SCS for Patient With Painful Diabetic Neuropathy and Peripheral Arterial Disease

October 21, 2025 updated by: University of Nebraska

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

15

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • Recruiting
        • University of Nebraska Medical Center
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Active Spinal Cord Stimulation
Therapeutic spinal cord stimulation titrated at 12 weeks post operative at standard clinical practice.
Device: Spinal cord stimulation
active spinal cord stimulation
Sham Comparator: Sham Stimulation
Sub-threshold low frequency spinal cord stimulation to provide no analgesic benefit but serve as a sham control.
Device: Sham stimulation
Sham stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
High-frequency Spinal Cord Stimulation Effect on Analgesia
Time Frame: Baseline, 12 week follow-up after permanent spinal cord simulator, week 14 intervention #1 , week 16 intervention #2
The visual analogue scale (VAS) will be used by participants to report lower extremity pain during interventions. The VAS score is a10-cm line that represents a continuum between "no pain" and "worst pain."
Baseline, 12 week follow-up after permanent spinal cord simulator, week 14 intervention #1 , week 16 intervention #2

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
High-frequency Spinal Cord Stimulation Effect on Quality of Life
Time Frame: Baseline, 12 week follow up after permanent spinal cord simulator, week 14 intervention #1 , week 16 intervention #2
Quality of life changes from high-frequency high-frequency spinal cord stimulation (SCS) will be measured by the Vascular Quality of Life Questionnaire (VASCUQOL). This instrument has 25 questions covering pain, symptoms, activities, social, and emotional. Each question has seven responses from 1 (worst) to 7 (best).
Baseline, 12 week follow up after permanent spinal cord simulator, week 14 intervention #1 , week 16 intervention #2
High-frequency Spinal Cord Stimulation Effect on Blood Flow
Time Frame: Baseline, 12 week follow up after permanent spinal cord simulator, week 14 intervention #1 , week 16 intervention #2
Changes in blood flow from high-frequency spinal cord stimulation (SCS) will measure lower extremity capillary digit blood flow flow by laser speckle imaging.
Baseline, 12 week follow up after permanent spinal cord simulator, week 14 intervention #1 , week 16 intervention #2
High-frequency Spinal Cord Stimulation Effect on Autonomic Control
Time Frame: Baseline, 12 week follow-up after permanent spinal cord simulator, week 14 intervention #1 , week 16 intervention #2
Changes in autonomic control from high-frequency spinal cord stimulation (SCS) will measure sympathetic vasomotion by volume-clamp method on digits of the hand and laser speckle imaging on the lower extremities.
Baseline, 12 week follow-up after permanent spinal cord simulator, week 14 intervention #1 , week 16 intervention #2

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Nebraska

Collaborators

Nevro Corp

Investigators

  • Principal Investigator: Peter Pellegrino, MD, University of Nebraska

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 18, 2024

Primary Completion (Estimated)

January 1, 2027

Study Completion (Estimated)

July 1, 2027

Study Registration Dates

First Submitted

June 24, 2024

First Submitted That Met QC Criteria

June 24, 2024

First Posted (Actual)

June 28, 2024

Study Record Updates

Last Update Posted (Estimated)

October 22, 2025

Last Update Submitted That Met QC Criteria

October 21, 2025

Last Verified

October 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0623-24-FB

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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