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

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

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.

Study Overview

• Status: Completed
• Conditions: Critical Limb Ischemia; Buerger's Disease
• Intervention / Treatment: Biological: Allogeneic Mesenchymal Stem Cells; Biological: Allogeneic Mesenchymal Stem Cells

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 2

Contacts and Locations

Study Locations

• India
  • Delhi
    • New Delhi, Delhi, India, 110029
      • Department of Surgical Disciplines, All India Institute of Medical Sciences
  • Haryana
    • Gurgaon, Haryana, India, 122001
      • Division of Peripheral Vascular and Endovascular Sciences, Medanta - The Medicity
  • Karnataka
    • Bangalore, Karnataka, India, 560066
      • Department of Vascular and Endovascular Surgery, M. S. Ramaiah Medical College and Hospitals
    • Bangalore, Karnataka, India, 560069
      • Peripheral Vascular Surgery, Sri Jayadeva Institute of Cardiovascular Sciences & Research
    • Mangalore, Karnataka, India, 575001
      • Department of Surgery, KMC, Mangalore
  • Tamil Nadu
    • Chennai, Tamil Nadu, India, 600003
      • Department of Vascular Surgery, Madras Medical College
    • Chennai, Tamil Nadu, India, 600116
      • Department of Vascular Surgery, Sri Ramchandra Medical College
    • Chennai, Tamil Nadu, India, 91-44-24732266
      • Department of Vascular Surgery, Stanley Medical College
  • West Bengal
    • Kolkata, West Bengal, India, 700029
      • Department of Vascular Surgery, AMRI Hospital
    • Kolkata, West Bengal, India, 700071
      • Nightingale Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Low dose; Stempeucel - CLI will be administered at the lowest dose	Biological: Allogeneic Mesenchymal Stem Cells; Single intramuscular administration of low dose of stem cells; Other Names: Stempeucel - CLI; Biological: Allogeneic Mesenchymal Stem Cells; Single intramuscular administration of intermediate dose of stem cells; Other Names: Stempeucel - CLI
EXPERIMENTAL: Intermediate dose; Stempeucel - CLI will be administered at intermediate dose	Biological: Allogeneic Mesenchymal Stem Cells; Single intramuscular administration of low dose of stem cells; Other Names: Stempeucel - CLI; Biological: Allogeneic Mesenchymal Stem Cells; Single intramuscular administration of intermediate dose of stem cells; Other Names: Stempeucel - CLI
NO_INTERVENTION: Control arm; Standard protocol of care alone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relief of the rest pain	Rest pain will be measured using rest pain scale (0 to10)	6 months
Healing of ulcerations or reduction of ulcer area in the target limb	Complete ulcer healing defined as complete epithelisation of ulcer and partial ulcer healing as at least 30% decrease in ulcer size.	6 months
Relief of the rest pain	Rest pain will be measured using rest pain scale (0 to 10)	24 months
Healing of ulcerations or reduction of ulcer area in the target limb	Complete ulcer healing defined as complete epithelisation of ulcer and partial ulcer healing as at least 30% decrease in ulcer size.	24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Pain free walking distance	6 and 24 months
Major amputation free survival	6 and 24 months
Ankle brachial pressure index (ABPI) - measured by Doppler	6 and 24 months
Increase in transcutaneous partial oxygen pressure (TcPO2)	6 and 24 months
Quality of life by King's College VascuQOL questionnaire	6 and 24 months
Angiogenesis - collateral blood vessels by Magnetic resonance angiogram (MRA)	6 and 24 months
The type of adverse events AE(s), number of AE(s) and proportion of patients with AE(s).	6 and 24 months
Assessment of clinical laboratory parameters	6 and 24 months
Physical examination findings and assessment of vital signs	6 and 24 months
Assessment of electrocardiogram (ECG) parameters	6 and 24 months

Collaborators and Investigators

• Sponsor: Stempeutics Research Pvt Ltd
• Investigators: Principal Investigator: Dr Anirban Chatterjee, AMRI Hospital; Principal Investigator: Dr Anita Dhar, All India Institute of Medical Sciences, New Delhi; Principal Investigator: Dr Rajkumar M, Stanley Medical College; Principal Investigator: Dr Radhakrishnan R, Sri Ramchandra Medical College; Principal Investigator: Dr Vidyasagaran T, Madras Medical College; Principal Investigator: Dr Alfred Augustine, KMC, Mangalore; Principal Investigator: Dr Sanjay Desai, M. S. Ramaiah Medical College; Principal Investigator: Dr Rajiv Parakh, Medanta - The Medicity; Principal Investigator: Dr Santanu Dutta, Nightingale Hospital; Principal Investigator: Dr Murali Krishna, Sri Jayadeva Institute of Cardiovascular Sciences & Research

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (ACTUAL): February 1, 2014
• Study Completion (ACTUAL): March 1, 2016

Study Registration Dates

• First Submitted: November 27, 2011
• First Submitted That Met QC Criteria: December 1, 2011
• First Posted (ESTIMATE): December 2, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): September 13, 2016
• Last Update Submitted That Met QC Criteria: September 12, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: Critical limb ischemia; Buerger's disease; Critical limb ischemia due to Buerger's disease
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Arterial Occlusive Diseases; Vasculitis; Ischemia; Thromboangiitis Obliterans
• Other Study ID Numbers: SRPL/CLI/10-11/001