NCT07696988

Brief Summary

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

Trial Health

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Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
42

participants targeted

Target at P25-P50 for not_applicable

Timeline
44mo left

Started Nov 2026

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 23, 2026

Completed
17 days until next milestone

First Posted

Study publicly available on registry

July 10, 2026

Completed
4 months until next milestone

Study Start

First participant enrolled

November 2, 2026

Expected
3.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 30, 2030

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 30, 2030

Last Updated

July 10, 2026

Status Verified

July 1, 2026

Enrollment Period

3.6 years

First QC Date

June 23, 2026

Last Update Submit

July 8, 2026

Conditions

Lower Limb AmputeesDiabetes

Keywords

lower extremity limb lossDiabetes

Outcome Measures

Primary Outcomes (5)

  • 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

Study Arms (2)

Implanted Neural and Muscular Interface

EXPERIMENTAL

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 InterfaceDevice: Peripheral Nerve Stimulation (PNS)

Peripheral nerve stimulation

EXPERIMENTAL

30 able body participants and 12 participants with unilateral lower-limb loss with receive peripheral nerve stimulation

Device: Peripheral Nerve Stimulation (PNS)

Interventions

Chronically Implanted Neural and Muscular InterfaceDEVICE

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.

Implanted Neural and Muscular Interface
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.

Implanted Neural and Muscular InterfacePeripheral nerve stimulation

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • English-speaking
  • 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
  • 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

You may not qualify if:

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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Louis Stokes VA Medical Center, Cleveland, OH

Cleveland, Ohio, 44106-1702, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus

Condition Hierarchy (Ancestors)

Glucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System Diseases

Study Officials

  • Hamid Charkhkar, PhD

    Louis Stokes VA Medical Center, Cleveland, OH

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Hamid Charkhkar, PhD

CONTACT

(216) 791-3800Hamid.Charkhkar@va.gov

Jessica R Jarvela, MS BS

CONTACT

(216) 791-3800Jessica.Jarvela@va.gov

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NON RANDOMIZED
Masking
SINGLE
Who Masked
PARTICIPANT
Purpose
HEALTH SERVICES RESEARCH
Intervention Model
PARALLEL
Sponsor Type
FED
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 23, 2026

First Posted

July 10, 2026

Study Start (Estimated)

November 2, 2026

Primary Completion (Estimated)

May 30, 2030

Study Completion (Estimated)

May 30, 2030

Last Updated

July 10, 2026

Record last verified: 2026-07

Data Sharing

IPD Sharing
Will not share

Locations

US(1)