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

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.

Study Overview

• Status: Unknown
• Conditions: Diabetic Angiopathies; Peripheral Arterial Disease; Critical Limb Ischemia; Thromboangiitis Obliterans; Arteriosclerosis Obliterans
• Intervention / Treatment: Procedure: Liposuction; Procedure: ADRC injection; Other: ADRC isolation

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.

• Study Type: Interventional
• Enrollment (Anticipated): 9
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 121359
    • Federal State Budgetary Institution "Central Clinical Hospital with Outpatient Health Center" of the Business Administration for the President of the Russian Federation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: ADRC injection; 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	Procedure: Liposuction; Procedure: ADRC injection; 10 mL of autologous ADRC suspension will be injected intramuscularly; Other: ADRC isolation; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serious adverse events	Frequency, type and severity of serious adverse events (SAE)	4 weeks after injection of ADRC suspension
Serious adverse reactions	Frequency, type and severity of serious adverse reactions (SAR)	4 weeks after injection of ADRC suspension

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of ankle-brachial index	Influence of intervention on ankle-brachial index.	Follow up to completion (24 weeks after intervention)
Changes of hemodynamics in lower extremity - 1	Influence of intervention on blood flow velocity assessed by arterial duplex scanning.	Follow up to completion (24 weeks after intervention)
Changes of hemodynamics in lower extremity - 2	Influence of intervention on pulsatility index assessed by arterial duplex scanning.	Follow up to completion (24 weeks after intervention)
Changes of hemodynamics in lower extremity - 3	Influence of intervention on resistance index assessed by arterial duplex scanning.	Follow up to completion (24 weeks after intervention)
Metabolic state of targeted tissues measurements	Changes of transcutaneous oxygen tension (ТсРО2) in injured limb assessed by transcutaneous oximetry.	Follow up to completion (24 weeks after intervention)
Quality of life monitoring - 1	Quality of life estimated by validated questionnaire: the Short Form (SF-36).	Follow up to completion (24 weeks after intervention)
Quality of life monitoring - 2	Quality of life estimated by validated questionnaire:Peripheral Artery Questionnaire.	Follow up to completion (24 weeks after intervention)

Collaborators and Investigators

• Sponsor: Central Clinical Hospital w/Outpatient Health Center of Business Administration for the President of Russian Federation
• Investigators: Principal Investigator: Andrey A Kalinin, MD, PhD, Federal State Budgetary Institution "Central Clinical Hospital with Outpatient Health Center" of the Business Administration for the President of the Russian Federation; Study Director: Evgeny R Lysenko, MD, PhD, Prof, FSBI Federal Clinial Center of Advanced medical Technologies FMBA of Russia

Study record dates

Study Major Dates

• Study Start: July 1, 2016
• Primary Completion (ANTICIPATED): August 1, 2017
• Study Completion (ANTICIPATED): July 1, 2018

Study Registration Dates

• First Submitted: August 5, 2016
• First Submitted That Met QC Criteria: August 11, 2016
• First Posted (ESTIMATE): August 12, 2016

Study Record Updates

• Last Update Posted (ESTIMATE): August 12, 2016
• Last Update Submitted That Met QC Criteria: August 11, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: Stem cells; Peripheral arterial disease; Adipose tissue; Diabetic angiopathies; Ankle-brachial index; Intramuscular injection; Critical lower limb ischemia; Adipose-derived regenerative cells (ADRC); Stromal vascular fraction (SVF); Atherosclerosis obliterans; Thromboangiitis obliterans; Ischemic ulcers; Indirect revascularisation; Transcutaneous oxygen tension
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Arterial Occlusive Diseases; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Atherosclerosis; Vasculitis; Ischemia; Peripheral Arterial Disease; Peripheral Vascular Diseases; Arteriosclerosis; Diabetic Angiopathies; Thromboangiitis Obliterans; Arteriosclerosis Obliterans
• Other Study ID Numbers: RU-CCH-07-01-16

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED