Effectiveness and Safety of Adipose-Derived Regenerative Cells for Treatment of Erectile Dysfunction

Effectiveness and Safety of Intracavernosal Administration of Autologous Adipose-Derived Regenerative Cells for Treatment of Erectile Dysfunction

Autologous adipose-derived regenerative cells (ADRC) extracted using Celution 800/CRS System (Cytori Therapeutics Inc) from a portion of the fat harvested from the patient's front abdominal wall. ADRC will be administered one-time intracavernosally. This is a single arm study with no control. All patients receive cell therapy.

Study Overview

• Status: Completed
• Conditions: Erectile Dysfunction; Impotence, Vasculogenic
• Intervention / Treatment: Other: Intracavernosal administration of autologous ADRC; Procedure: Liposuction; Device: 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:

Aspirated fat tissue placed into sterile vessel which inserted into Celution 800/CRS System (Cytori Therapeutics Inc) - closed system for automated and standardized extraction and concentration of ADRC. Celution 800/CRS System drains excess of fluid from fat tissue and estimate it's volume After that lipoaspirate washed extensively with equal volumes of Ringer's solution to remove blood. At the end of this process System indicates required volume of enzyme reagent (Celase®) which should be added immediately by operator. After enzyme treatment Celution 800/CRS System automatically transfers isolated ADRC into washing compartment where ADRC washed and concentrated in 5 mL suspension. Tissue processing time - approximately 60 minutes. ADRC suspension match all requirements listed in technical documentation for Celution 800/CRS System. Obtained ADRC divided into 2 portions. First portion (0.2-0.5 mL) used for counting, viability and sterility assessment. Second portion placed into sterile insulin syringes with needle size 30 G for injection.

Intracavernosal injection of ADRC:

Tourniquet applied immediately prior to injection at the base of the penis. Penis and surrounding skin treated with antiseptic solution. The injection performed on lateral surface of penis bilaterally proximally into the middle and distal parts of corpus cavernosum. Needle is inserted into the corpus cavernosum at the depth of 5-7 mm. Up to 1.0 ml of ADRC suspension injected per single injection. Equal portions of ADRC suspension injected into both corpora cavernosa. Tourniquet removed 20 minutes after ADRC injection.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 119991
    • I.M. Sechenov First Moscow State Medical University
  • 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; Center for Biomedical Technologies

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Patient suffers from erectile dysfunction
• IIEF-5 score less than 21
• Endothelial dysfunction confirmed by EndoPAT measurements
• Patient is familiar with Participant information sheet
• Patient signed informed consent form

Non-inclusion Criteria:

• Contraindications to the local anesthesia or medical history of allergic reactions to local anesthetics
• Patient prescribed for systemic corticosteroids, immunosuppressive drugs, nonsteroidal antiinflammatory drugs, phosphodiesterase-5 inhibitors
• Medical history of penile prosthesis implantation
• Peyronie's disease
• Subcompensated or decompensated forms of chronic diseases of internal organs
• Clinically significant abnormalities in results of laboratory tests
• Any conditions limiting compliance (dementia, neuropsychiatric disease, drug and 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.
• Patient's activated partial thromboplastin time exceeds normal levels more than 1,8 times
• Patients prescribed for anticoagulants treatment or patient received anticoagulants at least one hour prior liposuction
• Medical history of heterotopic ossifications
• Patients prescribed for glycoprotein inhibitors treatment
• Patients with infections or septic condition

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
• Patients with hypogonadism

Dropout Criteria:

• Direct indications on immediate initiation of treatment with drugs that have proven effect on erectile function

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: ADRC injection

Other: Intracavernosal administration of autologous ADRC; Subjects will undergo liposuction under local anesthesia. Lipoaspirate will be processed to isolate and concentrate adipose-derived regenerative cells (ADRC). After isolation autologous ADRC suspension will be injected intracavernosally.; Procedure: Liposuction; Device: ADRC isolation; ADRC isolation performed using Celution 800/CRS System (Cytori Therapeutics Inc) according to manufacturer's protocol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SAEs monitoring	Types, probability and severity of treatment emergent serious adverse events (SAEs)	2 weeks after treatment
SARs monitoring	Types, probability and severity of treatment emergent serious adverse reactions (SARs)	2 weeks after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of life monitoring	Quality of life estimated by validated questionnaires: the Short Form (36) Health Survey (SF-36), International Index of Erectile Function (IIEF-5), Sexual Encounter Profile (SEP), Erection Hardness Score (EHS), Global Assessment Question (GAQ)	Follow up to completion (up to 24 weeks after treatment)
Penile colour Doppler ultrasonography combined with prostaglandin-E1 injection	Colour penile Doppler ultrasonography with intracavernosal injection of prostaglandin-E1 10 ug. Arterial diameter, peak systolic flow velocity, end diastolic flow velocity and resistance index measured before and 15 min after prostaglandin-E1 10ug intracavernosal injection.	Follow up to completion (up to 24 weeks after treatment)
Endothelial function assessment	Endothelial function assessed by EndoPAT or similar device measurements.	Follow up to completion (up to 24 weeks after treatment)
Arterial stiffness assessment	Arterial stiffness assessed by EndoPAT or similar device measurements.	Follow up to completion (up to 24 weeks after treatment)

Collaborators and Investigators

• Sponsor: Central Clinical Hospital w/Outpatient Health Center of Business Administration for the President of Russian Federation
• Collaborators: I.M. Sechenov First Moscow State Medical University
• Investigators: Principal Investigator: Mikhail E Chalyy, MD, PhD, Prof, I.M. Sechenov First Moscow State Medical University

Study record dates

Study Major Dates

• Study Start: April 1, 2015
• Primary Completion (Actual): November 1, 2016
• Study Completion (Actual): November 1, 2016

Study Registration Dates

• First Submitted: June 9, 2015
• First Submitted That Met QC Criteria: June 11, 2015
• First Posted (Estimate): June 15, 2015

Study Record Updates

• Last Update Posted (Estimate): November 30, 2016
• Last Update Submitted That Met QC Criteria: November 29, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Erectile Dysfunction; Stem Cells; ADRC; Male Impotence; Male Sexual Impotence; Adipose-Derived Regenerative Cells; Fat Tissue; Arteriogenic Impotence; Venogenic Impotence; Vasculogenic Impotence
• Additional Relevant MeSH Terms: Mental Disorders; Sexual Dysfunctions, Psychological; Sexual Dysfunction, Physiological; Erectile Dysfunction; Impotence, Vasculogenic
• Other Study ID Numbers: RU-CCH-01-01-15