Clinical trial NCT06480786: SCS for Patient With Painful Diabetic Neuropathy and Peripheral Arterial Disease
Official title: Spinal Cord Stimulation for Patients With Painful Diabetic Neuropathy and Peripheral Arterial Disease: Mechanistic Insights From a Single-center, Randomized, Blinded, Sham-controlled Cross-over Proof-of-concept Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Peripheral Arterial Disease
Painful Diabetic Neuropathy
Diabetes Mellitus, Type 2
Chronic Pain
Spinal Cord Stimulation
Chronic Pain Syndrome
Limb Pain
Lead sponsor: University of Nebraska
Sponsor class: OTHER
Collaborators: name: Nevro Corp
First posted: 2024-06-28
Enrollment: 15
Sex: ALL
Minimum age (years): 19
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 1:1 cross over design
Primary purpose: TREATMENT

Brief summary: Peripheral arterial disease (PAD) affects over 230 million adults worldwide and is a highly morbid, costly, and disabling condition. Ischemic leg pain drives disability in PAD patients and results from oxygen supply-demand mismatch, autonomic dysfunction, and muscle breakdown. This leg pain, which is unresponsive to traditional pharmacotherapy, limits the patient's tolerance to exercise, which is an important disease-modifying intervention. Spinal cord stimulation is a well-established therapy for medically intractable pain, including painful diabetic neuropathy (PDN) and ischemic pain, but is not part of the standard-of-care for PAD despite limited promising clinical data. Early studies used first-generation, tonic stimulation devices, but with these it was impossible to perform sham-controlled trials to test the treatment. Since then, new types of waveform treatments, including high-frequency spinal cord stimulation (SCS), have been shown to be more effective in the treatment of intractable pain. While high-frequency SCS is approved for PDN treatment, it has never been tested in the treatment of claudication pain from PAD.

This study will enroll up to 15 participants between the ages of 19 and 89 who have PAD and PDN and are successfully implanted with a permanent SCS. Twelve weeks after SCS implantation, participants will receive two weeks of stimulation and two weeks of sham intervention, in random starting order. Blood flow, blood pressure, skin oxygen levels, and participant reported pain int the lower extremities will be assessed before SCS implantation, 12 weeks after SCS implantation and during each of the treatment periods. Participants will also complete a quality of life survey at the same time points. Comparisons of these measurements with the baseline and post-implantation measurements to determine the effects of SCS.

Detailed description: Peripheral arterial disease (PAD) affects over 230 million adults worldwide and is a highly morbid, costly, and disabling condition. Ischemic leg pain drives disability in PAD patients and results from oxygen supply-demand mismatch, autonomic dysfunction, and muscle breakdown. This leg pain, which is unresponsive to traditional pharmacotherapy, limits the patient's tolerance to exercise, which is an important disease-modifying intervention. Spinal cord stimulation is a well-established therapy for medically intractable pain, including painful diabetic neuropathy (PDN) and ischemic pain, but is not part of the standard-of-care for PAD despite limited promising clinical data. Early studies used first-generation, tonic stimulation devices, but with these it was impossible to perform sham-controlled trials to test the treatment. Since then, new types of waveform treatments, including high-frequency spinal cord stimulation (SCS), have been shown to be more effective in the treatment of intractable pain. While high-frequency SCS is approved for PDN treatment, it has never been tested in the treatment of claudication pain from PAD.

This study will enroll up to 15 participants between the ages of 19 and 89 who have PAD (ankle-brachial index under 0.90 or vascular imaging, and experience pain from walking with a pain level of at least 6 cm for at least 3 months )and PDN and who meet inclusion criteria for permanent spinal cord stimulator (SCS) placement. Participants must also have diabetes with symptoms of neuropathy, have a starting pain level of at least 5 cm on a visual pain scale and Vascular Quality of Life Questionnaire score of 5.5 or less.

The study begins with an initial evaluation visit, then a follow-up visit 12 weeks after permanent SCS implantation and optimization. Participants will then be randomized to start in the SCS group or the sham intervention group. Each of these interventions will be conducted for two weeks, then participants will switch to the other intervention in a cross over design. Blood flow, blood pressure, skin oxygen levels, and participant reported pain int the lower extremities will be assessed before SCS implantation, 12 weeks after SCS implantation and during each of the treatment periods. Participants will also complete a quality of life survey at the same time points. Comparisons of these measurements with the baseline and post-implantation measurements to determine the effects of SCS. The study intervention lasts for 4 weeks, after which participants will return to standard SCS care.

Eligibility criteria: Inclusion Criteria:

* 19 years to 89 years old
* Diagnosed diabetes mellitus
* Signs or symptoms of neuropathy and maximum baseline visual-analog pain scale ≥ 5 cm and peripheral arterial disease (diagnosed by ankle-brachial index \< 0.90 or vascular imaging studies) with claudication and exertion-induced visual-analog pain scale ≥ 6 cm for a minimum of 3 months
* Successful spinal cord stimulator (SCS) trial (\>50% relief of chronic lower extremity pain) and will have a new permanent SCS placed prior to study intervention

Exclusion Criteria:

* Uncontrolled psychological or psychiatric disorder
* Inability to hold antithrombotic therapy per the American Society of Regional Anesthesia guidelines
* Non-healing wounds
* Gangrene
* Critical limb ischemia
* Prior lower extremity amputation
* Inability to adhere to study follow-up
* Mechanical spine instability based on flexion/extension radiographs of the lumbar spine
* Prior or current spinal cord stimulator implant

Primary outcomes:
measure: High-frequency Spinal Cord Stimulation Effect on Analgesia
timeFrame: Baseline, 12 week follow-up after permanent spinal cord simulator, week 14 intervention #1 , week 16 intervention #2
Secondary outcomes:
measure: High-frequency Spinal Cord Stimulation Effect on Quality of Life
timeFrame: Baseline, 12 week follow up after permanent spinal cord simulator, week 14 intervention #1 , week 16 intervention #2
measure: High-frequency Spinal Cord Stimulation Effect on Blood Flow
timeFrame: Baseline, 12 week follow up after permanent spinal cord simulator, week 14 intervention #1 , week 16 intervention #2
measure: High-frequency Spinal Cord Stimulation Effect on Autonomic Control
timeFrame: Baseline, 12 week follow-up after permanent spinal cord simulator, week 14 intervention #1 , week 16 intervention #2
Other outcomes:
Locations:
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
Study officials:
affiliation: University of Nebraska
name: Peter Pellegrino, MD
role: PRINCIPAL_INVESTIGATOR
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