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

Critical Limb Ischemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01484574
• Other study ID #: SRPL/CLI/10-11/001
• Status: Completed
• Phase: Phase 2
• First received: November 27, 2011
• Last updated: September 12, 2016
• Start date: January 2012
• Est. completion date: March 2016

Study information

• Verified date: September 2016
• Source: Stempeutics Research Pvt Ltd
• Contact: n/a
• Is FDA regulated: No
• Health authority: India: Drugs Controller General of India
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: March 2016
• Est. primary completion date: February 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Buerger's Disease
• Critical Limb Ischemia
• Ischemia
• Thromboangiitis Obliterans

Intervention

Biological:
• Allogeneic Mesenchymal Stem Cells
Single intramuscular administration of low dose of stem cells
• Allogeneic Mesenchymal Stem Cells
Single intramuscular administration of intermediate dose of stem cells

Locations

Country	Name	City	State
India	Department of Vascular and Endovascular Surgery, M. S. Ramaiah Medical College and Hospitals	Bangalore	Karnataka
India	Peripheral Vascular Surgery, Sri Jayadeva Institute of Cardiovascular Sciences & Research	Bangalore	Karnataka
India	Department of Vascular Surgery, Madras Medical College	Chennai	Tamil Nadu
India	Department of Vascular Surgery, Sri Ramchandra Medical College	Chennai	Tamil Nadu
India	Department of Vascular Surgery, Stanley Medical College	Chennai	Tamil Nadu
India	Division of Peripheral Vascular and Endovascular Sciences, Medanta - The Medicity	Gurgaon	Haryana
India	Department of Vascular Surgery, AMRI Hospital	Kolkata	West Bengal
India	Nightingale Hospital	Kolkata	West Bengal
India	Department of Surgery, KMC, Mangalore	Mangalore	Karnataka
India	Department of Surgical Disciplines, All India Institute of Medical Sciences	New Delhi	Delhi

Sponsors (1)

Lead Sponsor	Collaborator
Stempeutics Research Pvt Ltd

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Relief of the rest pain	Rest pain will be measured using rest pain scale (0 to10)	6 months	No
Primary	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	No
Primary	Relief of the rest pain	Rest pain will be measured using rest pain scale (0 to 10)	24 months	No
Primary	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	No
Secondary	Pain free walking distance		6 and 24 months	No
Secondary	Major amputation free survival		6 and 24 months	No
Secondary	Ankle brachial pressure index (ABPI) - measured by Doppler		6 and 24 months	No
Secondary	Increase in transcutaneous partial oxygen pressure (TcPO2)		6 and 24 months	No
Secondary	Quality of life by King's College VascuQOL questionnaire		6 and 24 months	No
Secondary	Angiogenesis - collateral blood vessels by Magnetic resonance angiogram (MRA)		6 and 24 months	No
Secondary	The type of adverse events AE(s), number of AE(s) and proportion of patients with AE(s).		6 and 24 months	Yes
Secondary	Assessment of clinical laboratory parameters		6 and 24 months	Yes
Secondary	Physical examination findings and assessment of vital signs		6 and 24 months	Yes
Secondary	Assessment of electrocardiogram (ECG) parameters		6 and 24 months	Yes