An Acupuncture Functional Magnetic Resonance Imaging (fMRI) Study on Chronic Pain: Response Reliability and Dose Effect

Study Overview
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Brief Summary
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In this proposal, we plan to dynamically investigate brain response to verum acupuncture (of two different doses) and placebo acupuncture, using a paradigm that approximates clinical acupuncture practice across multiple treatment sessions in knee osteoarthritis (OA) patients. This proposal aims to: 1) characterize session-to-session brain responses to verum / sham acupuncture treatment (reliability of response) for OA patients, and 2) investigate how different doses of acupuncture influence brain response and acupuncture efficacy (impact of dose). The findings of this project will deepen our biological understanding on why and how acupuncture can treat chronic pain and what happens in the brain during the multiple-session acupuncture treatment.

Official Title
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An Acupuncture fMRI Study on Chronic Pain: Response Reliability and Dose Effect

Conditions
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Osteoarthritis, Knee

Intervention / Treatment
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* Device: acupuncture


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Volunteers 40-70 years of age. Meet the Classification Criteria of the American College of Rheumatology for osteoarthritis of the left / right knee for at least the past 3 months, as determined by the referring physician. Radiographic evidence of Grade 2 or 3 knee OA using the Kellgren-Lawrence Scale [78, 85-87]. Patients must have moderate or greater clinically significant pain on most days during the past month (more than 15 days out of 30, of average daily pain of >3/10) in the left or right knee. At least a 10th grade English-reading level; English can be a second language provided that the patients feel they understand all the questions used in the assessment measures. Exclusion Criteria: Any interventional procedure for knee pain, including corticosteroid injections (within 6 months, [88]) to the knee. Prior acupuncture treatment for any condition. Because we are using a placebo needle as a control, acupuncture-naive patients are necessary to maximize the benefits of blinding and to control expectancy. The intent to undergo surgery during the time of involvement in the study. Presence of any illness or medication use that is judged to interfere with the trial. For example: skin irritations around the knee such as psoriasis; bleeding disorders or anticoagulant use that would be contraindications for acupuncture; opioids or benzodiazepines, which may alter pain sensitivity and BOLD response. Knee pain due to other causes, such as inflammation or malignancy, other pain disorders that may refer pain to the leg, OA of ipsilateral hip, diagnosis of RA. Non-ambulatory status. History of cardiac, respiratory, or nervous system disease that, in the investigator's judgment, precludes participation in the study because of a heightened potential for adverse outcome. For example: asthma or claustrophobia. Presence of any contraindications to fMRI scanning. For example: cardiac pacemaker, metal implants, fear of closed spaces, pregnancy.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High dose acupuncture<br>six needle applied during acupuncture | Device: acupuncture<br>* patient will receive high dose, low dose or sham acupuncture treatment.<br>|
| Experimental: Low dose acupuncture<br>two needles will be applied. | Device: acupuncture<br>* patient will receive high dose, low dose or sham acupuncture treatment.<br>|
| Placebo Comparator: placebo acupuncture<br>sham acupuncture treatment will be applied | Device: acupuncture<br>* patient will receive high dose, low dose or sham acupuncture treatment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Knee Injury and Osteoarthritis Outcome Score (KOOS Pain Rating) at 5-7 Weeks Post-Treatment | The Knee injury and Osteoarthritis Outcome Score (KOOS) was used to measure clinical outcomes. KOOS is measured on a scale from 0-4 with 0 being no pain and 4 being extreme pain (the worst). The KOOS is comprised of 5 subscales, each of which produces an outcome score. These subscales include pain, other symptoms, function in daily living (ADL), function in sport and recreation, and knee-related quality of life (QOL). Based on previous studies, subscale scores of the KOOS related to pain, function in daily living, and function in sport and recreation were selected as the primary outcome of the present study. For each subscale, a normalized score was calculated, where 0 indicated the most extreme symptoms/pain and 100 indicated no symptoms/pain. | One post-treatment measurement 5-7 weeks after baseline | 
| Cortical Thickness Changes at 5-7 Weeks Post-Treatment | All eligible patients were scanned using fMRI while receiving treatment during acupuncture sessions 1, 3, and 6. Structural MRI data were only compared between Session 1 (pre-treatment) and Session 6 (post-treatment). The structural data was analyzed using FreeSurfer software. | 2 days; one at baseline and another post-treatment measurement taken 5-7 weeks after baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fMRI, acupuncture, osteoarthritis