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

Nocturia Clinical Trial

— SVF-BPN  

Official title:

Use of Autologous Adipose-Derived Stem/Stromal Cells In Symptomatic Benign Prostate Hypertrophy

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02961114
• Other study ID #: RGV GARM 4
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• Start date: November 1, 2019
• Est. completion date: July 2023

Study information

• Verified date: January 2021
• Source: Healeon Medical Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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. BPH is often a progressive disease and may lead to increased urinary stasis and increased risk of urinary tract infections.

Urinary tract symptoms are divided into issues of storage, voiding, and post-void symptoms can be associated with bladder outlet obstruction (BOO). Storage symptoms include need to urinate frequently, waking at night to urinate (nocturia), and incontinence (involuntary). Voiding issues include urinary hesitancy, intermittency (start/stopping flow), leaking after voiding and may include some pain (dysuria) associated with urination. Post-voiding symptoms include abdominal pain, feeling of full bladder, acute urinary retention and frequency, dysuria, hesitancy, etc.

Causation may be associated with age related changes in androgens (such as testosterone and others), but do not seem to be the direct cause of the enlargement.

Androgens promote prostate cell proliferation, but relatively low levels of testosterone are often found in patients with BPH.

Treatment often has been aimed at lifestyle change (exercise, decrease nighttime fluid intake, moderating alcohol and caffeine, decrease certain anticholinergic medications. Use of medication have some advantages, including alpha blocker and 5 alpha-reductase inhibitors, and some broad spectrum antibiotics (like Ciprofloxacin) seem to help many of those with increasing symptoms. Self catheterization and surgery are occasionally needed for patient comfort and reduction of symptomatology.

Alternative remedies include herbal remedies (saw palmetto) and anecdotal effects in patients receiving parenteral stem/stromal cell therapies for other clinical issues. Initially commented that the patient reported improvement of symptoms, have led to this study to determine if any long-interval therapy may be as effective as surgery or catheterization.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: July 2023
• Est. primary completion date: December 2022
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 30 Years to 80 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• BPH
• BPH With Urinary Obstruction
• Hypertrophy
• Inflammation
• Nocturia
• Prostate Inflammation
• Prostatic Hyperplasia
• Prostatism
• Prostatitis

Intervention

Procedure:
• Microcannula Harvest Adipose
Use of closed syringe microcannula harvest of autologous AD-tSVF from subdermal adipose deposits to create a AD-cSVF

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

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

Locations

Country	Name	City	State
United States	Global Alliance for Regenerative Medicine-USA	Stevensville	Montana
United States	Regenevita LLC	Stevensville	Montana

Sponsors (2)

Lead Sponsor	Collaborator
Robert W. Alexander, MD, FICS	Terry, Glenn C., M.D.

Country where clinical trial is conducted

United States, 

References & Publications (20)

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. Review. — View Citation

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. — View Citation

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

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

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. Epub 2010 Sep 7. — View Citation

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. Review. Update in: Cochrane Database Syst Rev. 2017 Aug 08;8:CD006008. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Review. Erratum in: N Engl J Med. 2012 Aug 16;367(7):681. — View Citation

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. Review. — View Citation

Wasserman NF. Benign prostatic hyperplasia: a review and ultrasound classification. Radiol Clin North Am. 2006 Sep;44(5):689-710, viii. Review. — View Citation

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. — View Citation

* Note: There are 20 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse Events	Report of minor and severe adverse effects caused by the procedures	Outcome measured at 1 month
Primary	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	Pain on Voiding	Visual Analog Pain Scale (VAS) designated as levels pain 1-10	Baseline, 6 month, 1 year
Secondary	Change of BPH Symptom Score	BPH Symptom Score change from baseline use American Urological Association Symptom Score Index change from baseline using Amercian Urological Association Symptom Score Index (AUA SI)	Baseline, 6 month, 12 month
Secondary	Change in BPH Symptom Score	Change from Baseline of Measured International Prostate Symptom Score (I-PPS)	Baseline, 6 month, 1 year