Effectiveness and Safety of Adipose-derived Regenerative Cells for Reduction of Risk of Bladder Neck Contracture

Effectiveness and Safety of Local Endoscopically-assisted Administration of Autologous Adipose-derived Regenerative Cells for Reduction of Risk of Postoperative Bladder Neck Contracture in Male Patients

Autologous adipose-derived regenerative cells (ADRC) will be extracted from lipoaspirate by enzymatic digestion from a portion of the fat harvested from the patient's front abdominal wall. Transurethral bladder neck resection followed by the injection of ADRCs suspension will be performed. This is a single arm study with no control. All patients receive cell therapy.

Study Overview

• Status: Unknown
• Conditions: Benign Prostatic Hyperplasia; Bladder Outlet Obstruction; Urinary Bladder Neck Obstruction; Bladder Neck Obstruction
• Intervention / Treatment: Procedure: Liposuction; Procedure: Transurethral bladder neck resection.; Biological: ADRC; 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 9.5 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 (9 ml) placed into sterile syringe for injection.

Surgery:

Transurethral endoscopic loop resection of bladder neck will be performed.

Autologous ADRC administration:

Injection of ADRC suspension will be performed immediately after bladder neck resection. 9 to 18 injections (0.5 to 1.0 mL each) will be injected with endoscopic needle into the bladder neck close to the site of resection. All injections will be performed during single procedure.

• Study Type: Interventional
• Enrollment (Anticipated): 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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Bladder neck contracture after transurethral prostate resection.
• Obstructive pattern of urine flow rate with maximum flow rate below 15 mL/s
• Patient is familiar with Participant information sheet
• Patient signed informed consent form

Non-inclusion Criteria:

• Contraindications for spinal, epidural or inhalation anesthesia
• Urethral strictures
• Genitourinary inflammatory diseases
• Prostate-specific antigen (PSA) level above 4 ng/mL
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• 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; Subjects will be undergone liposuction under local anesthesia. Adipose-derived regenerative cells (ADRC) will be isolated from lipoaspirate by enzymatic digestion. Transurethral bladder neck resection followed by the injection of ADRC suspension will be performed. This is a single arm study with no control. All patients receive cell therapy.

Procedure: Liposuction; Procedure: Transurethral bladder neck resection.; Biological: ADRC; Injection of ADRC suspension will be performed endoscopically into the bladder neck close to the site of resection.; Other Names: Adipose-derived regenerative cells; Other: ADRC isolation; ADRC will be isolated according to patent pending technology based on enzymatic digestion, washing and concentration of cell pellet in up to 9.5 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)	Time Frame: 4 weeks after injection of ADRC suspension

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of the volume of residual urine	Influence of the procedure on the volume of residual urine assessed by ultrasonography	Follow up to completion (48 weeks after intervention)
Urodynamic changes - 1	Influence of the intervention on urinary flow rate: maximum flow rate	Follow up to completion (48 weeks after intervention)
Urodynamic changes - 2	Influence of the intervention on urinary flow rate: average flow rate	Follow up to completion (48 weeks after intervention)
Urodynamic changes - 3	Influence of the intervention on urinary flow rate: total volume voided	Follow up to completion (48 weeks after intervention)
Urodynamic changes - 4	Influence of the intervention on urinary flow rate: maximum flow time	Follow up to completion (48 weeks after intervention)
Quality of life monitoring - 1	Quality of life estimated by validated questionnaire: the Short Form (SF-36).	Follow up to completion (48 weeks after intervention)
Quality of life monitoring - 2	Quality of life estimated by validated questionnaire: International Prostatic Symptom Score (IPSS).	Follow up to completion (48 weeks after intervention)
Bladder neck restenosis control	Revision of bladder neck structure by retrograde urethrography	Follow up to completion (48 weeks after intervention)

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: Denis V Butnaru, MD, PhD, I.M. Sechenov First Moscow State Medical University; Principal Investigator: Andrey Z Vinarov, MD, PhD, Prof, I.M. Sechenov First Moscow State Medical University

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Anticipated): December 1, 2017
• Study Completion (Anticipated): December 1, 2018

Study Registration Dates

• First Submitted: August 8, 2016
• First Submitted That Met QC Criteria: August 11, 2016
• First Posted (Estimate): August 16, 2016

Study Record Updates

• Last Update Posted (Estimate): August 16, 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; Adipose tissue; Prostatectomy; Benign prostatic hyperplasia; Bladder outlet obstruction; Transurethral resection of the prostate; Adipose-derived regenerative cells (ADRC); Bladder neck obstruction; Urinary bladder neck obstruction; Bladder neck contracture; Bladder neck stricture; Bladder neck stenosis; Stromal vascular fraction (SVF)
• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Urinary Bladder Diseases; Neurologic Manifestations; Prostatic Diseases; Joint Diseases; Musculoskeletal Diseases; Muscular Diseases; Dyskinesias; Urethral Diseases; Dystonia; Urethral Obstruction; Prostatic Hyperplasia; Hyperplasia; Torticollis; Urinary Bladder Neck Obstruction; Contracture
• Other Study ID Numbers: RU-CCH-01-02-15

Plan for Individual participant data (IPD)

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