Use of Autologous Adipose-Derived Stem/Stromal Cells (AD-cSVF) in Symptomatic Benign Prostate Hypertrophy

NCT02961114 | Withdrawn Phase 1 DMC

• 1 other identifier: RGV GARM 4
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

Benign prostate hypertrophy (BPH) and inflammation are common non-cancerous enlargement of the prostate, which result in urinary interference and incomplete drainage of the bladder. Compression of the urethra is common cause of such resistance of full draining, and may over time result in progressive hypertrophy, instability, urgency, nocturia and weakness of the bladder musculature. Prostatic growth frequently begins in the 30s, and it is estimated that 50% of all males have benign enlargement leading to 75% by age 80. BPH and low grade inflammation is one of the ten most prominent and costly disorders in males over 50. Urinary tract symptoms are divided into issues of storage, voiding, and post-void symptoms can be associated with bladder outlet obstruction (BOO). This study utilizes isolation of adipose-derived stem/stromal cellular stromal vascular fraction (AD-cSVF) deployed as an IV suspension in sterile Normal Saline (500cc). Due to the anti-inflammatory and immunomodulatory effects common to AD-cSVF are tested in relief of the inflammatory elements and the concurrent hypertrophy in BPH. Early pilot use has suggested a positive effect on these issues, and have relieved much of the incomplete voiding, pain, nocturia, delay in starting/stopping urination, and increased urgency and frequency. Lipoharvesting of Adipose-Derived tissue stromal vascular fraction (AD-tSVF) is now a common closed access to subdermal adipose stromal/stem cell population consisting of both stem and stromal cells, each of which are felt to contribute a wide variety of effects and potentials. Closed, sterile isolation of the AD-cSVF is possible with advent of closed systems to enzymatically release these cells from the actual matrix (scaffolding) within the adipose tissue complex (ATC). This group of largely un-designated cell population is isolated and concentrated via a standard gradient layer separation by centrifugation. This cellular isolate is then suspended in an IV of 500 cc Normal Saline and reintroduced to the patient. This study is examining the clinical safety and efficacy of this approach, as well as tracking the duration of effects and establish a therapeutic interval.

Conditions

BPH; Nocturia; BPH With Urinary Obstruction; Prostatism; Prostate Inflammation

Keywords

Prostatitis, Chronic; Nocturia; BPH With Urinary Obstruction

Outcome Measures

Primary Outcomes (2)

• Adverse Events

  Report of minor and severe adverse effects caused by the procedures

  Outcome measured at 1 month

• Clinical Symptom Changes

  Assessment of change from baseline (0) of frequency, urgency, pain, voiding time, and flow rate during voiding

  Baseline, 1 Month, 6 Months, 1 years

Secondary Outcomes (3)

• Pain on Voiding

  Baseline, 6 month, 1 year

• Change of BPH Symptom Score

  Baseline, 6 month, 12 month

• Change in BPH Symptom Score

  Baseline, 6 month, 1 year

Study Arms (3)

Microcannula Harvest Adipose

EXPERIMENTAL

Acquisition of AD-tSVF via closed syringe microcannula harvest from subdermal fat deposits

Procedure: Microcannula Harvest Adipose

Centricyte 1000

EXPERIMENTAL

Autologous AD-tSVF via enzymatic isolation/concentration via Centricyte 1000 closed system to create AD-cSVF

Device: Centricyte 1000

IV Sterile Normal Saline

EXPERIMENTAL

Re-suspension of AD-cSVF pellet in Normal Saline for deployment via IV

Biological: IV Sterile Normal Saline

Interventions

Microcannula Harvest Adipose PROCEDURE

Use of closed syringe microcannula harvest of autologous AD-tSVF from subdermal adipose deposits to create a AD-cSVF

Microcannula Harvest Adipose

Centricyte 1000 DEVICE

Use of Centricyte 1000 closed system digestion, incubation/agitation, and centrifugation to acquire a concentrated pellet of AD-cSVF

