Endogenous Progenitors Cell Therapy for Diabetic Foot Ulcers
| Status: | Withdrawn |
|---|---|
| Conditions: | Gastrointestinal, Podiatry, Diabetes |
| Therapuetic Areas: | Endocrinology, Gastroenterology, Orthopedics / Podiatry |
| Healthy: | No |
| Age Range: | 35 - 60 |
| Updated: | 4/21/2016 |
| Start Date: | April 2014 |
| End Date: | September 2016 |
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.
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.
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.
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.
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
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
We found this trial at
1
site
New York, New York 10003
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