allowing for a participant dropout rate of 20%, the enrolment goal is 110 participants, approximately 55 in each study arm.

All study subjects will undergo a physical exam and history, a contrast-enhanced knee MRI, blood serum and neuropschological assessment with a functional head MRI to identify potential predictors of treatment success.

In the GAE treatment arm subject will undergo a genicular artery embolization with Embozene microspheres (100 micron) (Varian Medical Systems) and the Sham group will receive saline through the transarterial catheter through groin access.

Participants will be randomly assigned to have particulate embolisation with 100-micron Embozene particles, or to injection with 2 ml heparinized normal saline (sham arm) At 6 months participants will be unblinded and there will be an open extension period for 6 months, in which participants in the sham arm will be offered GAE.

Follow-up visits will be at 1 month, 3 months, 6 months, 12 months and 24 months post randomisation. At these visits subjects will complete the KOOS score, the visual analog scale (VAS) pain score, an analgesia diary, and at specific time points the EQ-5D-3L, and report any new adverse events (AEs).All subjects will undergo a contrast-enhanced knee MRI at baseline and at 6 and 12 months.

At 6 months after unblinding the sham group subjects have the option to cross over and receive the GAE treatment with follow-up at 1 month, 3 months, 6 months, 12 months and 18 months.

Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

ALL inclusion criteria below need to be fulfilled for the patient to participate in the study.

  • Participant is willing and able to give informed consent for participation in the study.
  • Participants aged 45 years or above.
  • Grade 1-3 knee OA on X-ray as per Kellgren-Lawrence Grading Scale
  • Knee pain for at least 3 months resistant to conservative non-surgical treatment (e.g., physiotherapy, steroid injections, weight loss programs, PRP (platelet-rich plasma) injections)
  • Be able to lie flat for at least 6 hours-this will be assessed by asking how participants sleep (bed, chair recumbent, semi-recumbent) and assessing what prevents them from lying flat overnight (breathlessness, back pain, etc)
  • Minimum score of 50 on baseline 0 - 100 VAS

Exclusion criteria

The patient may not enter the study if ANY of the following apply:

  • Rheumatoid arthritis or infectious arthritis
  • Severe knee OA (grade 4 on x-ray as per Kellgren-Lawrence Grade)
  • Renal impairment: eGFR <45. Assessed from medical records or a blood test if required as is part of standard clinical practice when considering a patient for a therapeutic intervention.
  • Patients with a bleeding diathesis, or other bleeding risk such as patients on warfarin which cannot be stopped easily (e.g., patients with metallic heart valves) assessed by asking the patient and from medical records. Uncorrectable bleeding diathesis: INR>1.6, Platelets <50,000
  • Requires oxygen on ambulation. Assessed by asking the patient and from medical records.
  • Low life expectancy (<1 year)
  • Communication difficulty due to language barriers
  • Contraindication to MRI
  • Known allergies to barium sulfate, 3-aminopropyltrialkoxysilane, polyphosphazene or IV radiopaque contrast agent
  • History of Peripheral Arterial Disease (PAD) with intermittent claudication and/or rest pain
  • Pregnancy or positive pregnancy test (the participant will be exposed to ionising radiation during the fluoroscopy procedure)
  • Any other significant disease or disorder which, in the opinion of the recruiting physician, may put the participants at risk because of participation in the study, or may influence the result of the study or the participant's ability to participate

Treatment and study plan

Genicular Artery Embolisation

Procedure

Transarterial catheter directed embolisation of hypervascularity in patients with mild to moderate knee osteoarthritis

Other names: Embozene Microspheres, Embozene

Genicular Artery Injection

Procedure

Transarterial catheter directed injection of normal (0.9%) saline in patients with mild to moderate knee osteoarthritis

Primary outcomes

  1. Determine if embolisation of abnormal neovasculature arising from branches of the genicular arteries reduces pain in patients with knee OA compared to Sham treatment

    Time frame: 6 months

    Change from baseline to 6 months post randomisation in the mean score on four Knee Injury and Osteoarthritis Outcome Score subscales, covering pain, symptoms, activities of daily living, and quality of life (KOOS4); scores range from 0 (worst) to 100 (best)

Secondary outcomes

  1. Determine clinical success

    Time frame: 6 months

    The proportion of subjects reporting at least a 10- point improvement in KOOS scores at 6-months (where a 10-point change from baseline is defined as the minimum clinically important difference (MCID)

  2. Assessment of pain relief

    Time frame: 6 months

    Pain relief at 6 months post randomisation, using the patient-reported 0 - 100 visual analogue scale (VAS) pain score

  3. Determine if embolisation improves pain, function, and quality of life in patients with knee OA compared to Sham treatment

    Time frame: 6 months

    All 5 subscales of the KOOS questionnaire will be analysed at 6 months post randomisation.

Other outcomes

  1. Determine safety and toxicity

    Time frame: 6 months follow-up

    Proportion of subjects experiencing relevant adverse events (as per SIR Adverse Event Classification System) at 6 months post randomisation

  2. Determine if improvement of knee osteoarthritis can be described by imaging analysis following GAE vs Sham

    Time frame: 6 months

    Whole Organ Magnetic Resonance Imaging Score (WORMS) for non-invasive assessment of synovial hypertrophy and neo-vascularization for osteoarthritis at 6 months post randomisation.

  3. Quantification of a personalised psychometric pain profile to determine whether treatment response can be predicted using behavioural indicators of predisposition to central facilitation of pain

    Time frame: 6 months

    Pain Catastrophizing Scale (PCS) patient questionnaire: Score reflects on painful experiences of the patient. Score from 0 (minimum) to 52 (maximum). A higher score means worse outcome

  4. Determine quality of life changes

    Time frame: 6 months

    Changes in quality of life measured by Euro-Quality of Life-5D-3L (EQ-5D-3L) assessing five dimensions (mobility, self-care, usual activities, pain/discomfort and anxiety/depression), each having three levels (3L): no problems, some problems, extreme problems (labelled 1-3) in a descriptive fashion.

  5. Assess patient reported acceptability of study treatment

    Time frame: 1 week after treatment

    The PROM questionnaire (Patient reported outcome measures) (10 question patient questionnaire) reports scores between 9 (minimum) to 90 (maximum) where a high score is considered worse acceptance (worse outcome)

  6. Determine if patient's need for analgesia will be reduced

    Time frame: 6 months

    Change of analgesia intake at 6 months post randomisation.

  7. Assess durability of GAE

    Time frame: 24 months

    Time to failure, i.e., time to next invasive intervention for those receiving GAE treatment following (a) randomisation, or (b) crossing over to GAE from Sham arm.

  8. Perform a health economic cost effectiveness analysis of GAE versus other treatment modalities in the moderate knee OA space

    Time frame: 6 months

    Changes in quality of life measured by EuroQoL-5D (EQ-5D-3L) combined with the time assessment to failure (durability of GAE), i.e., time to next invasive intervention for those receiving GAE treatment following (a) randomization, or (b) crossing over to GAE from Sham arm will be assessed together to describe the cost effectiveness.

  9. Determine if embolisation improves pain, function, and quality of life in patients with knee OA in the treatment group

    Time frame: 24 months follow-up

    All 5 subscales of the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire will be analysed at 12 and 24 months post randomisation. Scores range from 0 (minimum, worst) to 100 (maximum, best).

  10. Determine quality of life changes in the GAE group at 12 and 24 months

    Time frame: 24 months follow-up

    Changes in quality of life measured by Euro-Quality of Life-5D-3L (EQ-5D-3L) assessing five dimensions (mobility, self-care, usual activities, pain/discomfort and anxiety/depression, each having three levels (3L): no problems, some problems, extreme problems (labelled 1-3) at 12 and 24 months post randomisation in a descriptive fashion.

  11. Describe imaging outcomes of knee at 12 months in GAE

    Time frame: 12 months

    Whole Organ Magnetic Resonance Imaging Score (WORMS) for non-invasive assessment of synovial hypertrophy and neo-vascularization for osteoarthritis will be evaluated in the GAE group at 12 months post randomisation.

  12. Determine if patient's need for analgesia will be reduced in the GAE group

    Time frame: 24 months

    Change of analgesia intake at 12 and 24 months post randomisation.

  13. Assessment of pain relief in the GAE group

    Time frame: 24 months

    Pain relief at 12 and 24 months post randomisation, using the patient-reported 0 - 100 visual analogue scale (VAS) pain score

  14. Determine if embolisation improves pain, function, and quality of life in patients with knee OA in the treatment group and compare with the Sham group in subjects who do not cross over at 12 and 24 months

    Time frame: 24 Months

    All 5 subscales of the Knee Injury and Osteoarthritis Outcome Score (KOOS) will be analysed at 12 and 24 months post randomisation in the GAE and Sham group. Scores range from 0 (worst) to 100 (best).

  15. Determine quality of life changes in the GAE and sham group

    Time frame: 24 months

    The second part of the Euro-Quality of Life-5D-3L questionnaire consists of a visual analytic scale (VAS) on which the patient rates his / her perceived health from 0 (the worst imaginable health) to 100 (the best imaginable health) at 12 and 24 months post randomisation in the GAE group and compare with the Sham group in subjects who do not cross over.

  16. Determine if patient's need for analgesia will be reduced

    Time frame: 24 months

    Compare changes of analgesia intake at 12 and 24 months post randomisation in the GAE group with the Sham group in subjects who do not cross over.

  17. Assessment of pain relief

    Time frame: 24 months

    Compare pain relief in the GAE group at 12 and 24 months post randomisation, using the patient-reported 0 - 100 visual analogue scale (VAS) pain score, and compare to the Sham group in subjects who do not cross over.

  18. Determine if embolisation improves pain, function, and quality of life in patients with knee OA in the Sham crossover group at 1, 3, 6, 12 and 18 months

    Time frame: 18 months

    All 5 subscales of the Knee Injury and Osteoarthritis Outcome Score (KOOS) will be analysed at 1,3,6, 12 and 18 months post treatment in the Sham crossover group. Scores range from 0 (worst) to 100 (best).

  19. Assessment of pain relief in the Sham crossover group

    Time frame: 18 months

    Pain relief at 1,3,6,12 and 18 months post treatment in the Sham crossover group, using the patient-reported 0 - 100 visual analogue scale (VAS) pain score

  20. Determine if patient's need for analgesia will be reduced in the Sham crossover group

    Time frame: 18 months

    Change of analgesia intake at 1,3,6,12 and 18 months post treatment in the Sham crossover group.

  21. Determine quality of life changes in the Sham crossover group

    Time frame: 18 months

    Changes in quality of life measured by Euro-Quality of Life-5D-3L (EQ-5D-3L) assessing five dimensions (mobility, self-care, usual activities, pain/discomfort and anxiety/depression, each having three levels (3L): no problems, some problems, extreme problems (labelled 1-3) at 6, 12 and 18 months post treatment in a descriptive fashion.

  22. Determine if improvement of knee osteoarthritis can be described by imaging analysis in the Sham crossover group following GAE

    Time frame: 12 months

    Whole Organ Magnetic Resonance Imaging Score (WORMS) for non-invasive assessment of synovial hypertrophy and neo-vascularization for osteoarthritis at 6 and 12 months post treatment in the Sham crossover group

  23. Quantification of mindfulness as part of a personalised psychometric pain profile to determine whether treatment response can be predicted using behavioural indicators of predisposition to central facilitation of pain

    Time frame: 6 months

    Five-Facet Mindfulness Patient Questionnaire (FFMQ): Reporting a score between 15 (minimum) and 75 (maximum). Higher scores are better and indicative of high trait mindfulness.

  24. Assessment of depressive symptoms as part of a personalised psychometric profile

    Time frame: 6 months

    Patient Health Questionnaire (PHQ-9): Reports a score between 0 (minimum) and 27 (maximum) with higher scores being worse representing high depressive symptoms

  25. Assessment of patient's psychological flexibility as part of personalised psychometric profile

    Time frame: 6 months

    Pain Interference - Short Form 6b (PROMIS) patient questionnaire: Reports a score between 6 (minimum) and 30 (maximum), with higher scores being worse representing high pain interference

  26. Assessment of a patient's anxiety as part of a personalised psychometric profile

    Time frame: 6 months

    Generalized Anxiety Disorder (GAD-7) patient questionnaire: reports a score between 0 (minimum) and 21 (maximum). Higher scores are worse representing more severe levels of anxiety.

  27. Quantification of patient's psychological flexibility as part of a personalised psychometric profile

    Time frame: 6 months

    Committed Action Questionnaire (CAQ-8): Reports a score between 0 (minimum) and 48 (maximum). Higher scores mean better outcome representing high commitment to goals.

  28. Quantification of a patient's intolerance of uncertainty

    Time frame: 6 months

    Intolerance of Uncertainty Scale - Short Form patient questionnaire: Reports a score between 0 (minimum) and 60 (maximum). Higher scores are worse representing high intolerance of uncertainty.

  29. Quantification of a patient's sleep quality as part of personalised psychometric profile

    Time frame: 6 months

    Pittsburgh Sleep Quality Index (PSQI) patient questionnaire: Reports a score between 0 (minimum) to 21 (maximum). Higher scores are worse indicating worse sleep quality.

  30. Assessment of psychological inflexibility in pain as part of a personalised psychometric pain profile to determine whether treatment response can be predicted using behavioural indicators of predisposition to central facilitation of pain

    Time frame: 6 months

    Psychological Inflexibility in Pain Scale (PIPS) patient questionnaire: reports scores between 16 (minimum) to 112 (maximum). Higher scores (worse results) indicate low flexibility in regard to dealing with pain.

  31. Quantification of the perspective of a participant's viewpoint on pain as part of a personalised psychometric pain profile

    Time frame: 6 months

    Pain Priors Questionnaire

  32. Behavioural quantification of psychological flexibility to stratify patients who achieve optimal clinical outcomes from the treatment procedure.

    Time frame: 6 months

    Wisconsin Card Sorting Task: reports reaction time measured in milliseconds (lower value is better outcome as better cognitive function)

  33. Assess functional connectivity between brain regions and investigate the influence of metabolite levels within pain modulatory regions as a neurochemical marker for vulnerability to further chronic pain states.

    Time frame: 6 months

    Functional head MRI

  34. Assess patient's capacity of central pain modulation

    Time frame: 6 months

    Quantitative sensory testing: Central pain modulation (CPM) measures the degree to which pain at one site inhibits pain at a distal site. The difference between the initial and final rating is taken as a score of the participant's CPM capacity with a range of -10 to 10 with -10 representing a better result with high pain inhibition/modulation.

  35. Assess patient's intrinsic attention to pain

    Time frame: 6 months

    Intrinsic Attention to Pain (IAP) test measures whether a participant's attention is intrinsically gravitated towards, or away from pain during thermal stimulation with a score range of +2 to -2, with + 2 representing worse results indicating an inability to attentionally disengage from pain.

  36. Assess patient's capacity of central facilitation of pain

    Time frame: 6 months

    Temporal Summation (TS) test: describes the degree to which pain responses are centrally enhanced by rapid repeated presentation. A score between -10 to 10 is reported with 10 representing high pain summation as a worse result and -10 no pain summation.

  37. Perception of health by patient in the GAE and sham group

    Time frame: 6 months

    The second part of the Euro-Quality of Life-5D-3L questionnaire consists of a visual analytic scale (VAS) on which the patient rates his / her perceived health from 0 (the worst imaginable health) to 100 (the best imaginable health).

  38. Perception of health by patient in the GAE group

    Time frame: 24 months follow-up

    The second part of the Euro-Quality of Life-5D-3L questionnaire consists of a visual analytic scale (VAS) on which the patient rates his / her perceived health from 0 (the worst imaginable health) to 100 (the best imaginable health).

  39. Perception of health by patient in GAE and sham group at 12 and 24 months

    Time frame: 24 months

    The second part of the Euro-Quality of Life-5D-3L questionnaire consists of a visual analytic scale (VAS) on which the patient rates his / her perceived health from 0 (the worst imaginable health) to 100 (the best imaginable health) at 12 and 24 months post randomisation in the GAE group and compare with the Sham group in subjects who do not cross over.

  40. Perception of health by patient in sham crossover group at 6, 12 and 18 months

    Time frame: 18 months

    The second part of the Euro-Quality of Life-5D-3L questionnaire consists of a visual analytic scale (VAS) on which the patient rates his / her perceived health from 0 (the worst imaginable health) to 100 (the best imaginable health) at 6, 12 and 18 months post treatment.

Study contacts

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

Heike S Hausen, MD

CONTACT

[email protected]

2068903102

Kate Pietrovito

CONTACT

[email protected]

+19782908408

Sponsors and collaborators

Lead sponsor

Varian, a Siemens Healthineers Company

Industry

Registry information

Official study title

Genicular artEry embolisatioN in patiEnts With oSteoarthrItiS of the Knee II

Acronym: GENESISII

Important dates

Study start
2022
Primary completion
2027
Study completion
2028
First posted
Jun 21, 2022
Registry last updated
Dec 3, 2024

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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