Centricyte 1000

IV Sterile Normal Saline BIOLOGICAL

Sterile Normal Saline deployment of AD-cSVF in suspension of 500cc in IV pathway

IV Sterile Normal Saline

Eligibility Criteria

• Age: 30 Years - 80 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented history BPH for at least 1 year
• AUA SI greater than or equal to score of 15
• Qmax \< 15 ml/sec
• Severe nocturia
• Prostate Specific Antigen (PSA) \> 4 ng/mL with documentation of non-malignancy

You may not qualify if:

• History of illness or conditions that may interfere with study or endanger subject
• Use of prescription medication that may interfere with study or endanger subject within 30 days
• History of surgical procedures for BPH or documented prostate cancer
• Post-void residual urine volumes of \> 350 cc
• PSA \> 10 ng/mL
• Prostate cancer not ruled out by biopsy if PSA is consistently higher than 4 ng/mL

Sponsors & Collaborators

• Robert W. Alexander, MD, FICS: lead
• Terry, Glenn C., M.D.: collaborator

Study Sites (2)

Global Alliance for Regenerative Medicine-USA

Stevensville, Montana, 59870, United States

Location

Regenevita LLC

Stevensville, Montana, 59870, United States

Location

Related Publications (20)

• Chang RT, Kirby R, Challacombe BJ. Is there a link between BPH and prostate cancer? Practitioner. 2012 Apr;256(1750):13-6, 2.

  PMID: 22792684 BACKGROUND

• Guess HA, Arrighi HM, Metter EJ, Fozard JL. Cumulative prevalence of prostatism matches the autopsy prevalence of benign prostatic hyperplasia. Prostate. 1990;17(3):241-6. doi: 10.1002/pros.2990170308.

  PMID: 1700403 BACKGROUND

• Fenter TC, Naslund MJ, Shah MB, Eaddy MT, Black L. The cost of treating the 10 most prevalent diseases in men 50 years of age or older. Am J Manag Care. 2006 Mar;12(4 Suppl):S90-8.

  PMID: 16551207 BACKGROUND

• White JM JR, O'Brien DP III. Incontinence and Stream Abnormalities. In: Walker HK, Hall WD, Hurst JW, editors. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition. Boston: Butterworths; 1990. Chapter 185. Available from http://www.ncbi.nlm.nih.gov/books/NBK295/

  PMID: 21250138 BACKGROUND

• Sarma AV, Wei JT. Clinical practice. Benign prostatic hyperplasia and lower urinary tract symptoms. N Engl J Med. 2012 Jul 19;367(3):248-57. doi: 10.1056/NEJMcp1106637. No abstract available.

  PMID: 22808960 BACKGROUND

• Bartsch G, Rittmaster RS, Klocker H. Dihydrotestosterone and the concept of 5alpha-reductase inhibition in human benign prostatic hyperplasia. World J Urol. 2002 Apr;19(6):413-25. doi: 10.1007/s00345-002-0248-5.

  PMID: 12022710 BACKGROUND

• Lagiou P, Mantzoros CS, Tzonou A, Signorello LB, Lipworth L, Trichopoulos D. Serum steroids in relation to benign prostatic hyperplasia. Oncology. 1997 Nov-Dec;54(6):497-501. doi: 10.1159/000227609.

  PMID: 9394847 BACKGROUND

• Roberts RO, Jacobson DJ, Rhodes T, Klee GG, Leiber MM, Jacobsen SJ. Serum sex hormones and measures of benign prostatic hyperplasia. Prostate. 2004 Oct 1;61(2):124-31. doi: 10.1002/pros.20080.

  PMID: 15305335 BACKGROUND

• Ho CK, Nanda J, Chapman KE, Habib FK. Oestrogen and benign prostatic hyperplasia: effects on stromal cell proliferation and local formation from androgen. J Endocrinol. 2008 Jun;197(3):483-91. doi: 10.1677/JOE-07-0470.

  PMID: 18492814 BACKGROUND

• Niu YJ, Ma TX, Zhang J, Xu Y, Han RF, Sun G. Androgen and prostatic stroma. Asian J Androl. 2003 Mar;5(1):19-26.

  PMID: 12646998 BACKGROUND

• Chyou PH, Nomura AM, Stemmermann GN, Hankin JH. A prospective study of alcohol, diet, and other lifestyle factors in relation to obstructive uropathy. Prostate. 1993;22(3):253-64. doi: 10.1002/pros.2990220308.

  PMID: 7683816 BACKGROUND

• Wasserman NF. Benign prostatic hyperplasia: a review and ultrasound classification. Radiol Clin North Am. 2006 Sep;44(5):689-710, viii. doi: 10.1016/j.rcl.2006.07.005.

  PMID: 17030221 BACKGROUND

• Parsons JK. Benign Prostatic Hyperplasia and Male Lower Urinary Tract Symptoms: Epidemiology and Risk Factors. Curr Bladder Dysfunct Rep. 2010 Dec;5(4):212-218. doi: 10.1007/s11884-010-0067-2. Epub 2010 Sep 7.

  PMID: 21475707 BACKGROUND

• Silva J, Silva CM, Cruz F. Current medical treatment of lower urinary tract symptoms/BPH: do we have a standard? Curr Opin Urol. 2014 Jan;24(1):21-8. doi: 10.1097/MOU.0000000000000007.

  PMID: 24231531 BACKGROUND

• Roehrborn CG, Boyle P, Nickel JC, Hoefner K, Andriole G; ARIA3001 ARIA3002 and ARIA3003 Study Investigators. Efficacy and safety of a dual inhibitor of 5-alpha-reductase types 1 and 2 (dutasteride) in men with benign prostatic hyperplasia. Urology. 2002 Sep;60(3):434-41. doi: 10.1016/s0090-4295(02)01905-2.

  PMID: 12350480 BACKGROUND

• Roehrborn CG, Bruskewitz R, Nickel JC, McConnell JD, Saltzman B, Gittelman MC, Malek GH, Gottesman JE, Suryawanshi S, Drisko J, Meehan A, Waldstreicher J; Proscar Long-Term Efficacy and Safety Study Group. Sustained decrease in incidence of acute urinary retention and surgery with finasteride for 6 years in men with benign prostatic hyperplasia. J Urol. 2004 Mar;171(3):1194-8. doi: 10.1097/01.ju.0000112918.74410.94.

  PMID: 14767299 BACKGROUND

• Greco KA, McVary KT. The role of combination medical therapy in benign prostatic hyperplasia. Int J Impot Res. 2008 Dec;20 Suppl 3:S33-43. doi: 10.1038/ijir.2008.51.

  PMID: 19002123 BACKGROUND

• Prieto J, Murphy CL, Moore KN, Fader M. Intermittent catheterisation for long-term bladder management. Cochrane Database Syst Rev. 2014 Sep 10;(9):CD006008. doi: 10.1002/14651858.CD006008.pub3.

  PMID: 25208303 BACKGROUND

• Bent S, Kane C, Shinohara K, Neuhaus J, Hudes ES, Goldberg H, Avins AL. Saw palmetto for benign prostatic hyperplasia. N Engl J Med. 2006 Feb 9;354(6):557-66. doi: 10.1056/NEJMoa053085.

  PMID: 16467543 BACKGROUND

• Ma CH, Lin WL, Lui SL, Cai XY, Wong VT, Ziea E, Zhang ZJ. Efficacy and safety of Chinese herbal medicine for benign prostatic hyperplasia: systematic review of randomized controlled trials. Asian J Androl. 2013 Jul;15(4):471-82. doi: 10.1038/aja.2012.173. Epub 2013 Jun 3.

  PMID: 23728585 BACKGROUND

MeSH Terms

Conditions

Nocturia; Prostatism; Prostatitis; Bronchiolitis Obliterans Syndrome

Condition Hierarchy (Ancestors)

Lower Urinary Tract Symptoms; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Prostatic Diseases; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Male Urogenital Diseases; Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator, Science

Study Record Dates

• First Submitted: November 8, 2016
• First Posted: November 10, 2016
• Study Start: November 1, 2019
• Primary Completion: December 1, 2022
• Study Completion: July 1, 2023
• Last Updated: January 12, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will share

Locations

US (2)