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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Bladder Neck Obstruction, Bladder Outlet Obstruction, Benign Prostatic Hyperplasia, Urinary Bladder Neck Obstruction

Intervention / Treatment
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* Procedure: Liposuction
* Procedure: Transurethral bladder neck resection.
* Biological: ADRC
* Other: ADRC isolation


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ADRC injection<br>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<br> <br> Procedure: Transurethral bladder neck resection.<br> <br> Biological: ADRC<br>* Injection of ADRC suspension will be performed endoscopically into the bladder neck close to the site of resection.<br>* Other names: Adipose-derived regenerative cells;Other: ADRC isolation<br>* 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.<br>|

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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