An interventional study of Peripheral Electrical Stimulation (PES) and Paired Pulse Electrical Stimulation (ppES) in Knee Osteoarthristis, Knee Pain Arthritis and Knee Pain Chronic, sponsored by Northeastern University. Not yet recruiting. Open to participants aged 45 Years and older. Per ClinicalTrials.gov, last updated 2026-09-22.
Sponsored by Northeastern University · Not applicable, Interventional, and Treatment
Knee osteoarthritis is a leading cause of disability, and the muscle weakness that limits walking in this population arises not only from the joint itself but from afferent signals that inhibit motor drive to the thigh muscle, which is why exercise alone so often produces incomplete recovery. This project examines whether brief, non-invasive electrical stimulation of a nerve behind the knee can reduce inhibition and restore muscle coordination while walking in adults with knee osteoarthritis. Establishing this effect would identify a modifiable neural target that current rehabilitation does not address, with the potential to improve physical function and independence for the millions of adults living with this condition.
Knee osteoarthritis affects more than 14 million adults in the United States and is a leading cause of disability. Its most disabling consequence is not joint degeneration alone but persistent quadriceps dysfunction. Afferent signals arising from the painful joint inhibit the descending motor drive that activates the muscle, so voluntary activation remains incomplete. Exercise therapy, the mainstay of care, therefore produces strength gains of only 10 to 20 percent against the 30 to 40 percent required for meaningful clinical benefit, and patients walk with rigid, co-contracted movement patterns that concentrate joint loading and accelerate degeneration. Existing interventions address either pain or motor retraining; none target the cortical circuits in which the two interact. This study tests whether paired-pulse electrical stimulation (ppES) of the tibial nerve can reduce that inhibition. ppES delivers two stimuli in rapid succession: the first activates sensory afferents projecting to the primary somatosensory cortex, and the second, delivered at a precisely timed interval, induces heterosynaptic depression of that transmission, in turn reducing sensory-driven inhibition of motor output. Applied at the tibial nerve, ppES acts on the sensorimotor integration that governs quadriceps activation during walking. Twenty adults with knee osteoarthritis will each complete two single-session visits separated by at least seven days, receiving active ppES at one visit and sham stimulation at the other in randomized order, with participants and outcome assessors blinded. At each visit, before intervention and again immediately and 30 minutes afterward, we will measure short-latency afferent inhibition of the quadriceps motor pathway and quadriceps-hamstrings co-contraction during treadmill walking, the two primary outcomes. Somatosensory evoked potentials and modular organization of gait will be measured as secondary outcomes. Aim 1 will determine whether ppES reduces sensorimotor inhibition and co-contraction relative to sham. Aim 2 will determine whether baseline pain sensitization, cortical sensory processing, and sensorimotor inhibition predict the magnitude and variability of individual response. Establishing that this circuit is modifiable would identify a rehabilitation target that current care does not address and would provide the mechanistic evidence and effect-size estimates required for a trial of ppES as an adjunct to exercise.
10,054 studies on the registry are indexed under Pain; 1,649 are open to participants now.
This study's planned enrollment of 50 is below the median of 66 across 8,493 interventional studies indexed under Pain.
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Unilateral or bilateral knee OA, per NICE criteria
Exclusion Criteria:
Current Use of prescription and over the counter medications will be grounds for exclusion except for:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Other: Paired Pulse Electrical Stimulation (ppES)
Other: Peripheral Electrical Stimulation (PES)
Participants will receive a single session intervention of single pulses of electrical stimulation to the tibial nerve at a below motor threshold intensity. These pulses will be delivered with a pulse width of 1000 microseconds, delivered at 20 Hz frequency. This intervention will last approximately 30 minutes and deliver 24,000 stimulation pulses.
Participants will receive a single session intervention of pairs of electrical stimulation pulses delivered to the tibial nerve. These pairs will use pulses of 1000 microseconds duration, separated by a 5 millisecond interstimulus interval, delivered at a frequency of 10Hz. Participants will receive 12,000 stimulation pairs during an intervention lasting approximately 30 minutes.
Change in Short-latency Afferent Inhibition Ratio
Measuring change in short-latency afferent inhibition (SAI) ratio of the motor cortex controlling quadriceps muscle excitability across timepoints
Time frame: Before, immediately after, and 30 minutes after intervention at each study session
Change in Muscle Co-Activation Percentage During Treadmill Walking
Measuring change in co-activation percentage of quadriceps and hamstring muscle pairs during treadmill walking across timepoints
Time frame: Before, immediately after, and 30 minutes after intervention at each study session
Change in Somatosensory Evoked Potentials Amplitude
Measuring change in somatosensory evoked potentials (SEPs) amplitude measured in the sensory cortex in response to peripheral electrical stimulation across timepoints
Time frame: Before, immediately after, and 30 minutes after intervention at each study session
Change in Dynamic Motor Control Index of Gait During Treadmill Walking
Measuring change in the organization of motor control strategies, in terms of dynamic motor control index, during treadmill walking across timepoints
Time frame: Before, immediately after, and 30 minutes after intervention at each study session
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