Knee Osteoarthritis
Conditions
Keywords
flexor withdrawal reflex, nociceptive withdrawal reflex, reflex conditioning, operant conditioning, neurofeedback, pain sensitization, central sensitization, movement-evoked pain, quantitative sensory testing
Brief summary
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.
Interventions
OTHERFWR Down-Conditioning Neurofeedback
Participants receive trial-by-trial feedback of flexor withdrawal reflex amplitude.
OTHERSham Feedback
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.
Sponsors
Northeastern University
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
45 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of adverse events | 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. |
| Number of participants completing the intervention protocol | Randomization through final intervention session (approximately 4 weeks) | Participants completing all 6 intervention sessions, as a proportion of those randomized. Reasons for discontinuation recorded. |
| Percentage of scheduled intervention sessions attended | Intervention period (approximately 3 weeks) | Sessions attended as a proportion of sessions scheduled, across all randomized participants. |
| Adherence to the intervention protocol | 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. |
| Participant-reported acceptability of the intervention | 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. |
| Screening and enrollment yield | Duration of recruitment (approximately 30 months) | Number screened, number eligible, number enrolled, and number declining, with reasons for ineligibility and declination. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in flexor withdrawal reflex amplitude | 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. |
| Pain severity | Week 1, Week 3, and Week 5 | Knee pain rated on a visual analog scale. |
| Pressure pain threshold | Baseline (Day 1), then Week 1 through Week 3 | Algometry at the patellae and wrist. |
| Temporal summation of pain | Baseline (Day 1) | Change in pain rating across repeated weighted pinprick stimuli. |
| Pain-related evoked potential (PREP) amplitude | Baseline (Day 1) | Peak-to-peak amplitude of pain-related evoked potentials. |
| Somatosensory-evoked potential (SSEP) amplitude | Baseline (Day 1) | Peak-to-peak amplitude of somatosensory evoked potentials. |
| Short-afferent inhibition | Baseline (Day 1) | Conditioned motor evoked potential amplitude expressed relative to unconditioned response. |
| Conditioned pain modulation | Baseline (Day 1) | Change in pressure pain threshold during cold water immersion. |
| Difference in pain intensity between experimentally evoked and real-world movement-evoked pain | 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. |
| Difference in WOMAC pain subscale score between experimentally evoked and real-world movement-evoked pain | 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 |
| Difference in SF-MPQ-2 total score between experimentally evoked and real-world movement-evoked pain | 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. |
| Change in KOOS Pain subscale score | 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. |
| Change in ICOAP total score | Baseline (Day 1), Week 3, and Week 5. | Intermittent and Constant Osteoarthritis Pain. Unit: units on a scale, 0-100. |
Contacts
CONTACTDavid A Sherman, PhD
PRINCIPAL_INVESTIGATORDavid A Sherman, DPT
Northeastern University
Outcome results
None listed