Diabetes, Lower Limb Amputees
Conditions
Keywords
lower extremity limb loss, Diabetes
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.
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.
Interventions
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.
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.
Sponsors
VA Office of Research and Development
Case Western Reserve University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cutaneous Vascular Conductance | 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 | 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 | 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 | 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 | baseline and visits 1-15 until study completion, average 1 year | From photoacoustic imaging, hemoglobin oxygenation is derived and compared across different study conditions |
Countries
United States
Contacts
CONTACTHamid Charkhkar, PhD
CONTACTJessica R Jarvela, MS BS
PRINCIPAL_INVESTIGATORHamid Charkhkar, PhD
Louis Stokes VA Medical Center, Cleveland, OH
Outcome results
None listed