Osteoarthritis, Knee
Conditions
Keywords
acupuncture, osteoarthritis, fMRI
Brief summary
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.
Interventions
DEVICEacupuncture
patient will receive high dose, low dose or sham acupuncture treatment.
Sponsors
National Center for Complementary and Integrative Health (NCCIH)
Beth Israel Deaconess Medical Center
Brigham and Women's Hospital
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
40 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Volunteers 40-70 years of age. 2. 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. 3. Radiographic evidence of Grade 2 or 3 knee OA using the Kellgren-Lawrence Scale \[78, 85-87\]. 4. 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. 5. 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
1. Any interventional procedure for knee pain, including corticosteroid injections (within 6 months, \[88\]) to the knee. 2. 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. 3. The intent to undergo surgery during the time of involvement in the study. 4. 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. 5. 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. 6. Non-ambulatory status. 7. 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. 8. Presence of any contraindications to fMRI scanning. For example: cardiac pacemaker, metal implants, fear of closed spaces, pregnancy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Knee Injury and Osteoarthritis Outcome Score (KOOS Pain Rating) at 5-7 Weeks Post-Treatment | One post-treatment measurement 5-7 weeks after baseline | 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. |
| Cortical Thickness Changes at 5-7 Weeks Post-Treatment | 2 days; one at baseline and another post-treatment measurement taken 5-7 weeks after baseline | 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. |
Countries
United States
Participant flow
Recruitment details
Forty-four acupuncture naïve patients aged 43-70 with a diagnosis of chronic osteoarthritis in the right and/or left knee participated in the study. 30 (13 females) completed all study procedures. Fourteen subjects did not complete the study. All subjects were recruited form the Boston area over the course of the past 3 years.
Pre-assignment details
Fourteen subjects did not complete the study due to problems with scheduling (6), ineligibility at screening (3), disinterest (2), claustrophobia (1), or inability to adhere to study requirements in scanner (2). Of the 14 subjects who dropped, four dropped out after randomization.
Participants by arm
| Arm | Count |
|---|---|
| High Dose Acupuncture six needle applied during acupuncture
acupuncture : patient will receive high dose, low dose or sham acupuncture treatment. | 15 |
| Low Dose Acupuncture two needles will be applied.
acupuncture : patient will receive high dose, low dose or sham acupuncture treatment. | 15 |
| Placebo Acupuncture sham acupuncture treatment will be applied
acupuncture : patient will receive high dose, low dose or sham acupuncture treatment. | 14 |
| Total | 44 |
Baseline characteristics
| Characteristic | Low Dose Acupuncture | Placebo Acupuncture | High Dose Acupuncture | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 14 Participants | 15 Participants | 44 Participants |
| Age, Continuous | 58 years STANDARD_DEVIATION 8 | 54 years STANDARD_DEVIATION 7 | 60 years STANDARD_DEVIATION 9 | 58 years STANDARD_DEVIATION 8 |
| Region of Enrollment United States | 15 participants | 14 participants | 15 participants | 44 participants |
| Sex: Female, Male Female | 8 Participants | 4 Participants | 5 Participants | 17 Participants |
| Sex: Female, Male Male | 7 Participants | 10 Participants | 10 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 15 | 0 / 15 | 0 / 14 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 | 0 / 14 |
Outcome results
Primary
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.
Time frame: 2 days; one at baseline and another post-treatment measurement taken 5-7 weeks after baseline
Population: We combined low and high dose acupuncture into one group because we found there were not clinical differences between the two group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Dose Acupuncture | Cortical Thickness Changes at 5-7 Weeks Post-Treatment | 2.9 millimeters | Standard Deviation 0.15 |
| Low Dose Acupuncture | Cortical Thickness Changes at 5-7 Weeks Post-Treatment | 3.13 millimeters | Standard Deviation 0.28 |
Primary
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.
Time frame: One post-treatment measurement 5-7 weeks after baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Dose Acupuncture | Knee Injury and Osteoarthritis Outcome Score (KOOS Pain Rating) at 5-7 Weeks Post-Treatment | 59 units on KOOS scale | Standard Deviation 13 |
| Low Dose Acupuncture | Knee Injury and Osteoarthritis Outcome Score (KOOS Pain Rating) at 5-7 Weeks Post-Treatment | 53 units on KOOS scale | Standard Deviation 9 |
| Placebo Acupuncture | Knee Injury and Osteoarthritis Outcome Score (KOOS Pain Rating) at 5-7 Weeks Post-Treatment | 56 units on KOOS scale | Standard Deviation 19 |