Endogenous Progenitors Cell Therapy for Diabetic Foot Ulcers

NCT ID: NCT01353937

Last Updated: 2016-03-04

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-04-30
• Study Completion Date: 2016-09-30

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.

Conditions

Diabetic Ulcer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Standard of Care

All patients will be receiving the Standard of Care treatments regardless of whether or not they are receiving study drug.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Novel Combination Therapy

AMD3100 (Plerixafor) injection with Regranex Gel topical application

Group Type: ACTIVE_COMPARATOR

AMD3100 injection + rhPDGF-BB topical

Intervention Type: DRUG

drug therapy to be given for the first 2 week duration given on a daily basis initiated during the first visit (Day 0).

Becaplermin (Regranex Gel)

Topical application

Group Type: ACTIVE_COMPARATOR

AMD3100 injection + rhPDGF-BB topical

Intervention Type: DRUG

drug therapy to be given for the first 2 week duration given on a daily basis initiated during the first visit (Day 0).

Interventions

AMD3100 injection + rhPDGF-BB topical

drug therapy to be given for the first 2 week duration given on a daily basis initiated during the first visit (Day 0).

Intervention Type: DRUG

Other Intervention Names

AMD3100 (Plerixafor); rhPDGF-BB (Becaplermin); Regranex Gel

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

• Minimum Eligible Age: 35 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

Genzyme, a Sanofi Company

INDUSTRY

Sponsor Role: collaborator

NYU Langone Health

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stephen Warren, MD

Role: PRINCIPAL_INVESTIGATOR

NYU Langone Health

Locations

Helen L. & Martin S. Kimmel Wound Healing Center at the NYU Hospital for Joint Diseases

New York, New York, United States

Countries

United States

Other Identifiers

10-02116

Identifier Type: -

Identifier Source: org_study_id