Clinical trial NCT05200858: Transcutaneous Electrical Nerve Stimulation (TENS) in Patients With Postacute Sequelae of Sars-CoV-2
Official title: Transcutaneous Electrical Nerve Stimulation For Lower Extremity In Patients With Neurogenic Pain - A Proof Of Concept Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Postacute Sequelae of Sars-CoV-2
Post-Acute COVID-19 Syndrome
Widespread Chronic Pain
Fatigue Syndrome, Chronic
Gait, Unsteady
Keywords: Transcutaneous nerve electrical stimulation
Pain
Fatigue
Lead sponsor: Baylor College of Medicine
Sponsor class: OTHER
Collaborators: name: NeuroMetrix, Inc.
First posted: 2022-01-21
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Participants, who satisfy the inclusion and exclusion criteria and sign the informed consent form will be randomly assigned with ratio of 1:1 into two groups. One group will utilize TENS high-dose devices (Intervention group, IG); the other group will utilize TENS low-dose devices (Placebo group, PG).

Both groups will receive their respective devices at the initial visit (BL) and will be asked to return in 4 weeks for follow-up assessment (4W visit). At this 4 week visit, study participants will be unblinded and the IG will keep their high-dose device, while the PG will switch from low-dose to high-dose TENS device. Study participants will return for a final in-person visit at the 8th week (8W), which will include the assessments described above. Throughout this 8-week period the participants may receive follow-up phone calls assessing their compliance. All subjects will keep the commercial (high-dose TENS) device after completion of the 8-week study.
Primary purpose: SUPPORTIVE_CARE

Brief summary: The purpose of the pilot study is to examine acceptability and proof of concept effectiveness of a wireless TENS technology to address PASC associated FM. Sample size (n=30) is convenient and designed to explore acceptability and feasibility. Participants, who satisfy the inclusion and exclusion criteria and sign the informed consent form will be randomly assigned with ratio of 1:1 into two groups. One group will utilize TENS high-dose devices (Intervention group, IG); the other group will utilize TENS low-dose devices (Placebo group, PG). The baseline measurements will be performed, and the patients will take the programmed device home for a duration of 4 weeks. Then, the patients will come back after four weeks (4W). At this 4th week visit, both groups will be unblinded and the IG will keep their high-dose TENS device and the PG group will switch from a low-dose TENS to a high-dose TENS device. Both groups will continue to deliver 3-5 hour of stimulation daily, until their final 8th week follow up visit (8W). The primary outcome will be pain. Secondary outcomes include fatigue, limb strength and perfusion, gait assessment (cadence, stride time, double support), balance, pulse oximetry, and quality of life. The coordinator will utilize a weekly spreadsheet showing utilization (therapy sessions/day, logged in the Quell health Cloud) so compliance can be monitored and those that are not using the device can be encouraged.

Detailed description: Postacute Sequelae of Sars-CoV-2 (PASC) is an emerging entity that has been clearly recognized by musculoskeletal pain, fatigue, cognitive, and sleep disturbances, among other symptoms, in patients who have recovered from severe Sars-CoV-2 infection. Hospitalized survivors have reported a significant excess burden of many of these symptoms up to 8 months after discharge. Particularly in the lower extremity, musculoskeletal illness has been associated with prolonged immobilization, high-risk comorbidities, and the use of glucocorticoids that is commonly administered to these patients. These manifestations are the cardinal symptoms of fibromyalgia (FM), a condition thought to be caused by hyperactive sensory signaling due to central sensitization as well as deficient endogenous pain inhibition, triggered among others, by viral infections. Consequently, FM sequelae are one of the most common long-term complications seen in PASC. Thus, it is expected to impose a serious burden on different medical specialties in a near future. In a population that has persistent lack of symptom resolution such as FM, adherence to therapy could be challenging. Patients with constant pain, fatigue, and sleep disturbances, are difficult to keep motivated, especially those pain-medication dependents that often present low quality of life. One practical solution to address the symptomatology characteristic of FM is the use of transcutaneous electrical stimulation therapy (TENS). Studies have demonstrated its ability to manage pain and fatigue in patients with peripheral neuropathy and FM, and has shown to effectively improve lower-extremity perfusion and oxygen delivery in patients with ischemic lesions. However, TENS has not yet been explored for PASC. Since this technology is dose-dependent, the investigators propose a practical daily-basis therapy that patients with persistent associated FM due to previous COVID-19 infection could apply at home, thus, addressing PASC without relying only on medication. In this matter, Neurometrix Inc. (Woburn, MA, USA) has created a wireless TENS device (Quell®) to address pain, gait, sleep, and fatigue. This technology is placed in the lower-extremity and works through the stimulation of nerves that carry non-painful sensations (A-beta fibers) by closing a neurological "gate" in the spinal cord, thus, reducing transmission from pain nerves (A-delta and C fibers) to the brain. This device utilizes a wireless technology manageable through a smart phone application (Quell App) that also tracks symptom-status. Moreover, Baylor College of Medicine has created the Post-COVID-19 Clinic (McNair Campus, BCM St Luke's, Houston, TX, USA) supervised by specialists in critical and pulmonary care. This Clinic has a high volume of patients that present with PASC, particularly those with associated FM (i.e., persistent muscle pain, fatigue, weakness, atrophy, sleep problems, and/or anxiety). Therefore, the investigators believe Baylor institution is a suitable place to perform this pilot study.

Eligibility criteria: Inclusion Criteria:

* Previous COVID-19 infection
* Persistent symptoms of pain, fatigue, weakness, or poor gait and balance that were not present before COVID-19 infection
* Willing to attend clinic for assessments

Exclusion Criteria:

* Severe cognitive decline reduces their ability to interact with the TENS mobile app
* Major visual or hearing weakness reduces the ability to interact with TENS mobile app
* Unable to walk independently for a distance of 10 meter
* Major foot problems such as active lower extremity wounds, major foot deformity (e.g., Charcot Foot), previous major amputations, and claudication
* Demand-type cardiac pacemaker, implanted defibrillator, or other implanted electronic devices; and any conditions that may interfere with outcomes or increase the risk of the use TENS based on the judgement of clinicians

Primary outcomes:
measure: Mean Change in Functional Interference From Pain From Baseline to 4 Weeks (Blinded Phase)
timeFrame: baseline to 4 weeks
Secondary outcomes:
measure: Mean Change in Pain Severity From Baseline to 4 Weeks (Blinded Phase)
timeFrame: Baseline to 4 weeks
measure: Mean Change in Functional Interference From Fatigue From Baseline to 4 Weeks (Blinded Phase)
timeFrame: Baseline to 4 weeks
measure: Stride Time at 4 Weeks During a Simple Walking Task (Blinded Phase)
timeFrame: at 4 weeks
measure: Cadence at 4 Weeks During a Simple Walking Task (Blinded Phase)
timeFrame: at 4 weeks
measure: Double Support Phase at 4 Weeks During a Simple Walking Task (Blinded Phase)
timeFrame: at 4 weeks
measure: Cadence at 4 Weeks During a Dual Walking Task (Blinded Phase)
timeFrame: at 4 weeks
measure: Cadence at 4 Weeks During a Fast Walking Task (Blinded Phase)
timeFrame: at 4 weeks
Other outcomes:
measure: Stride Time at 4 Weeks During a Dual Walking Task (Blinded Phase)
timeFrame: at 4 weeks
measure: Stride Time at 4 Weeks During a Fast Walking Task (Blinded Phase)
timeFrame: at 4 weeks
measure: Gastrocnemius Muscle Endurance (Muscle Sustained Contraction) in Response to Electrical Stimulation at 4 Weeks (Blinded Phase)
timeFrame: at 4 weeks
measure: Frailty at 4 Weeks (Blinded Phase)
timeFrame: up to 4 weeks
measure: Sural Nerve Conduction Velocity at 4 Weeks (Blinded Phase)
timeFrame: 4 weeks
measure: Ankle Strength at 4 Weeks (Blinded Phase)
timeFrame: up to 4 weeks
measure: Plantar Tissue Oxygen Saturation at 4 Weeks (Blinded Phase)
timeFrame: up to 4 weeks
measure: Mean Daily Step Count at 4 Weeks (Blinded Phase)
timeFrame: up to 4 weeks
measure: Sleep Duration at 4 Weeks (Blinded Phase)
timeFrame: up to 4 weeks
measure: Sural Nerve Amplitude at 4 Weeks (Blinded Phase)
timeFrame: at 4 weeks
measure: Mean Change in Functional Interference From Pain at 8 Weeks (Unblinded Phase)
timeFrame: from week 4 to week 8
measure: Mean Change in Pain Severity From 4 Weeks to 8 Weeks (Unblinded Phase)
timeFrame: 4 weeks to 8 weeks
measure: Mean Change in Functional Interference From Fatigue From 4 Weeks to 8 Weeks (Unblinded Phase)
timeFrame: 4 weeks to 8 weeks
measure: Stride Time at 8 Weeks During a Simple Walking Task (Unblinded Phase)
timeFrame: at 8 weeks
measure: Gastrocnemius Muscle Endurance (Muscle Sustained Contraction) in Response to Electrical Stimulation at 8 Weeks (Unblinded Phase)
timeFrame: at 8 weeks
measure: Frailty at 8 Weeks (Unblinded Phase)
timeFrame: at 8 weeks
measure: Sural Nerve Conduction Velocity at 8 Weeks (Unblinded Phase)
timeFrame: at 8 weeks
measure: Ankle Strength at 8 Weeks (Unblinded Phase)
timeFrame: at 8 weeks
measure: Plantar Tissue Oxygen Saturation at 8 Weeks (Unblinded Phase)
timeFrame: at 8 weeks
measure: Mean Daily Step Count at 8 Weeks (Unblinded Phase)
timeFrame: Starting at 4 weeks up to 8 weeks
measure: Sleep Duration at 8 Weeks (Unblinded Phase)
timeFrame: Starting at 4 weeks up to 8 weeks
measure: Sural Nerve Amplitude at 8 Weeks (Unblinded Phase)
timeFrame: up to 8 weeks
measure: Double Support Phase at 4 Weeks During a Dual Walking Task (Blinded Phase)
timeFrame: at 4 weeks
measure: Double Support Phase at 4 Weeks During a Fast Walking Task (Blinded Phase)
timeFrame: at 4 weeks
measure: Double Support Phase at 8 Weeks During a Simple Walking Task (Unblinded Phase)
timeFrame: at 8 weeks
measure: Double Support Phase at 8 Weeks During a Dual Task (Unblinded Phase)
timeFrame: at 8 weeks
measure: Stride Time at 8 Weeks During a Dual Task (Unblinded Phase)
timeFrame: at 8 weeks
measure: Stride Time at 8 Weeks During a Fast Walk Task (Unblinded Phase)
timeFrame: at 8 weeks
measure: Cadence at 8 Weeks During a Simple Walking Task (Unblinded Phase)
timeFrame: at 8 weeks
measure: Cadence at 8 Weeks During a Dual Task (Unblinded Phase)
timeFrame: at 8 weeks
measure: Cadence at 8 Weeks During a Fast Walking Task (Unblinded Phase)
timeFrame: at 8 weeks
Locations:
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
Study officials:
References: