Endogenous Progenitors Cell Therapy for Diabetic Foot Ulcers

Diabetic Ulcer Clinical Trial

— AMD3100  

Official title:

Endogenous Progenitors Cell Therapy for Diabetic Foot Ulcers

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01353937
• Other study ID #: 10-02116
• Status: Withdrawn
• Phase: Phase 1
• First received: May 12, 2011
• Last updated: March 2, 2016
• Start date: April 2014
• Est. completion date: September 2016

Study information

• Verified date: March 2016
• Source: New York University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: September 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 35 Years to 60 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetic Foot
• Diabetic Ulcer
• Ulcer

Intervention

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).

Locations

Country	Name	City	State
United States	Helen L. & Martin S. Kimmel Wound Healing Center at the NYU Hospital for Joint Diseases	New York	New York

Sponsors (3)

Lead Sponsor	Collaborator
New York University School of Medicine	Genzyme, a Sanofi Company, National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Secondary	Glycosylated hemoglobin (HbA1C)	long-term measure of diabetes control	4 weeks	Yes
Secondary	capillary blood glucose (ACCUCHEK Finger Stick)	short-term measure of diabetes control	4 weeks	Yes
Secondary	Transcutaneous oxygen tension measurements on wound and 1 cm-radius periphery (Radiometer adult sensor)	non-invasive measure of skin circulation	4 weeks	Yes
Secondary	Ankle-brachial index (ABI, Prestige sphygmomanometer and Summit doppler probe)	measure of peripheral vascular disease	4 weeks	Yes
Secondary	pain (Visual-Analog Scale)	measure of the subjective symptom of pain	4 weeks	No
Secondary	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	No
Secondary	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	No
Secondary	photogrammetry (Photoshop CS3, Adobe Systems)	used to document wound appearance	4 weeks	No
Secondary	glomerular filtration rate (GFR, estimated by 24 hr. urine creatinine measurement)	to estimate renal function	4 weeks	Yes
Secondary	diabetic retinopathy (digital ophthalmologic examination)	to evaluate for development of nonproliferative and proliferative retinopathy	4 weeks	Yes
Secondary	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	No