Back to results

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

Primary Purpose

Critical Limb Ischemia, Buerger's Disease

Status

Completed

Phase

Phase 2

Locations

India

Study Type

Interventional

Intervention

Allogeneic Mesenchymal Stem Cells

About this trial

This is an interventional treatment trial for Critical Limb Ischemia focused on measuring Critical limb ischemia, Buerger's disease, Critical limb ischemia due to Buerger's disease

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Department of Surgical Disciplines, All India Institute of Medical Sciences
Division of Peripheral Vascular and Endovascular Sciences, Medanta - The Medicity
Department of Vascular and Endovascular Surgery, M. S. Ramaiah Medical College and Hospitals
Peripheral Vascular Surgery, Sri Jayadeva Institute of Cardiovascular Sciences & Research
Department of Surgery, KMC, Mangalore
Department of Vascular Surgery, Madras Medical College
Department of Vascular Surgery, Sri Ramchandra Medical College
Department of Vascular Surgery, Stanley Medical College
Department of Vascular Surgery, AMRI Hospital
Nightingale Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

No Intervention

Arm Label

Low dose

Intermediate dose

Control arm

Arm Description

Stempeucel - CLI will be administered at the lowest dose

Stempeucel - CLI will be administered at intermediate dose

Standard protocol of care alone

Outcomes

Primary Outcome Measures

Relief of the rest pain

Rest pain will be measured using rest pain scale (0 to10)

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.

Relief of the rest pain

Rest pain will be measured using rest pain scale (0 to 10)

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.

Secondary Outcome Measures

Pain free walking distance

Major amputation free survival

Ankle brachial pressure index (ABPI) - measured by Doppler

Increase in transcutaneous partial oxygen pressure (TcPO2)

Quality of life by King's College VascuQOL questionnaire

Angiogenesis - collateral blood vessels by Magnetic resonance angiogram (MRA)

The type of adverse events AE(s), number of AE(s) and proportion of patients with AE(s).

Assessment of clinical laboratory parameters

Physical examination findings and assessment of vital signs

Assessment of electrocardiogram (ECG) parameters

Full Information

NCT ID

NCT01484574

First Posted

November 27, 2011

Last Updated

September 12, 2016

Sponsor

Stempeutics Research Pvt Ltd

1. Study Identification

Unique Protocol Identification Number

NCT01484574

Brief Title

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

2. Study Status

Record Verification Date

September 2016

Overall Recruitment Status

Completed

Study Start Date

January 2012 (undefined)

Primary Completion Date

February 2014 (Actual)

Study Completion Date

March 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Stempeutics Research Pvt Ltd

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Critical Limb Ischemia, Buerger's Disease

Keywords

Critical limb ischemia, Buerger's disease, Critical limb ischemia due to Buerger's disease

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

90 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Low dose

Arm Type

Experimental

Arm Description

Stempeucel - CLI will be administered at the lowest dose

Arm Title

Intermediate dose

Arm Type

Experimental

Arm Description

Stempeucel - CLI will be administered at intermediate dose

Arm Title

Control arm

Arm Type

No Intervention

Arm Description

Standard protocol of care alone

Intervention Type

Biological

Intervention Name(s)

Allogeneic Mesenchymal Stem Cells

Other Intervention Name(s)

Stempeucel - CLI

Intervention Description

Single intramuscular administration of low dose of stem cells

Intervention Type

Biological

Intervention Name(s)

Allogeneic Mesenchymal Stem Cells

Other Intervention Name(s)

Stempeucel - CLI

Intervention Description

Single intramuscular administration of intermediate dose of stem cells

Primary Outcome Measure Information:

Title

Relief of the rest pain

Description

Rest pain will be measured using rest pain scale (0 to10)

Time Frame

6 months

Title

Healing of ulcerations or reduction of ulcer area in the target limb

Description

Complete ulcer healing defined as complete epithelisation of ulcer and partial ulcer healing as at least 30% decrease in ulcer size.

Time Frame

6 months

Title

Relief of the rest pain

Description

Rest pain will be measured using rest pain scale (0 to 10)

Time Frame

24 months

Title

Healing of ulcerations or reduction of ulcer area in the target limb

Description

Complete ulcer healing defined as complete epithelisation of ulcer and partial ulcer healing as at least 30% decrease in ulcer size.

Time Frame

24 months

Secondary Outcome Measure Information:

Title

Pain free walking distance

Time Frame

6 and 24 months

Title

Major amputation free survival

Time Frame

6 and 24 months

Title

Ankle brachial pressure index (ABPI) - measured by Doppler

Time Frame

6 and 24 months

Title

Increase in transcutaneous partial oxygen pressure (TcPO2)

Time Frame

6 and 24 months

Title

Quality of life by King's College VascuQOL questionnaire

Time Frame

6 and 24 months

Title

Angiogenesis - collateral blood vessels by Magnetic resonance angiogram (MRA)

Time Frame

6 and 24 months

Title

The type of adverse events AE(s), number of AE(s) and proportion of patients with AE(s).

Time Frame

6 and 24 months

Title

Assessment of clinical laboratory parameters

Time Frame

6 and 24 months

Title

Physical examination findings and assessment of vital signs

Time Frame

6 and 24 months

Title

Assessment of electrocardiogram (ECG) parameters

Time Frame

6 and 24 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

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

Overall Study Officials: