Endogenous Progenitors Cell Therapy for Diabetic Foot Ulcers (AMD3100)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified May 2011 by New York University School of Medicine
Sponsor:
Collaborators:
Genzyme, a Sanofi Company
Information provided by (Responsible Party):
Stephen Warren, New York University School of Medicine
ClinicalTrials.gov Identifier:
NCT01353937
First received: May 12, 2011
Last updated: April 25, 2013
Last verified: May 2011
  Purpose

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.


Condition Intervention Phase
Diabetic Ulcer
Drug: AMD3100 injection + rhPDGF-BB topical
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: Endogenous Progenitors Cell Therapy for Diabetic Foot Ulcers

Resource links provided by NLM:


Further study details as provided by New York University School of Medicine:

Primary Outcome Measures:
  • Rate of Wound Closure [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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.

  • Quality of Life [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Glycosylated hemoglobin (HbA1C) [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
    long-term measure of diabetes control

  • capillary blood glucose (ACCUCHEK Finger Stick) [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
    short-term measure of diabetes control

  • Transcutaneous oxygen tension measurements on wound and 1 cm-radius periphery (Radiometer adult sensor) [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
    non-invasive measure of skin circulation

  • Ankle-brachial index (ABI, Prestige sphygmomanometer and Summit doppler probe) [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
    measure of peripheral vascular disease

  • pain (Visual-Analog Scale) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    measure of the subjective symptom of pain

  • temperature of surrounding skin in a 1 cm-radius around the DFU (TempTouch Dermal Thermometer) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    to identify increased skin temperatures, intended as an early warning of inflammation, impending infection, and possible foot ulceration.

  • sensation (Nk Pressure-Specified Sensory Device) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Quantification of sensory nerve function in patients with symptoms of, or the potential for, neurologic damage or disease

  • photogrammetry (Photoshop CS3, Adobe Systems) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    used to document wound appearance

  • glomerular filtration rate (GFR, estimated by 24 hr. urine creatinine measurement) [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
    to estimate renal function

  • diabetic retinopathy (digital ophthalmologic examination) [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
    to evaluate for development of nonproliferative and proliferative retinopathy

  • cEPCs by FACS analysis [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    to measure the extent of BM EPC mobilization into the circulation and correlate the number cEPCs to other primary and secondary endpoints


Estimated Enrollment: 27
Study Start Date: April 2014
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   35 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01353937

Contacts
Contact: Stephen Warren, MD 212-263-3704 stephen.warren@nyumc.org

Locations
United States, New York
Helen L. & Martin S. Kimmel Wound Healing Center at the NYU Hospital for Joint Diseases Not yet recruiting
New York, New York, United States, 10003
Contact: Frank Ross, MD    212-263-7187    frank.ross@nyumc.org   
Sub-Investigator: Frank Ross, MD         
Sponsors and Collaborators
New York University School of Medicine
Genzyme, a Sanofi Company
Investigators
Principal Investigator: Stephen Warren, MD New York University School of Medicine
  More Information

No publications provided

Responsible Party: Stephen Warren, Associate Professor, New York University School of Medicine
ClinicalTrials.gov Identifier: NCT01353937     History of Changes
Other Study ID Numbers: 10-02116
Study First Received: May 12, 2011
Last Updated: April 25, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by New York University School of Medicine:
wound healing

Additional relevant MeSH terms:
Ulcer
Foot Ulcer
Diabetic Foot
Pathologic Processes
Foot Diseases
Skin Diseases
Leg Ulcer
Skin Ulcer
Diabetic Angiopathies
Vascular Diseases
Cardiovascular Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Diabetic Neuropathies
Platelet-derived growth factor BB
JM 3100
Angiogenesis Inducing Agents
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 27, 2014