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Effectiveness and Safety of Adipose-Derived Regenerative Cells for the Treatment of Critical Lower Limb Ischemia

Primary Purpose

Critical Limb Ischemia, Arteriosclerosis Obliterans, Peripheral Arterial Disease

Status

Unknown status

Phase

Phase 1

Locations

Russian Federation

Study Type

Interventional

Intervention

ADRC injection

ADRC isolation

Liposuction

About this trial

This is an interventional treatment trial for Critical Limb Ischemia focused on measuring Critical lower limb ischemia, Atherosclerosis obliterans, Diabetic angiopathies, Thromboangiitis obliterans, Ischemic ulcers, Peripheral arterial disease, Indirect revascularisation, Intramuscular injection, Ankle-brachial index, Transcutaneous oxygen tension, Stromal vascular fraction (SVF), Adipose-derived regenerative cells (ADRC), Adipose tissue, Stem cells

Eligibility Criteria

50 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients with critical lower limb ischemia, with resting pain wich can't be adequately managed by opioid analgetics and/or foot ulcers or necrosis, with II-4, III-5 и IV-6 stages of chronic arterial failure according to Rutherford's classification
Ankle-brachial index less than 0.4 and/or ТСрО2 less than 30 mm Hg
Patients with lower limbs' arteries lesions revealed by angiography uneffectiveness or impossibility of limb's revascularisation or patient's refusal of the procedure
Patient is familiar with Participant information sheet
Patient signed informed consent form

Non-inclusion Criteria:

Contraindications for local anesthesia or history of allergy for local anesthetics
Systemic glucocorticoid and/or immunosuppressant therapy
Any condition that might limit compliance (dementia, mental disorders, narcotic drug or alcohol abuse etc.)
Participation in other clinical trials (or administration of investigational drugs) during 3 months prior inclusion
Patients with malignant tumors including postoperative period, patients receiving chemotherapy and/or radiotherapy
Clinically significant abnormalities in results of laboratory tests
Patient received anticoagulants at least 12 hours prior the liposuction
Medical history of heterotopic ossifications
Patients prescribed for glycoprotein inhibitors treatment

Exclusion Criteria:

Patient's refusal from the further participation in trial
Chronic kidney disease IV- V stages (creatinine clearance < 30 mL/min estimated by Cockcroft-Gault formula)
Confirmed syphilis, HIV, hepatitis B or C infections

Dropout Criteria:

Indications for the amputation of the limb

Sites / Locations

Federal State Budgetary Institution "Central Clinical Hospital with Outpatient Health Center" of the Business Administration for the President of the Russian Federation

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ADRC injection

Arm Description

Subjects will undergo liposuction under local anesthesia. Lipoaspirate will be processed to isolate and concentrate Adipose-derived regenerative cells (ADRC). After isolation 10 mL of autologous ADRC suspension will be injected intramuscularly, close to the site of muscle injury. 10 to 20 injections will be performed so as to infiltrate the injured muscle

Outcomes

Primary Outcome Measures

Serious adverse events

Frequency, type and severity of serious adverse events (SAE)

Serious adverse reactions

Frequency, type and severity of serious adverse reactions (SAR)

Secondary Outcome Measures

Changes of ankle-brachial index

Influence of intervention on ankle-brachial index.

Changes of hemodynamics in lower extremity - 1

Influence of intervention on blood flow velocity assessed by arterial duplex scanning.

Changes of hemodynamics in lower extremity - 2

Influence of intervention on pulsatility index assessed by arterial duplex scanning.

Changes of hemodynamics in lower extremity - 3

Influence of intervention on resistance index assessed by arterial duplex scanning.

Metabolic state of targeted tissues measurements

Changes of transcutaneous oxygen tension (ТсРО2) in injured limb assessed by transcutaneous oximetry.

Quality of life monitoring - 1

Quality of life estimated by validated questionnaire: the Short Form (SF-36).

Quality of life monitoring - 2

Quality of life estimated by validated questionnaire:Peripheral Artery Questionnaire.

