Effects of TNF Blockade on Human BPH/LUTS

NCT06062875 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: EH22-232R01DK135516
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

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.

Conditions

Benign Prostatic Hyperplasia (BPH)

Outcome Measures

Primary Outcomes (2)

• International Prostate Symptom Score

  The IPSS is a self-report measure used to assess urinary urgency, frequency, and voiding symptoms, and includes one disease-specific quality of life (QoL) question. IPSS scores ranges from 0 to 35, with higher scores indicating more severe urinary symptoms, and QoL ranges from 0 (delighted) to 6 (terrible).

  The past 30 days

• Safety as measured by Clavien-Dindo grading system

  Frequency and severity of treatment related adverse events will be reported using the Clavien-Dindo severity grading system.

  Through study completion (Week 24)

Secondary Outcomes (8)

• LURN Symptom Index 29 (LURN SI-29)

  The past 7 days

• The Patient-Reported Outcomes Measurement Information System (PROMIS-29) Profile v2.1

  The past 7 days

• Patient Global Impression of Improvement (PGI-I)

  Through study completion (Week 24)

• 3-Day Voiding Diary

  Recorded on three separate days

• Change in maximum flow rate (uroflowmetry)

  Through study completion (Week 24)

Other Outcomes (2)

• Cellular consequences of adalimumab therapy on prostate tissue

  Through study completion (Week 24)

• Genetic predictors to stratify patients with differential response to adalimumab

  Through study completion (Week 24)

Study Arms (2)

adalimumab

ACTIVE COMPARATOR

adalimumab 40 mg every 2 weeks

Drug: Adalimumab

Placebo

NO INTERVENTION

placebo injection (saline) every 2 weeks.

Interventions

Adalimumab DRUG

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

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

adalimumab

Eligibility Criteria

• Age: 45 Years - 80 Years
• Gender Eligibility Details: Men 45-80 years old with BPH
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Endeavor Health: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

NorthShore University HealthSystem

Glenview, Illinois, 60026, United States

RECRUITING

Related Publications (18)

• 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.

  PMID: 35440548 BACKGROUND

• 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.

  PMID: 17182170 BACKGROUND

• 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.

  PMID: 35212573 BACKGROUND

• 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.

  PMID: 31120372 BACKGROUND

• 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.

  PMID: 29477718 BACKGROUND

• 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.

  PMID: 34895392 BACKGROUND

• 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.

  PMID: 35429430 BACKGROUND

• 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.

  PMID: 9475762 BACKGROUND

• 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.

  PMID: 14681504 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

• 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.

  PMID: 34491606 BACKGROUND

• 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.

  PMID: 31441676 BACKGROUND

• 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.

  PMID: 35168882 BACKGROUND

• 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.

  PMID: 24819109 BACKGROUND

• 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.

  PMID: 32728389 BACKGROUND

• 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.

  PMID: 35525321 BACKGROUND

• 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.

  PMID: 35413359 BACKGROUND

• 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.

  PMID: 34406349 BACKGROUND

Related Links

• HIGHLIGHTS OF PRESCRIBING INFORMATION

MeSH Terms

Conditions

Prostatic Hyperplasia

Interventions

Adalimumab

Condition Hierarchy (Ancestors)

Prostatic Diseases; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Simon W Hayward, Ph.D.

  Endeavor Health

  PRINCIPAL INVESTIGATOR

• Alexander P Glaser, M.D.

  Endeavor Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Malgorzata Antoniak, Ph.D.

CONTACT

847-503-4282; MAntoniak@northshore.org

Pooja Talaty, MS MHA CCRP

CONTACT

847-503-4280; PTalaty@northshore.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Patients will then be randomized in a double-blind fashion to receive adalimumab 40 mg every 2 weeks or placebo injection (saline) every 2 weeks.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D.; Clinical Assistant Professor University of Chicago Pritzker School of Medicine

Model Details: 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.

Study Record Dates

• First Submitted: August 29, 2023
• First Posted: October 2, 2023
• Study Start: January 24, 2024
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: November 21, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: 08/10/2023 to June 1,2028
• Access Criteria: Reporting of results in ClinicalTrials.gov Sharing of study data per NIH policies

Locations

US (1)