Clinical trial NCT01484574: A Clinical Trial to Study the Efficacy and Safety of Different Doses of Bone Marrow Derived Mesenchymal Stem Cells in Patients With Critical Limb Ischemia Due to Buergers Disease
Official title: A Non-randomized, Open Label, Multicentric, Dose Ranging , Phase II Study Assessing the Efficacy and Safety of Intramuscular Administration of Stempeucel - CLI™ (ex Vivo Cultured Adult Bone Marrow Derived Allogeneic Mesenchymal Stem Cells) in Patients With Critical Limb Ischemia Due to Buerger's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Critical Limb Ischemia
Buerger's Disease
Keywords: Critical limb ischemia
Buerger's disease
Critical limb ischemia due to Buerger's disease
Lead sponsor: Stempeutics Research Pvt Ltd
Sponsor class: INDUSTRY
First posted: 2011-12-02
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is an open label, non-randomized, dose ranging study to evaluate the safety and efficacy of different doses of Stempeucel in critical limb ischemia patients.


Eligibility criteria: Inclusion Criteria:

* Buerger's disease as diagnosed by Shionoya criteria
* Males or females (willing to use accepted methods of contraception during the course of the study) in the age group of 18-65 yrs
* Established CLI in the study limb, clinically and hemodynamically confirmed as per Rutherford- III-5
* Patients in Rutherford- III-6 if gangrene extending maximally up to the head of metatarsal but limited to toes (Patients with wet gangrene must undergo wound debridement / amputation before screening)
* Patients having infrapopliteal occlusive disease with rest pain and ischemic ulcer/necrosis, who are not eligible for or have failed traditional revascularization treatment as per the investigators judgment (No option patients)
* Ankle Brachial Pressure Index (ABPI) ≤ 0.6 or ankle pressure ≤ 50 mm Hg or TcPO2 ≤ 40 mmHg in the foot of the study limb
* Patients who are able to understand the requirements of the study, and willing to provide voluntary written informed consent and video consent, abide by the study requirements, and agree to return for required follow-up visits

Exclusion Criteria:

* Patients with CLI indicated for major amputation during screening
* Atherosclerotic PAD
* Ulcers with exposure of tendon and/bone in the shin region
* Previous above transmetatarsal amputation in study limb
* Any Lumbar sympathectomy procedure performed less than 90 days prior to the screening
* Patients with gait disturbance for reasons other than CLI
* Diagnosis of diabetes mellitus (type 1 or type 2)
* Patients having left ventricular ejection fraction \< 35%
* Patients suffering from clinically relevant peripheral neuropathy
* History of Stroke or myocardial infarction
* Patients who are contraindicated for MRA
* Patients with deep vein thrombosis in any limb
* Patients who have clinically serious and/or unstable inter-current infection, medical illnesses or conditions that are uncontrolled or whose control, in the opinion of the Investigator, may be jeopardized by participation in this study or by the complications of this therapy
* Documented terminal illness or cancer or any concomitant disease process with a life expectancy of \<1 year
* Patients already enrolled in another investigational drug trial or completed within 3 months or those who have participated in any stem cell clinical trial
* Patient with known hypersensitivity to the constituents of the IMP - dimethyl sulfoxide (DMSO) or human serum albumin (HSA)
* History of severe alcohol or drug abuse within 3 months of screening
* Hb% \< 10 gm% for males, Hb% \< 9 gm% for females, serum creatinine ≥ 2mg%, serum Total Bilirubin ≥2mg%
* Pregnant and lactating women
* Patients tested positive for HIV 1, HCV, HBV, CMV, RPR

Primary outcomes:
measure: Relief of the rest pain
timeFrame: 6 months
measure: Healing of ulcerations or reduction of ulcer area in the target limb
timeFrame: 6 months
measure: Relief of the rest pain
timeFrame: 24 months
measure: Healing of ulcerations or reduction of ulcer area in the target limb
timeFrame: 24 months
Secondary outcomes:
measure: Pain free walking distance
timeFrame: 6 and 24 months
measure: Major amputation free survival
timeFrame: 6 and 24 months
measure: Ankle brachial pressure index (ABPI) - measured by Doppler
timeFrame: 6 and 24 months
measure: Increase in transcutaneous partial oxygen pressure (TcPO2)
timeFrame: 6 and 24 months
measure: Quality of life by King's College VascuQOL questionnaire
timeFrame: 6 and 24 months
measure: Angiogenesis - collateral blood vessels by Magnetic resonance angiogram (MRA)
timeFrame: 6 and 24 months
measure: The type of adverse events AE(s), number of AE(s) and proportion of patients with AE(s).
timeFrame: 6 and 24 months
measure: Assessment of clinical laboratory parameters
timeFrame: 6 and 24 months
measure: Physical examination findings and assessment of vital signs
timeFrame: 6 and 24 months
measure: Assessment of electrocardiogram (ECG) parameters
timeFrame: 6 and 24 months
Other outcomes:
Locations:
city: New Delhi
country: India
facility: Department of Surgical Disciplines, All India Institute of Medical Sciences
state: Delhi
city: Gurgaon
country: India
facility: Division of Peripheral Vascular and Endovascular Sciences, Medanta - The Medicity
state: Haryana
city: Bangalore
country: India
facility: Department of Vascular and Endovascular Surgery, M. S. Ramaiah Medical College and Hospitals
state: Karnataka
city: Bangalore
country: India
facility: Peripheral Vascular Surgery, Sri Jayadeva Institute of Cardiovascular Sciences & Research
state: Karnataka
city: Mangalore
country: India
facility: Department of Surgery, KMC, Mangalore
state: Karnataka
city: Chennai
country: India
facility: Department of Vascular Surgery, Madras Medical College
state: Tamil Nadu
city: Chennai
country: India
facility: Department of Vascular Surgery, Sri Ramchandra Medical College
state: Tamil Nadu
city: Chennai
country: India
facility: Department of Vascular Surgery, Stanley Medical College
state: Tamil Nadu
city: Kolkata
country: India
facility: Department of Vascular Surgery, AMRI Hospital
state: West Bengal
city: Kolkata
country: India
facility: Nightingale Hospital
state: West Bengal
Study officials:
affiliation: AMRI Hospital
name: Dr Anirban Chatterjee
role: PRINCIPAL_INVESTIGATOR
affiliation: All India Institute of Medical Sciences
name: Dr Anita Dhar
role: PRINCIPAL_INVESTIGATOR
affiliation: Stanley Medical College
name: Dr Rajkumar M
role: PRINCIPAL_INVESTIGATOR
affiliation: Sri Ramchandra Medical College
name: Dr Radhakrishnan R
role: PRINCIPAL_INVESTIGATOR
affiliation: Madras Medical College
name: Dr Vidyasagaran T
role: PRINCIPAL_INVESTIGATOR
affiliation: KMC, Mangalore
name: Dr Alfred Augustine
role: PRINCIPAL_INVESTIGATOR
affiliation: M. S. Ramaiah Medical College
name: Dr Sanjay Desai
role: PRINCIPAL_INVESTIGATOR
affiliation: Medanta - The Medicity
name: Dr Rajiv Parakh
role: PRINCIPAL_INVESTIGATOR
affiliation: Nightingale Hospital
name: Dr Santanu Dutta
role: PRINCIPAL_INVESTIGATOR
affiliation: Sri Jayadeva Institute of Cardiovascular Sciences & Research
name: Dr Murali Krishna
role: PRINCIPAL_INVESTIGATOR
References: