Diabetic Foot, Diabetic Peripheral Neuropathy
Conditions
Brief summary
This is an interventional open-label study to determine the safety and clinical performance of SVF cells in the treatment of Diabetic Peripheral Neuropathy.
Detailed description
The burden of diabetes mellitus (DM) is a global socio-economic burdern affecting an estimate 578 million (M) people by 2030 and consuming 10% of world health care expenditures. Sequelae of diabetes are seen in the distal extremities, the most common being peripheral neuropathy (DPN) affecting up to 50% of patients within the first 10 years of the disease. Painful neuropathy is present in 20-30% of patients and is resistant to pharmaceutical treatments such as tricyclics antidepressants, anticonvulsants, serotonin reuptake inhibitors, and opioids. No FDA-approved therapies with disease-modifying activity currently exist. In over 50% of patients DPN follows a progressive course characterized initially by loss of pedal sensation, predisposing to failure to perceive traumatic injuries with consequent ulceration and the threat of limb loss. Several types of adult derived mesenchymal sromal/stem (sic) cells have been used for the treatment of DFUs with varied results based on their anti-inflammatory, anti-fibrotic and tissue repair properties. Adipose tissue provides a readily accessible sources of MSCs; these cells can be isolated from the adipose structural components after liposuction and subsequently cultured. Drawbacks of AD-MSCs include the cost of Good Manufacturing Practice culure/manufacturing, time of manufacturing and potential allergic reactions, if the cell prduct comes from an allogeneic source. An alternative to cultured/manufactured AD-MSC is an AD-MSC containing product, stromal vascular fraction (SVF), that can be obtained and delivered as a point-of-care intervention. SVF has been shown to secrete numerous growth factors and cytokines, including vascular endothelial growth factor, transforming growth factor-1 and hepatocyte growth factor, and interferon-gamma and IL-10. In addition, SVF has been shown to induce M2 macrophages, further driving an anti-inflammatory environment. SVF has been used in multiple clinical trials to treat diabetic foot ulcers, peripheral vascular disease, burn wounds, radiation injury and Crohn's disease fistula, among other disease states. SVF has been used in the United States under a Food and Drug Administration investigational device exemption to treat knee osteoarthritis (safe and with evidence of potential efficacy) and is currently in a pivotal clinical trial ("150 subjects) for that indication. In previous publications regarding treatment of chronic wounds due to diabetes and ischemia anecdotal evidence of long-term improvements in sensation were noted. For this reason this additional study was designed to investigate the clinical of using SVF cells for the treatment of DPN.
Interventions
Administration to the DFU / ankle was performed at four injection sites: 1. 20 cc into the wound bed 2. 20 cc subcutaneously around the perimeter of the wound 3. 10 cc along the tibialis posterior pathway at the ankle prior to entry into the plantar surface 4. 10 cc along the tibialis anterior / dorsalis pedis pathway from the ankle to the dorsum of the foot.
Sponsors
Michael H Carstens
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Clinically stable diabetes * Presence of DPN as documented reductions in sensory perception threshold (SPT) and/or vibration perception threshold below protective levels * Capacity to understand and provide informed consent.
Exclusion criteria
* Presence of a disease prohibitive of surgical intervention * Smoking and/or substance abuse within 3 months of the onset of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Foot Ulcer Healing | Baseline, 4, 12, 24, and 48 weeks post treatment. | Percent closure based on changes in ulcer size dimensions in square cm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fine Touch Sensation: Documenting diabetes-associated lower extremity pathophysiology changes | Baseline, 4, 12, 24, and 48 weeks post treatment. | Semmes-Weinstein scores to document sensation threshold |
| Vibration: Documenting diabetes-associated lower extremity pathophysiology changes | Baseline, 4, 12, 24, and 48 weeks post treatment. | Horwell neurothesiometer scores to document vibration threshold |
Countries
Nicaragua
Contacts
STUDY_DIRECTORKenneth A Bertram, MD, PhD
Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC, USA
PRINCIPAL_INVESTIGATORMichael H Carstens, MD
Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC, USA
Outcome results
None listed