Full Information

NCT ID

NCT02864654

First Posted

August 5, 2016

Last Updated

August 11, 2016

Sponsor

Central Clinical Hospital w/Outpatient Health Center of Business Administration for the President of Russian Federation

1. Study Identification

Unique Protocol Identification Number

NCT02864654

Brief Title

Effectiveness and Safety of Adipose-Derived Regenerative Cells for the Treatment of Critical Lower Limb Ischemia

Official Title

Effectiveness and Safety of Adipose-Derived Regenerative Cells for the Treatment of Critical Lower Limb Ischemia

Study Type

Interventional

2. Study Status

Record Verification Date

August 2016

Overall Recruitment Status

Unknown status

Study Start Date

July 2016 (undefined)

Primary Completion Date

August 2017 (Anticipated)

Study Completion Date

July 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Central Clinical Hospital w/Outpatient Health Center of Business Administration for the President of Russian Federation

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

Adipose-derived regenerative cells (ADRC) will be extracted from lipoaspirate by enzymatic digestion. 10 mL of autologous ADRC suspension injected intramuscularly, close to the site of muscle injury. All patients will receive cell therapy. This is a single arm study with no control.

Detailed Description

Fat tissue obtainment: Subjects will undergo liposuction under local anesthesia. In this procedure, Ringer's solution with the anesthetic lidocaine and vasoconstrictor adrenaline infused into the adipose compartment to minimize blood loss and contamination of the tissue by peripheral blood cells. 15 minutes later a hollow blunt-tipped 3 mm cannula introduced into the subcutaneous space through small (0.5 cm) incision. The cannula attached to syringe and under gentle suction moved through the adipose compartment, mechanically disrupting the fat tissue. Aspirate volume - approximately 150-200 cc. Procedure time - 30 minutes. ADRC isolation: Harvested adipose tissue will be processed according to patent pending technology based on enzymatic digestion, washing and concentration of cell pellet in 10.5 ml of normal saline. Obtained ADRC divided into 2 portions. First portion (0.5 mL) used for counting, viability and sterility assessment. The second portion (10 ml) placed into sterile syringe for injection. Autologous ADRC administration 10 mL of autologous ADRC suspension will be injected intramuscularly, close to the site of muscle injury. 10 to 20 injections (0.5 to 1.0 mL each) will be performed so as to infiltrate the injured muscle.

6. Conditions and Keywords

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

Critical Limb Ischemia, Arteriosclerosis Obliterans, Peripheral Arterial Disease, Thromboangiitis Obliterans, Diabetic Angiopathies

Keywords

Critical lower limb ischemia, Atherosclerosis obliterans, Diabetic angiopathies, Thromboangiitis obliterans, Ischemic ulcers, Peripheral arterial disease, Indirect revascularisation, Intramuscular injection, Ankle-brachial index, Transcutaneous oxygen tension, Stromal vascular fraction (SVF), Adipose-derived regenerative cells (ADRC), Adipose tissue, Stem cells

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

9 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

ADRC injection

Arm Type

Experimental

Arm Description

Intervention Type

Procedure

Intervention Name(s)

ADRC injection

Intervention Description

10 mL of autologous ADRC suspension will be injected intramuscularly

Intervention Type

Other

Intervention Name(s)

ADRC isolation

Intervention Description

ADRC will be isolated according to patent pending technology based on enzymatic digestion, washing and concentration of cell pellet in 10 ml of normal saline.

Intervention Type

Procedure

Intervention Name(s)

Liposuction

Primary Outcome Measure Information:

Title

Serious adverse events

Description

Frequency, type and severity of serious adverse events (SAE)

Time Frame

4 weeks after injection of ADRC suspension

Title

Serious adverse reactions

Description

Frequency, type and severity of serious adverse reactions (SAR)

Time Frame

4 weeks after injection of ADRC suspension

Secondary Outcome Measure Information:

Title

Changes of ankle-brachial index

Description

Influence of intervention on ankle-brachial index.

Time Frame