Clinical trial NCT01353937: Endogenous Progenitors Cell Therapy for Diabetic Foot Ulcers
Official title: Endogenous Progenitors Cell Therapy for Diabetic Foot Ulcers
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Diabetic Ulcer
Keywords: wound healing
Lead sponsor: NYU Langone Health
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: Genzyme, a Sanofi Company
First posted: 2011-05-16
Enrollment: 0
Sex: ALL
Minimum age (years): 35
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Diabetic foot ulcers, a complication of diabetes leading to 80.000 lower limb amputations annually in the US, are a significant burden to our health system, costing more than a billion dollars annually. Here, we propose a novel combination of two drugs (Mozobil® and Regranex®Gel) to mobilize a specific sub-type of stem cells (endothelial progenitor cells) from the bone marrow and traffic them toward the wound, increasing the blood supply that subsequently improves wound healing. Because we are using the human body's own resources to regenerate itself by targeting and correcting the underlying pathophysiology, we believe that this novel therapy yields great promise in the treatment of diabetic foot ulcers.

Detailed description: Because diabetes impairs wound healing by altering fibroblast function, promotes chronic infection and diminishes blood supply to the skin, the lifetime risk of a person with diabetes developing a diabetic foot ulcer (DFU) is as high as 25%. Current strategies focus independently on the fibroblast dysfunction (growth factors such as PDGF/Regranex® Gel), on the chronic infection (debridement, antibacterial dressings) or on the blood supply (VAC®).

This project is different from the other projects because we propose to combine two drugs in a dual approach to first improve the fibroblast function using PDGF/Regranex® Gel and second to induce neovascularization in DFU by recruiting progenitor cells into the wound through a combination therapy of subcutaneous AMD3100 (Plerixafor/Mozobil®) with topical PDGF/Regranex® Gel. By contrast to novel stem cell therapies where cells are extracted, processed ex vivo and engrafted into the wound (exogenous stem cell therapy), here we propose to keep the stem cells in vivo (endogenous stem cell therapy).

Specifically, the first aim of the study will be to launch a prospective evaluator-blind pilot phase I/II safety and efficacy study to evaluate the clinical effect of AMD3100 (Plerixafor/Mozobil®) treatment with topical PDGF/Regranex® Gel compared to historical controls (standard of care and PDGF). AMD3100 (240 µg/kg SC) will be administered daily for 2 weeks. Our primary endpoint will be the measure of the percentage of change in area of the wound at 4 weeks (surrogate endpoint). In a second aim, we will measure the effect of AMD3100 treatment with PDGF using a quality-of-life index dedicated to DFU (DFS-SF).

Because we are addressing the underlying physiopathology in a dual approach, because we are avoiding the need for ex vivo processing and because both drugs are FDA approved, we believe that this novel therapy yields great promise in the treatment of DFUs.

Eligibility criteria: Inclusion Criteria:

1. Insulin-dependant type 2 diabetic patients
2. Age between 35 and 60 years-old
3. HbA1C between 6 and 12%
4. Full-thickness diabetic neuropathic foot ulcers
5. ≥ 2 weeks duration
6. Following standard of care débridement, ulcer size must be between 1 and 6 cm2
7. Adequate perfusion, defined as either transcutaneous oxygen measurements on the dorsum of the foot \>30 mmHg or ankle brachial indexes 0.7\<ABI\<1.2, as well as toe pressure \>30 mmHg.

Exclusion Criteria:

1. Clinical infection at the studied ulcer site (bacterial and fungal)
2. Clinically significant lower-extremity ischemia (as defined by an ankle/brachial index of \<0.65)
3. Active Charcot's foot as determined by clinical and radiographic examination
4. Ulcer of a non-diabetic pathophysiology (e.g., rheumatoid, radiation-related, and vasculitis-related ulcers, and especially venous stasis ulcer)
5. Significant medical conditions that would impair wound healing will also be excluded from the study. These conditions include liver disease, aplastic anemia, scleroderma and malignancy, treatment with immunosuppressive agents or steroids, myocardial infarcts, stroke, major surgery within 6 months of the study, usage of tobacco
6. Subjects with cancerous or pre-cancerous lesions in the area to be treated
7. Body weight \> 160 kg (because of Plerixafor's pharmacokinetic limitation)
8. Severe renal dysfunction (creatinine clearance \< 50 ml/min)
9. Severe non-proliferative or proliferative diabetic retinopathy
10. Capillary blood glucose \>350

Primary outcomes:
measure: Rate of Wound Closure
timeFrame: 1 year
measure: Quality of Life
timeFrame: 4 weeks
Secondary outcomes:
measure: Glycosylated hemoglobin (HbA1C)
timeFrame: 4 weeks
measure: capillary blood glucose (ACCUCHEK Finger Stick)
timeFrame: 4 weeks
measure: Transcutaneous oxygen tension measurements on wound and 1 cm-radius periphery (Radiometer adult sensor)
timeFrame: 4 weeks
measure: Ankle-brachial index (ABI, Prestige sphygmomanometer and Summit doppler probe)
timeFrame: 4 weeks
measure: pain (Visual-Analog Scale)
timeFrame: 4 weeks
measure: temperature of surrounding skin in a 1 cm-radius around the DFU (TempTouch Dermal Thermometer)
timeFrame: 4 weeks
measure: sensation (Nk Pressure-Specified Sensory Device)
timeFrame: 4 weeks
measure: photogrammetry (Photoshop CS3, Adobe Systems)
timeFrame: 4 weeks
measure: glomerular filtration rate (GFR, estimated by 24 hr. urine creatinine measurement)
timeFrame: 4 weeks
measure: diabetic retinopathy (digital ophthalmologic examination)
timeFrame: 4 weeks
measure: cEPCs by FACS analysis
timeFrame: 4 weeks
Other outcomes:
Locations:
city: New York
country: United States
facility: Helen L. & Martin S. Kimmel Wound Healing Center at the NYU Hospital for Joint Diseases
state: New York
Study officials:
affiliation: NYU Langone Health
name: Stephen Warren, MD
role: PRINCIPAL_INVESTIGATOR
References: