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

Peripheral Arterial Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT02864654
• Other study ID #: RU-CCH-07-01-16
• Status: Enrolling by invitation
• Phase: Phase 1/Phase 2
• First received: August 5, 2016
• Last updated: August 11, 2016
• Start date: July 2016
• Est. completion date: July 2018

Study information

• Verified date: August 2016
• Source: Central Clinical Hospital with Outpatient Health Center of Business Administration for the President of Russian Federati
• Contact: n/a
• Is FDA regulated: No
• Health authority: Russia: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 9
• Est. completion date: July 2018
• Est. primary completion date: August 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years to 85 Years

Eligibility

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 ? IV-6 stages of chronic arterial failure according to Rutherford's classification

• Ankle-brachial index less than 0.4 and/or ????2 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

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arteriosclerosis
• Arteriosclerosis Obliterans
• Critical Limb Ischemia
• Diabetic Angiopathies
• Ischemia
• Peripheral Arterial Disease
• Peripheral Vascular Diseases
• Thromboangiitis Obliterans

Intervention

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.

Procedure:
• Liposuction

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Central Clinical Hospital with Outpatient Health Center of Business Administration for the President of Russian Federati

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Serious adverse events	Frequency, type and severity of serious adverse events (SAE)	4 weeks after injection of ADRC suspension	Yes
Primary	Serious adverse reactions	Frequency, type and severity of serious adverse reactions (SAR)	4 weeks after injection of ADRC suspension	Yes
Secondary	Changes of ankle-brachial index	Influence of intervention on ankle-brachial index.	Follow up to completion (24 weeks after intervention)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	Metabolic state of targeted tissues measurements	Changes of transcutaneous oxygen tension (????2) in injured limb assessed by transcutaneous oximetry.	Follow up to completion (24 weeks after intervention)	No
Secondary	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)	No
Secondary	Quality of life monitoring - 2	Quality of life estimated by validated questionnaire:Peripheral Artery Questionnaire.	Follow up to completion (24 weeks after intervention)	No