Clinical trial NCT06062875: Effects of TNF Blockade on Human BPH/LUTS
Official title: Effects of TNF Blockade on Human BPH/LUTS
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Benign Prostatic Hyperplasia (BPH)
Lead sponsor: Endeavor Health
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2023-10-02
Enrollment: 70
Sex: MALE
Minimum age (years): 45
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model 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.
Primary purpose: BASIC_SCIENCE

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").

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

Primary outcomes:
measure: International Prostate Symptom Score
timeFrame: The past 30 days
measure: Safety as measured by Clavien-Dindo grading system
timeFrame: Through study completion (Week 24)
Secondary outcomes:
measure: LURN Symptom Index 29 (LURN SI-29)
timeFrame: The past 7 days
measure: The Patient-Reported Outcomes Measurement Information System (PROMIS-29) Profile v2.1
timeFrame: The past 7 days
measure: Patient Global Impression of Improvement (PGI-I)
timeFrame: Through study completion (Week 24)
measure: 3-Day Voiding Diary
timeFrame: Recorded on three separate days
measure: Change in maximum flow rate (uroflowmetry)
timeFrame: Through study completion (Week 24)
measure: Change in PVR (post-void residual)
timeFrame: Through study completion (Week 24)
measure: Change in prostate volume
timeFrame: 12 weeks
measure: Change in systemic markers of inflammation (ESR, CRP)
timeFrame: 12 weeks
Other outcomes:
measure: Cellular consequences of adalimumab therapy on prostate tissue
timeFrame: Through study completion (Week 24)
measure: Genetic predictors to stratify patients with differential response to adalimumab
timeFrame: Through study completion (Week 24)
Locations:
city: Glenview
country: United States
facility: NorthShore University HealthSystem
state: Illinois
Study officials:
affiliation: Endeavor Health
name: Simon W Hayward, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Endeavor Health
name: Alexander P Glaser, M.D.
role: PRINCIPAL_INVESTIGATOR
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