Effects of TNF Blockade on Human BPH/LUTS

NCT ID: NCT06062875

Last Updated: 2024-11-21

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-01-24
• Study Completion Date: 2028-06-01

Brief Summary

Specific Aim 1. To evaluate the efficacy of TNF antagonist action in BPH/LUTS Specific Aim 2. Define the consequences of TNF antagonist therapy on prostate tissue Specific Aim 3. Identify genetic predictors to stratify patients with differential response to TNF-antagonist therapy.

Detailed Description

The purpose of this study is to investigate whether an anti-inflammatory drug commonly used for a range of autoimmune diseases may be useful to provide symptomatic relief, prostate shrinkage, and/or decrease prostatic inflammation in patients with benign prostatic hyperplasia (BPH), sometimes described as prostatic enlargement.

BPH includes a significant amount of inflammation. Prior studies show that there are common links between autoimmune diseases, inflammation, and BPH. TNF-antagonists such as adalimumab are anti-inflammatory drugs commonly prescribed to treat autoimmune diseases. NorthShore researchers, including Drs. Glaser, Hayward, and Helfand, showed that these drugs reduced the incidence of BPH in patients with autoimmune diseases.

In this study, the investigators will study the TNF-antagonist adalimumab in patients with BPH who do not have autoimmune diseases. Adalimumab used in this study is investigational because it is not approved by the FDA for BPH. However, adalimumab is an approved, widely-prescribed, and commonly used drug utilized in a variety of conditions including rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, plaque psoriasis, hidradenitis suppurativa, and uveitis. It has a well-studied side effect profile and was approved for use by the FDA in 2008. The purpose of this study is to determine whether adalimumab is an effective way to reduce symptoms and/or prostatic inflammation in BPH patients without autoimmune diseases. If this research is successful it may open up a new method of therapy for patients with BPH and associated symptoms.

This study will include a total of 70 subjects. Of those subjects, all 70 will be from NorthShore University HealthSystem ("NorthShore").

Conditions

Benign Prostatic Hyperplasia (BPH)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

adalimumab

adalimumab 40 mg every 2 weeks

Group Type: ACTIVE_COMPARATOR

Adalimumab

Intervention Type: DRUG

Adalimumab will be delivered subcutaneously (under the skin) at a dose of 40mg every 2 weeks for a total of 6 doses.

Placebo

placebo injection (saline) every 2 weeks.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Adalimumab

Adalimumab will be delivered subcutaneously (under the skin) at a dose of 40mg every 2 weeks for a total of 6 doses.

Intervention Type: DRUG

Other Intervention Names

Placebo will be administered subcutaneously every 2 weeks, for a total of 6 injections.

Eligibility Criteria

Inclusion Criteria

• Male sex
• Age 45-80 years
• Diagnosed by physician with BPH
• Prostate volume ≥ 60mL
• IPSS ≥ 8
• Able and willing to complete questionnaires
• Able and willing to provide informed consent
• Able to read, write, and speak in English
• No prior treatment with TNF inhibitor (adalimumab, etanercept, infliximab, certolizumab, golimumab)
• No plans to move from study area in the next 6 months

Deferral Criteria:

• Microscopic hematuria without appropriate workup per AUA/Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction (SUFU) Guidelines
• Positive urine culture

Exclusion Criteria

• Female sex or intersex
• Age < 45 or > 80 years
• Being a prisoner or detainee
• Urinary retention with need for catheterization
• Gross hematuria
• Contraindication to treatment with adalimumab (e.g., presence of sepsis or active infection, active tuberculosis, Hepatitis B infection, invasive fungal infection, lymphoma, leukemia or other active malignancy, congestive heart failure, significant hematologic abnormality, allergy to adalimumab or its components, anti-drug antibodies, congestive heart failure)
• Diagnosis of autoimmune disease (rheumatoid arthritis, plaque psoriasis, ulcerative colitis, Crohn's disease, hidradenitis suppurativa, spondyloarthritis)
• Interstitial cystitis
• Pelvic or endoscopic genitourinary surgery within the preceding 6 months (not including diagnostic cystoscopy)
• History of lower urinary tract or pelvic malignancy including prostate cancer; history of pelvic radiation therapy
• Ongoing symptomatic urethral stricture
• Current chemotherapy or other cancer therapy
• Severe neurological or psychiatric disorder that would prevent study participation (e.g., bipolar disorder, psychotic disorder, Alzheimer's Disease)
• Current moderate or severe substance use disorder

• Minimum Eligible Age: 45 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

Endeavor Health

OTHER

Sponsor Role: lead

Responsible Party

Alexander Glaser

M.D.; Clinical Assistant Professor University of Chicago Pritzker School of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Simon W Hayward, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Endeavor Health

Alexander P Glaser, M.D.

