Clinical trial NCT01686139: Safety Study of Stem Cells Treatment in Diabetic Foot Ulcers
Official title: Phase 1 Study: Treatment of Patients With Diabetic Foot Complications With Allogeneic Bone Marrow Derived Mesenchymal Stromal Cells (ABMD-MSC)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Type I Diabetes Mellitus With Ulcer
Type II Diabetes Mellitus With Ulcer
Keywords: Diabetic mellitus
Diabetic foot ulcers
Ischemic Limb
Lead sponsor: Sheba Medical Center
Sponsor class: OTHER_GOV
First posted: 2012-09-17
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 81
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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.

Primary outcomes:
measure: Frequency of Adverse Events
timeFrame: 6 months after treatment
Secondary outcomes:
Other outcomes:
Locations:
city: Ramat Gan
country: Israel
facility: Orthopedic Rehabilitation out-patient clinic, Sheba Medical Center
Study officials:
affiliation: Sheba Medical Center
name: Itzhak Siev-Ner, MD
role: PRINCIPAL_INVESTIGATOR
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