Endogenous Progenitors Cell Therapy for Diabetic Foot Ulcers (AMD3100)

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.

Study Overview

• Status: Withdrawn
• Conditions: Diabetic Ulcer
• Intervention / Treatment: Drug: AMD3100 injection + rhPDGF-BB topical

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.

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10003
      • Helen L. & Martin S. Kimmel Wound Healing Center at the NYU Hospital for Joint Diseases

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 60 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
NO_INTERVENTION: Standard of Care; All patients will be receiving the Standard of Care treatments regardless of whether or not they are receiving study drug.
ACTIVE_COMPARATOR: Novel Combination Therapy; AMD3100 (Plerixafor) injection with Regranex Gel topical application	Drug: 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).; Other Names: AMD3100 (Plerixafor); rhPDGF-BB (Becaplermin); Regranex Gel
ACTIVE_COMPARATOR: Becaplermin (Regranex Gel); Topical application	Drug: 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).; Other Names: AMD3100 (Plerixafor); rhPDGF-BB (Becaplermin); Regranex Gel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Wound Closure	The safety and efficacy of AMD3100 (Plerixafor) with rhPDGF-BB (Becaplermin) compared to two historical treatments group (Beclapermin versus standard of care (SOC) treatment) for the treatment of DFUs.[21] The central hypothesis to be tested is that a novel combination therapy will significantly increase the rate of closure of DFUs as compared to historical treatments groups, while presenting no major side effect.	1 year
Quality of Life	Test whether patients treated with the novel combination therapy will have an improvement in their quality of life, with higher scores on the DFS-SF than those of the historical control groups.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glycosylated hemoglobin (HbA1C)	long-term measure of diabetes control	4 weeks
capillary blood glucose (ACCUCHEK Finger Stick)	short-term measure of diabetes control	4 weeks
Transcutaneous oxygen tension measurements on wound and 1 cm-radius periphery (Radiometer adult sensor)	non-invasive measure of skin circulation	4 weeks
Ankle-brachial index (ABI, Prestige sphygmomanometer and Summit doppler probe)	measure of peripheral vascular disease	4 weeks
pain (Visual-Analog Scale)	measure of the subjective symptom of pain	4 weeks
temperature of surrounding skin in a 1 cm-radius around the DFU (TempTouch Dermal Thermometer)	to identify increased skin temperatures, intended as an early warning of inflammation, impending infection, and possible foot ulceration.	4 weeks
sensation (Nk Pressure-Specified Sensory Device)	Quantification of sensory nerve function in patients with symptoms of, or the potential for, neurologic damage or disease	4 weeks
photogrammetry (Photoshop CS3, Adobe Systems)	used to document wound appearance	4 weeks
glomerular filtration rate (GFR, estimated by 24 hr. urine creatinine measurement)	to estimate renal function	4 weeks
diabetic retinopathy (digital ophthalmologic examination)	to evaluate for development of nonproliferative and proliferative retinopathy	4 weeks
cEPCs by FACS analysis	to measure the extent of BM EPC mobilization into the circulation and correlate the number cEPCs to other primary and secondary endpoints	4 weeks

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Collaborators: National Institutes of Health (NIH); Genzyme, a Sanofi Company
• Investigators: Principal Investigator: Stephen Warren, MD, NYU Langone Health

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (ANTICIPATED): March 1, 2016
• Study Completion (ANTICIPATED): September 1, 2016

Study Registration Dates

• First Submitted: May 12, 2011
• First Submitted That Met QC Criteria: May 12, 2011
• First Posted (ESTIMATE): May 16, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): March 4, 2016
• Last Update Submitted That Met QC Criteria: March 2, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: wound healing
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Endocrine System Diseases; Diabetic Angiopathies; Leg Ulcer; Skin Ulcer; Diabetes Complications; Diabetes Mellitus; Diabetic Neuropathies; Foot Diseases; Diabetic Foot; Foot Ulcer; Ulcer; Physiological Effects of Drugs; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Angiogenesis Modulating Agents; Growth Substances; Anticoagulants; Angiogenesis Inducing Agents; Plerixafor; Becaplermin
• Other Study ID Numbers: 10-02116