Clinical trial NCT02869061: Effectiveness and Safety of Adipose-derived Regenerative Cells for Reduction of Risk of Bladder Neck Contracture
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Bladder Neck Obstruction
Bladder Outlet Obstruction
Benign Prostatic Hyperplasia
Urinary Bladder Neck Obstruction
Keywords: Bladder neck obstruction
Bladder outlet obstruction
Benign prostatic hyperplasia
Urinary bladder neck obstruction
Bladder neck contracture
Bladder neck stricture
Bladder neck stenosis
Transurethral resection of the prostate
Prostatectomy
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
Collaborators: name: I.M. Sechenov First Moscow State Medical University
First posted: 2016-08-16
Enrollment: 12
Sex: MALE
Minimum age (years): 40
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Serious adverse events
timeFrame: 4 weeks after injection of ADRC suspension
measure: Serious adverse reactions
timeFrame: Time Frame: 4 weeks after injection of ADRC suspension
Secondary outcomes:
measure: Changes of the volume of residual urine
timeFrame: Follow up to completion (48 weeks after intervention)
measure: Urodynamic changes - 1
timeFrame: Follow up to completion (48 weeks after intervention)
measure: Urodynamic changes - 2
timeFrame: Follow up to completion (48 weeks after intervention)
measure: Urodynamic changes - 3
timeFrame: Follow up to completion (48 weeks after intervention)
measure: Urodynamic changes - 4
timeFrame: Follow up to completion (48 weeks after intervention)
measure: Quality of life monitoring - 1
timeFrame: Follow up to completion (48 weeks after intervention)
measure: Quality of life monitoring - 2
timeFrame: Follow up to completion (48 weeks after intervention)
measure: Bladder neck restenosis control
timeFrame: Follow up to completion (48 weeks after intervention)
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: I.M. Sechenov First Moscow State Medical University
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: I.M. Sechenov First Moscow State Medical University
name: Denis V Butnaru, 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: I.M. Sechenov First Moscow State Medical University
name: Andrey Z Vinarov, MD, PhD, Prof
role: PRINCIPAL_INVESTIGATOR
References: