Clinical trial NCT02864654: 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
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: 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
Lead sponsor: Central Clinical Hospital w/Outpatient Health Center of Business Administration for the President of Russian Federation
Sponsor class: OTHER_GOV
First posted: 2016-08-12
Enrollment: 9
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Serious adverse events
timeFrame: 4 weeks after injection of ADRC suspension
measure: Serious adverse reactions
timeFrame: 4 weeks after injection of ADRC suspension
Secondary outcomes:
measure: Changes of ankle-brachial index
timeFrame: Follow up to completion (24 weeks after intervention)
measure: Changes of hemodynamics in lower extremity - 1
timeFrame: Follow up to completion (24 weeks after intervention)
measure: Changes of hemodynamics in lower extremity - 2
timeFrame: Follow up to completion (24 weeks after intervention)
measure: Changes of hemodynamics in lower extremity - 3
timeFrame: Follow up to completion (24 weeks after intervention)
measure: Metabolic state of targeted tissues measurements
timeFrame: Follow up to completion (24 weeks after intervention)
measure: Quality of life monitoring - 1
timeFrame: Follow up to completion (24 weeks after intervention)
measure: Quality of life monitoring - 2
timeFrame: Follow up to completion (24 weeks after intervention)
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: Federal State Budgetary Institution "Central Clinical Hospital with Outpatient Health Center" of the Business Administration for the President of the Russian Federation
Study officials:
affiliation: Federal State Budgetary Institution "Central Clinical Hospital with Outpatient Health Center" of the Business Administration for the President of the Russian Federation
name: Andrey A Kalinin, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Federal State Budgetary Institution "Central Clinical Hospital with Outpatient Health Center" of the Business Administration for the President of the Russian Federation
name: Andrey A Pulin, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: FSBI Federal Clinial Center of Advanced medical Technologies FMBA of Russia
name: Evgeny R Lysenko, MD, PhD, Prof
role: STUDY_DIRECTOR
References: