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

Phase 1

• Conditions: Thromboangiitis Obliterans; Diabetic Angiopathies; Peripheral Arterial Disease; Critical Limb Ischemia; Arteriosclerosis Obliterans
• Interventions: Procedure: ADRC injection; Other: ADRC isolation; Procedure: Liposuction

• Registration Number: NCT02864654
• Lead Sponsor: Central Clinical Hospital w/Outpatient Health Center of Business Administration for the President of Russian Federation

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.

Study Timeline

• Study Start: 2016-07
• Status Verified: 2016-08
• Study First Submitted: 2016-08-05
• Study First Submitted QC: 2016-08-11
• Last Update Submitted: 2016-08-11
• Study First Posted: 2016-08-12
• Last Update Posted: 2016-08-12
• Primary Completion: 2017-08
• Study Completion: 2018-07

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 9

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
ADRC injection	Liposuction	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
ADRC injection	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
ADRC injection	ADRC isolation	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

Primary Outcome Measures

Name	Time	Method
Serious adverse reactions	4 weeks after injection of ADRC suspension	Frequency, type and severity of serious adverse reactions (SAR)
Serious adverse events	4 weeks after injection of ADRC suspension	Frequency, type and severity of serious adverse events (SAE)

Secondary Outcome Measures

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

Trial Locations

Locations (1)

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