Clinical trial NCT03877653: Freedom-1 Study for Chronic Knee Pain
Official title: Double-Blinded Randomized Control Trial of Knee Pain Utilizing Sub-Threshold Peripheral Nerve Stimulation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Osteoarthritic Knee Pain
Keywords: PNS
Chronic
Pain
Wireless
Neuromodulation
knee
osteoarthritic
peripheral nerve stimulation
infra patellar saphenous
Lead sponsor: Curonix LLC
Sponsor class: INDUSTRY
Collaborators: name: Texas Institute for Pain and spine
name: Performance Pain and Sports Medicine PLLC
name: Holy Cross Hospital, Inc
name: Colorado pain Care, LLC
name: Advanced Spine and Pain
name: Desert Orthopaedic Institute
name: Vista Clinical Research
name: Premier Pain Treatment
name: Florida Joint Pain Institute
name: Austin Orthopedic Institute
name: Kettering Health
First posted: 2019-03-18
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: placebo-controlled double blinded randomized clinical trial
Primary purpose: TREATMENT

Brief summary: To demonstrate the potential benefits and risk of active sub-threshold stimulation in the treatment of chronic knee pain as compared to subjects that did not have active stimulation. Improvement will be assessed in relation to the clinical outcome measures of pain, with primary endpoint; Pain relief rate as measured by the number of subjects with greater or equal to a 50% decrease in pain on the visual analog scale, comparing baseline to the 1-month follow-up.

Detailed description: Screening and Patient Selection Subjects will be selected from the pool patients of routine care who meet all the inclusion criteria for this study and none of the exclusion criteria, as described in Section 9.3.

Candidates will be given a patient information sheet (or Informed Consent) either in clinic or sent via post. Each approached candidate will be logged, assigned a screening number, and evaluated by the site research team. Subjects who sign the Informed Consent for participation and meet the Inclusion and Exclusion criteria will be enrolled and listed with an enrollment number. Recruitment will continue competitively until at least 84 subjects have evaluable data for evaluation of the primary endpoint.

Average pain levels will be captured at screening/baseline. Diagnostic Injection A diagnostic injection of the IPS under ultrasound, fluoroscopy or landmark guided in the clinic will be performed administering no more than 2cc of anesthetic. No steroids are allowed for the diagnostic injection. Only those subjects with significant temporary pain relief (\> 75%) compared to the average pain level captured at baseline, and after at least 2 hours of the injection, will be allowed to continue with the study.

Trial Implant All subjects will be brought to the procedure room or operating room (OR) for the trial implant procedure under local anesthetic. An introducer will be placed under ultrasound or fluoroscopic guidance at the target nerve and the electrodes percutaneously advanced towards the IPS. After insertion of the receiver and then confirmation of stimulation, the trial stimulator will be secured to the skin. The stimulator tail will be outside the body and attached to the skin. All subjects will undergo an active 7-day provisional test period. Only those subjects reporting \> 50% pain relief at the end of the 7-day provisional test period as compared to the average pain level captured at baseline will be allowed to continue with the study. The trial leads will be removed at the end of 7 days.

Permanent Implant All subjects responding to therapy with \> 50% pain relief at 7 days will, at a later date, be brought to the operating room (OR) and given a sedative and local anesthetic for implantation of a permanent electrode. An introducer will be placed under ultrasound or fluoroscopic guidance onto the target nerve and the electrode array advanced towards the nerve. The receiver will be mated with the electrode array, and, after confirmation of stimulation, the permanent stimulator will be tunneled and secured. The device will remain inactive for 10 days to allow for satisfactory healing. If no localized infection or other complication, subjects can be brought back to the office for randomization.

Randomization/Blinding Subjects will be randomized to either active sub-threshold (high frequency) stimulation or no stimulation (sham) by Curonix's Clinical Support. All subjects, the investigator and the research team will be blinded to the group assignment for up to 30 days from the moment of randomization.

Office Study Visits After randomization follow-up visits will be conducted at 1 week, 1 month, 3 months, and 6 months.

Initial and follow-up evaluations will consist of physical exams, pain scale (m-MPS), Knee Injury \& Osteoarthritis Outcome Score Junior (KOOS Jr), range of motion (flexion and extension measured by goniometer, work status and medication intake evaluation. At 1-month post-randomization, all subjects will be unblinded. Active devices can be adjusted for optimal pain relief. Sham devices will be reprogrammed to receive active treatment.

Available stimulation programs include tonic (on table testing), 500 Hz, 1000 Hz 1499 Hz frequency stimulation, all of which may be utilized on the same subject.

Remote Study Visits Follow up phone calls at 12 months, 18 months, and 24 months post-implantation will be performed to confirm durability of pain relief with the m-MPS and the global perceived effects scale (GPES). Any adverse events will be assessed and captured as part of the study.

Eligibility criteria: Inclusion Criteria:

i. Subject is over 18 years of age; ii. Subjects with a history of chronic, function-limiting (m-MPS \>6/10) knee pain from osteoarthritis of at least three months in duration with or without prior surgeries; iii. Subject has been diagnosed with Kellgren-Lawrence Grade II or III knee osteoarthritis, confirmed by X-ray studies conducted in the last year; iv. Subject has been examined and has been deemed to be an appropriate candidate for the procedure, including chronic knee pain in patients post total knee replacement (TKR); v. Subjects who are able to understand this investigation, and give voluntary, written informed consent to participate in this study; vi. Subjects who are able to co-operate with the study procedures and are willing to return to the center for all the required post-operative follow-ups; vii. Documented failure of at least two less invasive treatment modalities including physical therapy, intra-articular steroids and/or oral NSAIDS; viii. Subject has not had recent invasive surgical procedures of the knee within the following intervals in relation to the time of signing Informed Consent:- 2 weeks for steroid injection - 4 weeks for radiofrequency, cryoablation or hyaluronic acid (HA) injection ix. Subject noted good (\> 75%) but only temporary relief for at least 2 hours from an infrapatellar saphenous nerve injection with local anesthetic; x. Subject is deemed to be neuro-psycho-socially appropriate for implantation therapies based of assessment of a Clinical Psychologist.

Exclusion Criteria:

xi. Significant contralateral knee pain that would influence their level of activity greater to 6 on the modified-Mankosky Pain Scale; xii. Hip or foot pain greater than knee pain; xiii. Neurogenic or vascular claudication; xiv. Subject has been diagnosed with Kellgren-Lawrence Grade IV knee osteoarthritis, confirmed by X-ray studies conducted in the last year; xv. Uncontrolled major depression or uncontrolled psychiatric disorders; xvi. Uncontrolled or acute medical illnesses including coagulopathy, renal insufficiency, chronic liver dysfunction, progressive neurological deficit, infection, unstable angina, and severe chronic obstructive pulmonary disease; xvii. Chronic severe conditions that could interfere with the interpretations of the outcome assessments for pain and bodily function (eg. Rheumatoid arthritis, severe spinal stenosis, activity-limiting cardiac disease); xviii. Women who are pregnant or planning to become pregnant, lactating; xix. Body mass index (BMI) greater than 40 (morbid obesity); xx. Subjects with multiple complaints involving concomitant knee, foot, or ankle pathology or radiculopathy, that will not be amenable to study due to the overlap of pain complaints; xxi. Subject has been examined and has been deemed to be inappropriate for the procedure based on anatomical restrictions; xxii. Lymphedema or stasis ulcers or other conditions that would compromise the surgical site; xxiii. History of adverse reaction to local anesthetic drugs; xxiv. Worker's compensation claimants; xxv. Incarcerated or has an ankle position locator; xxvi. Documented allergy to device material components; xxvii. Known or suspected substance abuse within the last 2 years; xxviii. Pacemaker or implanted defibrillator; xxix. Participation in another clinical study that could confound the results of this study; xxx. Based on the opinion of the investigator any legal or medical concerns that would preclude his/her enrollment in the study or potentially confound the results; xxxi. Any other implanted active medical devices in the same site.

Primary outcomes:
measure: Responder rate
timeFrame: 1 month
Secondary outcomes:
measure: Mankoski pain scale
timeFrame: 1 month
measure: Koos Jr
timeFrame: 1 month
measure: Global Perceived Effect scales (GPES)
timeFrame: 1 month
measure: McGill Short Form (SF-MPQ-2)
timeFrame: 1 month
measure: Neuropathic pain questionnaire (DN4)
timeFrame: baseline
measure: Work status (if working);
timeFrame: 1 month
measure: Percentage Increase in Ability to do Knee Bends and Walking Tolerance
timeFrame: 1 month
measure: Range of Motion
timeFrame: 1 month
measure: Timed Up & Go (TUG)
timeFrame: 1 month
measure: Medication: Change in concomitant pain medication usage
timeFrame: 1 month
Other outcomes:
measure: Treadmill
timeFrame: 1 month
Locations:
city: Placentia
country: United States
facility: Western Clinical Research
state: California
city: Denver
country: United States
facility: Colorado Pain Care, LLC
state: Colorado
city: Fort Lauderdale
country: United States
facility: Holy Cross Hospital, Inc
state: Florida
city: Trinity
country: United States
facility: Florida Joint Care Institute
state: Florida
city: Jasper
country: United States
facility: Southern Pain and research
state: Georgia
city: Newnan
country: United States
facility: Vista Clinical Research/Summit Spine & Joint Centers
state: Georgia
city: Las Vegas
country: United States
facility: Desert Orthopaedic Center
state: Nevada
city: Dayton
country: United States
facility: Orthopedic Associates of Southwest Ohio
state: Ohio
city: Loveland
country: United States
facility: Premier Pain Treatment
state: Ohio
city: Miamisburg
country: United States
facility: Kettering Health
state: Ohio
city: Austin
country: United States
facility: Austin Orthopedic Institute
state: Texas
city: Houston
country: United States
facility: Performance pain and sports medicine
state: Texas
city: San Antonio
country: United States
facility: Advanced Spine and Pain Center
state: Texas
Study officials:
References: