Safety Study of Stem Cells Treatment in Diabetic Foot Ulcers

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified January 2014 by Sheba Medical Center
Sponsor:
Information provided by (Responsible Party):
Dr. Itzhak Siev-Ner, Sheba Medical Center
ClinicalTrials.gov Identifier:
NCT01686139
First received: September 12, 2012
Last updated: January 29, 2014
Last verified: January 2014
  Purpose

Diabetes Mellitus (DM) can be regarded as one of the "epidemics" of the western world.

DM contributes to severe morbidity and mortality due to damage in the target organs (neuropathy, vasculopathy, nephropathy, retinopathy).

It affects the quality of life of the patients because of increased rate of blindness, IHD, stroke, end stage renal failure, hemodialysis and lower limb amputations (LLA).The Diabetic Foot (DF) is defined as destruction or infection of tissue/s in the foot of diabetic patients due to neurological damage and / or different levels of Peripheral Vascular Disease (PVD). Diabetic foot complications are the most common cause of lower extremity amputations in the industrialized world. The lifetime occurence of Diabetic Foot Ulcers (DFU) is 20% in diabetic patients.

Between 15% - 25% of the foot ulcers will lead to lower limb amputations.

It has been shown that Mesenchymal Stem Cells (MSCs) could be an effective therapy for many diseases including acute respiratory distress syndrome, spinal cord injury, liver injury and critical limb ischemia.

Stem cells can be obtained from either the patient (autologous) or non-related healthy donors (allogeneic).

The purpose of this study is to determine the safety and efficacy of cultured Bone Marrow Mesenchymal Stromal Cells (BM-MSCs) from allogeneic donors for treatment of chronic leg wounds of diabetic patients.


Condition Intervention Phase
Type I Diabetes Mellitus With Ulcer
Type II Diabetes Mellitus With Ulcer
Biological: ABMD-MSC
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 1/2 Study: Treatment of Patients With Diabetic Foot Complications With Allogeneic Bone Marrow Derived Mesenchymal Stromal Cells (ABMD-MSC)

Resource links provided by NLM:


Further study details as provided by Sheba Medical Center:

Primary Outcome Measures:
  • Frequency of Adverse Events [ Time Frame: 6 months after treatment ] [ Designated as safety issue: Yes ]
    Frequency and severity of Adverse Events.


Secondary Outcome Measures:
  • Healing of all wounds in the target limb [ Time Frame: 6 months after treatment ] [ Designated as safety issue: No ]
    Healing of all wounds in the target limb (percentage of wound size reduction). Measurements of wound size and wound grading using the University of Texas Diabetic Wound Classification scale


Other Outcome Measures:
  • Reduced pain [ Time Frame: 6 months after treatment ] [ Designated as safety issue: No ]
    Reduced pain, measured by VAS scale and use of analgesics.


Estimated Enrollment: 10
Study Start Date: May 2014
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ABDM-MSC

The patient will receive multiple injections in one session during the study. The injections will take place in the chronic wound bed and in the third distal part of the treated shin (in the form of a ring).

Maximal amount of ABMD-MSC cells injected: 10-20*10^6 cells (up to volume of 20mL, depending on the wound size & patient weight).

Biological: ABMD-MSC
10-20 x 10^6 cells/20mL

  Eligibility

Ages Eligible for Study:   18 Years to 81 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient signed informed consent.
  • Adult males or females between 18 and 81 years of age with diabetes mellitus type 1 or type 2.
  • Patient has one Diabetic Foot Ulcer (DFU) on the treated leg. The size of the DFU is no greater than 10 cm2 .
  • The Diabetic Foot Ulcer (DFU) is neuropathic: The patient is checked by a 5.27 mm Monofilament, and doesn't have a sensation in at least 4 of 9 points in the foot.
  • No endovascular or surgical interventions are planned.
  • Patient isn't in an immediate life threat.
  • Normal organ and marrow function as defined:

    1. Leukocytes ≥3,000/μL
    2. Absolute neutrophil count ≥1,500/μL
    3. Platelets ≥140,000/μL
    4. AST (SGOT)/ALT (SGPT) ≤2.5 X institutional standards range
    5. Creatinine ≤ 2.5 mg/dL
  • Patients with controlled blood pressure (defined as a systolic blood pressure ≤180 and/or a diastolic blood pressure of ≤110 mmHg) and established anti-hypertensive therapy as necessary prior to entry into the study.

Exclusion Criteria:

  • Patient weight is greater than 120 Kg.
  • Patients with poorly controlled diabetes mellitus (HbA1c > 10%).
  • Presence of osteomyelitis (stage B grade 3 and stage D grade 3 on the UT Scale).
  • More than one ulcer in the treated foot.
  • Patients with a known failed ipsilateral revascularization procedure within 4 weeks prior to enrollment.
  • Patients with ABI <= 0.3
  • Patients receiving treatment with hematopoietic growth factors.
  • (Actively) infected ulcer.
  • Infection of the involved extremity(ies) in the intended region of injection. Patient will be included (injected) if there is a safe zone of 10 cm from any soft tissue infection, manifested by fever, purulence and severe cellulitis.
  • Active wet gangrenous tissue.
  • Patients who require uninterrupted anticoagulation or anti-platelet therapy [i.e. anticoagulation therapy (e.g. Coumadin) that cannot be stopped for 72 hours prior to intramuscular injections.
  • Patients with a blood clotting disorder not caused by medication.
  • Patients with known cancer undergoing treatment including chemotherapy, radiotherapy or immunotherapy.
  • Patients with end stage renal disease requiring dialysis.
  • Patients who are pregnant or lactating.
  • History of regular alcohol consumption exceeding 2 drinks/day (1 drink = 5 oz [150mL] of wine or 12 oz [360mL] of beer or 1.5 oz [45mL] of hard liquor) within 6 months of screening and/or history of illicit drug use.
  • Known allergies to protein products (horse or bovine serum, or porcine trypsin) used in the cell production process.
  • Patients receiving experimental medications or participating in another clinical study within 30 days of screening.
  • Immune deficient patients.
  • Patients with positive blood tests for Hepatitis B or Hepatitis C or HIV or Syphilis at the time of screening.
  • Patients treated by Ilomedin (Iloprost).
  • Patients having received a new chronic pharmacologic treatment regimen within 4 weeks prior to enrollment.
  • Patients undergoing hyperbaric oxygen treatment within 4 weeks of inclusion and/or required throughout the trial.
  • Concomitant wound treatments that include growth factors or tissue engineered products.
  • In the opinion of the investigator, the patient is unsuitable for cellular therapy.
  • Patients receiving systemic or direct target limb injection of antiangiogenic drugs.
  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: NCT01686139

Contacts
Contact: Miri Rosenhouse, B. Sc. 03-530-3701 miri.rosenhouse@gmail.com

Locations
Israel
Orthopedic Rehabilitation out-patient clinic, Sheba Medical Center Not yet recruiting
Ramat Gan, Israel
Contact: Miri Rosenhouse, B.Sc.    03-530-3701    miri.rosenhouse@gmail.com   
Principal Investigator: Itzhak Siev-Ner, MD         
Sponsors and Collaborators
Sheba Medical Center
Investigators
Principal Investigator: Itzhak Siev-Ner, MD Sheba Medical Center
  More Information

Publications:
Wu Y. et al., Concise review: Bone marrow derived stem/progenitor cells in cutaneous repair and regeneration. Stem Cells. 2010; 28:905-915.

Responsible Party: Dr. Itzhak Siev-Ner, Head of the Orthopedic Rehabilitation Department, Sheba Medical Center
ClinicalTrials.gov Identifier: NCT01686139     History of Changes
Other Study ID Numbers: SHEBA-11-8802-IS-SMC
Study First Received: September 12, 2012
Last Updated: January 29, 2014
Health Authority: Israel: Ministry of Health

Keywords provided by Sheba Medical Center:
Diabetic mellitus
Diabetic foot ulcers
Ischemic Limb

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Diabetes Mellitus, Type 2
Ulcer
Foot Ulcer
Diabetic Foot
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes
Foot Diseases
Skin Diseases
Leg Ulcer
Skin Ulcer
Diabetic Angiopathies
Vascular Diseases
Cardiovascular Diseases
Diabetes Complications
Diabetic Neuropathies

ClinicalTrials.gov processed this record on August 28, 2014