Role: PRINCIPAL_INVESTIGATOR

Endeavor Health

Locations

NorthShore University HealthSystem

Glenview, Illinois, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Malgorzata Antoniak, Ph.D.

Role: CONTACT

MAntoniak@northshore.org

847-503-4282

Pooja Talaty, MS MHA CCRP

Role: CONTACT

PTalaty@northshore.org

847-503-4280

Facility Contacts

Pooja Talaty, MS MHA CCRP

Role: primary

PTalaty@northshore.org

847-503-4280

Simon W Hayward, Ph.D

Role: backup

Alexander P Glaser, M.D.

Role: backup

References

Vickman RE, Aaron-Brooks L, Zhang R, Lanman NA, Lapin B, Gil V, Greenberg M, Sasaki T, Cresswell GM, Broman MM, Paez JS, Petkewicz J, Talaty P, Helfand BT, Glaser AP, Wang CH, Franco OE, Ratliff TL, Nastiuk KL, Crawford SE, Hayward SW. TNF is a potential therapeutic target to suppress prostatic inflammation and hyperplasia in autoimmune disease. Nat Commun. 2022 Apr 19;13(1):2133. doi: 10.1038/s41467-022-29719-1.

Reference Type: BACKGROUND

PMID: 35440548 (View on PubMed)

Kramer G, Mitteregger D, Marberger M. Is benign prostatic hyperplasia (BPH) an immune inflammatory disease? Eur Urol. 2007 May;51(5):1202-16. doi: 10.1016/j.eururo.2006.12.011. Epub 2006 Dec 11.

Reference Type: BACKGROUND

PMID: 17182170 (View on PubMed)

Glaser AP, Mansfield S, Smith AR, Helfand BT, Lai HH, Sarma A, Yang CC, Taddeo M, Clemens JQ, Cameron AP, Flynn KE, Andreev V, Fraser MO, Erickson BA, Kirkali Z, Griffith JW; LURN Study Group. Impact of Sleep Disturbance, Physical Function, Depression and Anxiety on Male Lower Urinary Tract Symptoms: Results from the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN). J Urol. 2022 Jul;208(1):155-163. doi: 10.1097/JU.0000000000002493. Epub 2022 Feb 25.

Reference Type: BACKGROUND

PMID: 35212573 (View on PubMed)

Liu G, Andreev VP, Helmuth ME, Yang CC, Lai HH, Smith AR, Wiseman JB, Merion RM, Erickson BA, Cella D, Griffith JW, Gore JL, DeLancey JOL, Kirkali Z; LURN Study Group. Symptom Based Clustering of Men in the LURN Observational Cohort Study. J Urol. 2019 Dec;202(6):1230-1239. doi: 10.1097/JU.0000000000000354. Epub 2019 May 23.

Reference Type: BACKGROUND

PMID: 31120372 (View on PubMed)

Helfand BT, Smith AR, Lai HH, Yang CC, Gore JL, Erickson BA, Kreder KJ, Cameron AP, Weinfurt KP, Griffith JW, Lentz A, Talaty P, Andreev VP, Kirkali Z; LURN. Prevalence and Characteristics of Urinary Incontinence in a Treatment Seeking Male Prospective Cohort: Results from the LURN Study. J Urol. 2018 Aug;200(2):397-404. doi: 10.1016/j.juro.2018.02.075. Epub 2018 Mar 1.

Reference Type: BACKGROUND

PMID: 29477718 (View on PubMed)

Helfand BT, Glaser AP, Kasraeian A, Sterious S, Talaty P, Alcantara M, Alcantara KM, Higgins A, Ghiraldi E, Elterman D. Men with lower urinary tract symptoms secondary to BPH undergoing Aquablation with very large prostates (> 150 mL). Can J Urol. 2021 Dec;28(6):10884-10888.

Reference Type: BACKGROUND

PMID: 34895392 (View on PubMed)

Helfand BT, Kasraeian A, Sterious S, Glaser AP, Talaty P, Alcantara M, Alcantara KM, Higgins A, Ghiraldi E, Elterman DS. How I do it: Aquablation in very large prostates (> 150 mL). Can J Urol. 2022 Apr;29(2):11111-11115.

Reference Type: BACKGROUND

PMID: 35429430 (View on PubMed)

McConnell JD, Bruskewitz R, Walsh P, Andriole G, Lieber M, Holtgrewe HL, Albertsen P, Roehrborn CG, Nickel JC, Wang DZ, Taylor AM, Waldstreicher J. The effect of finasteride on the risk of acute urinary retention and the need for surgical treatment among men with benign prostatic hyperplasia. Finasteride Long-Term Efficacy and Safety Study Group. N Engl J Med. 1998 Feb 26;338(9):557-63. doi: 10.1056/NEJM199802263380901.

Reference Type: BACKGROUND

PMID: 9475762 (View on PubMed)

McConnell JD, Roehrborn CG, Bautista OM, Andriole GL Jr, Dixon CM, Kusek JW, Lepor H, McVary KT, Nyberg LM Jr, Clarke HS, Crawford ED, Diokno A, Foley JP, Foster HE, Jacobs SC, Kaplan SA, Kreder KJ, Lieber MM, Lucia MS, Miller GJ, Menon M, Milam DF, Ramsdell JW, Schenkman NS, Slawin KM, Smith JA; Medical Therapy of Prostatic Symptoms (MTOPS) Research Group. The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med. 2003 Dec 18;349(25):2387-98. doi: 10.1056/NEJMoa030656.

Reference Type: BACKGROUND

PMID: 14681504 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 14767299 (View on PubMed)

Setia SA, Smith J, Cendo D, Yoder J, Gorin MA, Allaway MJ, Vourganti S. Outcomes of freehand transperineal prostate biopsy with omission of antibiotic prophylaxis. BJU Int. 2022 Jul;130(1):54-61. doi: 10.1111/bju.15590. Epub 2021 Dec 23.

Reference Type: BACKGROUND

PMID: 34491606 (View on PubMed)

Lightner DJ, Wymer K, Sanchez J, Kavoussi L. Best Practice Statement on Urologic Procedures and Antimicrobial Prophylaxis. J Urol. 2020 Feb;203(2):351-356. doi: 10.1097/JU.0000000000000509. Epub 2019 Aug 23.

Reference Type: BACKGROUND

PMID: 31441676 (View on PubMed)

He J, Guo Z, Huang Y, Wang Z, Huang L, Li B, Bai Z, Wang S, Xiang S, Gu C, Pan J. Comparisons of efficacy and complications between transrectal and transperineal prostate biopsy with or without antibiotic prophylaxis. Urol Oncol. 2022 May;40(5):191.e9-191.e14. doi: 10.1016/j.urolonc.2022.01.004. Epub 2022 Feb 12.

Reference Type: BACKGROUND

PMID: 35168882 (View on PubMed)

Ahmed Ali U, Martin ST, Rao AD, Kiran RP. Impact of preoperative immunosuppressive agents on postoperative outcomes in Crohn's disease. Dis Colon Rectum. 2014 May;57(5):663-74. doi: 10.1097/DCR.0000000000000099.

Reference Type: BACKGROUND

PMID: 24819109 (View on PubMed)

Quaresma AB, Yamamoto T, Kotze PG. Biologics and surgical outcomes in Crohn's disease: is there a direct relationship? Therap Adv Gastroenterol. 2020 Jul 16;13:1756284820931738. doi: 10.1177/1756284820931738. eCollection 2020.

Reference Type: BACKGROUND

PMID: 32728389 (View on PubMed)

Hyman NH, Cheifetz AS. PUCCINI: Safety of Anti-TNF in the Perioperative Setting. Gastroenterology. 2022 Jul;163(1):44-46. doi: 10.1053/j.gastro.2022.04.050. Epub 2022 May 4. No abstract available.

Reference Type: BACKGROUND

PMID: 35525321 (View on PubMed)

Cohen BL, Fleshner P, Kane SV, Herfarth HH, Palekar N, Farraye FA, Leighton JA, Katz JA, Cohen RD, Gerich ME, Cross RK, Higgins PDR, Tinsley A, Glover S, Siegel CA, Bohl JL, Iskandar H, Ji J, Hu L, Sands BE. Prospective Cohort Study to Investigate the Safety of Preoperative Tumor Necrosis Factor Inhibitor Exposure in Patients With Inflammatory Bowel Disease Undergoing Intra-abdominal Surgery. Gastroenterology. 2022 Jul;163(1):204-221. doi: 10.1053/j.gastro.2022.03.057. Epub 2022 Apr 10.

Reference Type: BACKGROUND

PMID: 35413359 (View on PubMed)

Bechara FG, Podda M, Prens EP, Horvath B, Giamarellos-Bourboulis EJ, Alavi A, Szepietowski JC, Kirby J, Geng Z, Jean C, Jemec GBE, Zouboulis CC. Efficacy and Safety of Adalimumab in Conjunction With Surgery in Moderate to Severe Hidradenitis Suppurativa: The SHARPS Randomized Clinical Trial. JAMA Surg. 2021 Nov 1;156(11):1001-1009. doi: 10.1001/jamasurg.2021.3655.

Reference Type: BACKGROUND

PMID: 34406349 (View on PubMed)

Related Links

https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/125057s0276lbl.pdf

HIGHLIGHTS OF PRESCRIBING INFORMATION

Other Identifiers

R01DK135516

Identifier Type: NIH

Identifier Source: secondary_id

View Link

EH22-232

Identifier Type: -

Identifier Source: org_study_id