PNS to Improve Vascular Function and Limb Health in Veterans

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

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

Study Overview

• Status: Not yet recruiting
• Conditions: Diabetes; Lower Limb Amputees
• Intervention / Treatment: Device: Chronically Implanted Neural and Muscular Interface; Device: Peripheral Nerve Stimulation (PNS)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 42
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jessica R Jarvela, MS BS; Phone Number: 63801 (216) 791-3800; Email: Jessica.Jarvela@va.gov
• Study Contact Backup: Name: Hamid Charkhkar, PhD; Phone Number: 62924 (216) 791-3800; Email: Hamid.Charkhkar@va.gov

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44106-1702
      • Louis Stokes VA Medical Center, Cleveland, OH
      • Contact: Aarika Sheehan, DPT; Phone Number: 65832 (216) 791-3800; Email: Aarika.Sheehan@va.gov
      • Contact: Jessica R Jarvela, MS BS; Phone Number: 63801 216-791-3800; Email: Jessica.Jarvela@va.gov
      • Principal Investigator: Hamid Charkhkar, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Inclusion Criteria - All Participants:

• English-speaking

Inclusion Criteria - 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Implanted Neural and Muscular Interface; 6 lower limb loss participants who have already been chronically implanted with neural and muscular interfaces to allow for direct stimulation	Device: Chronically Implanted Neural and Muscular Interface; 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.; Device: Peripheral Nerve Stimulation (PNS); 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.
Experimental: Peripheral nerve stimulation; 30 able body participants and 12 participants with unilateral lower-limb loss with receive peripheral nerve stimulation	Device: Peripheral Nerve Stimulation (PNS); 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cutaneous Vascular Conductance	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	baseline and visits 1-15 until study completion, average 1 year
Vessel Density	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	baseline and visits 1-15 until study completion, average 1 year
Tissue Oxygen Saturation	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	baseline and visits 1-15 until study completion, average 1 year
Mean Vessel Diameter	Calculated from the cross-sectional profiles of resolved vessels obtained from the photoacoustic imaging of microvascular structures	baseline and visits 1-15 until study completion, average 1 year
Hemoglobin Oxygenation	From photoacoustic imaging, hemoglobin oxygenation is derived and compared across different study conditions	baseline and visits 1-15 until study completion, average 1 year

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Collaborators: Case Western Reserve University
• Investigators: Principal Investigator: Hamid Charkhkar, PhD, Louis Stokes VA Medical Center, Cleveland, OH

Study record dates

Study Major Dates

• Study Start (Estimated): November 2, 2026
• Primary Completion (Estimated): May 30, 2030
• Study Completion (Estimated): May 30, 2030

Study Registration Dates

• First Submitted: June 23, 2026
• First Submitted That Met QC Criteria: July 8, 2026
• First Posted (Actual): July 10, 2026

Study Record Updates

• Last Update Posted (Actual): July 10, 2026
• Last Update Submitted That Met QC Criteria: July 8, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Diabetes; lower extremity limb loss
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Nutritional and Metabolic Diseases; Diabetes Mellitus
• Other Study ID Numbers: RRD5-006-25W; RD001968-01 (Other Grant/Funding Number: VA Merit); 1584038 (Other Identifier: IRB)

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