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NCT Number: NCT07696988

PNS to Improve Vascular Function and Limb Health in Veterans

Establishing a sensitive, scalable physiological test for neurovascular reflex integrity and investigating whether targeted peripheral neural stimulation can enhance perfusion and vasodilatory responsiveness.

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Key information

Conditions

Lower Limb Amputees Diabetes Diabetes Mellitus Endocrine System Diseases Glucose Metabolism Disorders Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Louis Stokes VA Medical Center, Cleveland, OH

Cleveland, Ohio, 44106-1702, United States

About this study

The overarching goal of this project is to define how targeted afferent activation can be used to restore impaired neurovascular reflexes, improve skin perfusion, and ultimately prevent further decline in limb health in Veterans. By integrating functional and structural imaging with neural modulation, this work will establish foundational evidence for diagnostic and therapeutic strategies aimed at early detection of neurovascular decline and prevention of tissue breakdown in both Diabetic Peripheral Neuropathy (DPN) and residual-limb contexts. Furthermore, this work will establish the feasibility of preventing or delaying the mechanical trauma of the insensate distal limb which invariably leads to deep pressure injuries, infections, and amputation in Veterans with DPN. The findings have the potential to transform care by enabling earlier diagnosis, improving neurovascular responsiveness, and optimizing neuromodulation protocols to prevent skin complications, delay progression toward amputation, and improve quality of life in Veterans with DPN or limb loss.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Inclusion criteria

- All Participants:

  • English-speaking
  • Veteran

Inclusion criteria

- Diabetic Peripheral Neuropathy (DPN) Participants:

  • Confirmed diagnosis of type 1 or type 2 diabetes mellitus for at least 5 years
  • Clinical signs and/or symptoms consistent with diabetic peripheral neuropathy Or confirmation of neuropathy via physical exam

Inclusion criteria

- Lower Limb Amputees:

  • Unilateral transtibial or transfemoral amputation
  • Medically stable for at least 3 months
  • For the designated subset of the limb-loss cohort (n = 6): implanted with C-FINEs on the sciatic and/or tibial nerves

Exclusion criteria

Exclusion criteria

- All Participants:

  • Severe neurological disorders impairing ambulation
  • Visual or hearing impairments interfering with study participation
  • Cardiovascular or respiratory conditions posing risk during participation
  • Cognitive or psychiatric conditions compromising informed consent
  • Participation in other clinical trials interfering with outcomes
  • Pregnancy
  • History of photosensitivity or known sensitivity to laser light

Additional Exclusion Criteria - Amputees:

  • Active skin breakdown or infection at residual limb
  • Significant phantom or residual limb pain interfering with study procedures
  • Bilateral lower-limb amputation

Treatment and study plan

Chronically Implanted Neural and Muscular Interface

Device

The implanted neural and and muscular interface will be used to characterize neurovascular reflex testing (thermal axon reflex & pressure-induced vasodilation) and microvascular imaging using Laser Doppler Flowmetry and PAI. Reflex responses will be evaluated under baseline and stimulation conditions (sham, tonic, biomimetic), with direct stimulation performed by the CFINE cohort for modality comparison. Structural-functional relationships will be modeled by integrating metrics from PAI with reflex outcomes.

Peripheral Nerve Stimulation (PNS)

Device

The cutaneous peripheral nerve stimulation interface will be used to characterize neurovascular reflex testing (thermal axon reflex & pressure-induced vasodilation) and microvascular imaging using Laser Doppler Flowmetry and PAI. Reflex responses will be evaluated under baseline and stimulation conditions (sham, tonic, biomimetic). Structural-functional relationships will be modeled by integrating metrics from PAI with reflex outcomes.

Primary outcomes

  1. Cutaneous Vascular Conductance

    Time frame: baseline and visits 1-15 until study completion, average 1 year

    Autonomic reflex testing including thermal axon reflex and pressure induced vasoconstriction will be applied. The cutaneous blood flow in the lower limb will be measured using laser doppler flowmetry. The flux is divided by mean arterial pressure to calculate cutaneous vascular conductance. This provides a physiologically relevant metric of microvascular control by accounting for systemic pressure fluctuations

  2. Vessel Density

    Time frame: baseline and visits 1-15 until study completion, average 1 year

    Defined as the percentage of tissue volume occupied by vascular structures. The investigators use photoacoustic imaging of microvascular structure to quantify microvascular structural integrity at distal and proximal skin sites. From the reconstructed volumetric data, the investigators will extract the vessel density

  3. Tissue Oxygen Saturation

    Time frame: baseline and visits 1-15 until study completion, average 1 year

    Tissue oxygen saturation or sO2 will be measured during different conditions of the study such as thermal axon reflex and pressure induced vasoconstriction using reflectance spectroscopy

  4. Mean Vessel Diameter

    Time frame: baseline and visits 1-15 until study completion, average 1 year

    Calculated from the cross-sectional profiles of resolved vessels obtained from the photoacoustic imaging of microvascular structures

  5. Hemoglobin Oxygenation

    Time frame: baseline and visits 1-15 until study completion, average 1 year

    From photoacoustic imaging, hemoglobin oxygenation is derived and compared across different study conditions

Interested in participating?

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Sponsors and collaborators

Lead sponsor

VA Office of Research and Development

Fed

Collaborators

  • Case Western Reserve University

Registry information

Official study title

Peripheral Neural Stimulation to Improve Microvascular Function and Limb Health in Veterans With Diabetic Peripheral Neuropathy

Important dates

Study start
2026
Primary completion
2030
Study completion
2030
First posted
Jul 10, 2026
Registry last updated
Aug 21, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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