Lower Limb AmputeesNCT07696988
PNS to Improve Vascular Function and Limb Health in Veterans
A study testing Chronically Implanted Neural and Muscular Interface and Peripheral Nerve Stimulation (PNS) in people with Lower Limb Amputees and Diabetes, run by VA Office of Research and Development at 1 site in United States.
Trial summary
Establishing a sensitive, scalable physiological test for neurovascular reflex integrity and investigating whether targeted peripheral neural stimulation can enhance perfusion and vasodilatory responsiveness. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Lower Limb Amputees, Diabetes
- What is being tested?
- Chronically Implanted Neural and Muscular Interface and Peripheral Nerve Stimulation (PNS)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Nov 2026to 30 May 2030
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
- 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
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
Louis Stokes VA Medical Center, Cleveland, OH
Cleveland, Ohio, 44106-1702
Jessica R Jarvela, MS BS, (216) 791-3800 ext. 63801, Jessica.Jarvela@va.gov
Aarika Sheehan, DPT, (216) 791-3800 ext. 65832, Aarika.Sheehan@va.gov
About this study
Official title: 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.
Read the 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.
- Conditions
- Lower Limb Amputees, Diabetes
- Being tested
- Chronically Implanted Neural and Muscular Interface, Peripheral Nerve Stimulation (PNS)
- Keywords
- lower extremity limb loss, Diabetes
- Medical subject headings
- Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Device: Chronically Implanted Neural and Muscular Interface; Device: 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 Receives: Device: Peripheral Nerve Stimulation (PNS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: baseline and visits 1-15 until study completion, average 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2026
- Study start2 Nov 2026 (estimated)
- Primary completion30 May 2030 (estimated)
- Study completion30 May 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lower Limb AmputeesStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Health services research
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 42 participants (estimated)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Collaborators
- Case Western Reserve University
- Responsible party
- Sponsor
- Investigators
- Hamid Charkhkar, PhD, Principal investigator, Louis Stokes VA Medical Center, Cleveland, OH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07696988
- Sponsor's protocol ID
- RRD5-006-25W
- Other IDs
- RD001968-01, 1584038
- Status last verified
- Aug 2026
- First submitted
- 23 Jun 2026
- Last updated
- 21 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Peripheral Neural Stimulation to Improve Microvascular Function and Limb Health in Veterans With Diabetic Peripheral Neuropathy
- ClinicalTrials.gov ID
- NCT07696988
- Acronym / sponsor ID
- RRD5-006-25W
- Conditions
- Lower Limb Amputees, Diabetes
- Keywords
- lower extremity limb loss, Diabetes
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 42 participants (estimated)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Collaborators
- Case Western Reserve University
- Study start
- 2 Nov 2026 (estimated)
- Primary completion
- 30 May 2030 (estimated)
- Study completion
- 30 May 2030 (estimated)
- First posted
- 10 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Establishing a sensitive, scalable physiological test for neurovascular reflex integrity and investigating whether targeted peripheral neural stimulation can enhance perfusion and vasodilatory responsiveness.
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 design
- Primary purpose
- Health services research
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Implanted Neural and Muscular Interface | Experimental | Device: Chronically Implanted Neural and Muscular Interface, Device: Peripheral Nerve Stimulation (PNS)6 lower limb loss participants who have already been chronically implanted with neural and muscular interfaces to allow for direct stimulation |
| Peripheral nerve stimulation | Experimental | Device: Peripheral Nerve Stimulation (PNS)30 able body participants and 12 participants with unilateral lower-limb loss with receive peripheral nerve stimulation |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- English-speaking
- Veteran
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Chronically Implanted Neural and Muscular InterfaceThe 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 | Implanted Neural and Muscular Interface |
| 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. | Device | Implanted Neural and Muscular Interface, Peripheral nerve stimulation |
Primary outcome
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
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
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
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
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Hamid Charkhkar, PhD principal investigator
Louis Stokes VA Medical Center, Cleveland, OH
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Chronically Implanted Neural and Muscular Interface and Peripheral Nerve Stimulation (PNS) in people with Lower Limb Amputees and Diabetes, run by VA Office of Research and Development at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 21 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Hamid Charkhkar, PhD ((216) 791-3800 ext. 62924, Hamid.Charkhkar@va.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cutaneous Vascular Conductance (time frame: baseline and visits 1-15 until study completion, average 1 year). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Aug 2026.