Effects of TNF Blockade on Human BPH/LUTS

November 18, 2024 updated by: Alexander Glaser, NorthShore University HealthSystem
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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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").

Study Type

Interventional

Enrollment (Estimated)

70

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Illinois
      • Glenview, Illinois, United States, 60026
        • Recruiting
        • Northshore University Healthsystem
        • Contact:
        • Contact:
          • Simon W Hayward, Ph.D
        • Contact:
          • Alexander P Glaser, M.D.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: adalimumab
adalimumab 40 mg every 2 weeks
Drug: Adalimumab
Adalimumab will be delivered subcutaneously (under the skin) at a dose of 40mg every 2 weeks for a total of 6 doses.
Other Names:
  • Placebo will be administered subcutaneously every 2 weeks, for a total of 6 injections.
No Intervention: Placebo
placebo injection (saline) every 2 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
International Prostate Symptom Score
Time Frame: The past 30 days
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
Time Frame: Through study completion (Week 24)
Frequency and severity of treatment related adverse events will be reported using the Clavien-Dindo severity grading system.
Through study completion (Week 24)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
3-Day Voiding Diary
Time Frame: Recorded on three separate days
The diary records the patient's daily fluid intake, frequency of urination throughout the day and night, instances of leakage, and the quantity of lost urine. Analyzing these findings against the standard criteria for regular bladder function could reveal potential issues and help confirm a diagnosis. The definition of normal benchmarks takes into account factors like age, gender, as well as various internal and external variables including fluid consumption and its nature.
Recorded on three separate days
LURN Symptom Index 29 (LURN SI-29)
Time Frame: The past 7 days
This is a multidimensional 29-item questionnaire that assesses different lower urinary tract symptoms as well as single item about global bother.
The past 7 days
The Patient-Reported Outcomes Measurement Information System (PROMIS-29) Profile v2.1
Time Frame: The past 7 days
The PROMIS-29 Profile is a 29-item instrument that combines short assessments of eight core constructs of health-related quality of life (HRQoL): physical function (PF), sleep disturbance (SD), pain interference (PI) and pain intensity (PIN), fatigue (FA), anxiety (AN), depression (DE) and ability to participate in social roles and activities (SRAA).
The past 7 days
Patient Global Impression of Improvement (PGI-I)
Time Frame: Through study completion (Week 24)
This is a single item that captures how much better or worse the person's condition is relative to when they began treatment. Scale ranges from "Very much worse" to "Very much better".
Through study completion (Week 24)
Change in maximum flow rate (uroflowmetry)
Time Frame: Through study completion (Week 24)
Uroflowmetry is a diagnostic test that measures the rate and pattern of urine flow during voiding to assess the functioning of the urinary tract. Changes in maximum flow rate (Qmax) will be compared.
Through study completion (Week 24)
Change in PVR (post-void residual)
Time Frame: Through study completion (Week 24)
Bladder scanner to measure post-void residual
Through study completion (Week 24)
Change in prostate volume
Time Frame: 12 weeks
Prostate volume as calculated by MRI prostate before and after adalimumab/placebo treatment
12 weeks
Change in systemic markers of inflammation (ESR, CRP)
Time Frame: 12 weeks
Blood test for systemic markers of inflammation (erythrocyte sedimentation rate [ESR] and c-reactive protein [CRP]) before and after adalimumab/placebo treatment
12 weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cellular consequences of adalimumab therapy on prostate tissue
Time Frame: Through study completion (Week 24)
We hypothesize that TNF-antagonist treatment will de-repress apoptosis, suppress proliferative pathways, and modify the immune cell profile in the prostate. In this aim we will employ flow cytometry and scRNA-seq analysis with pathway imputation, supplemented with immunohistochemistry and bulk RNA-seq, to characterize these changes at a cellular and tissue level.
Through study completion (Week 24)
Genetic predictors to stratify patients with differential response to adalimumab
Time Frame: Through study completion (Week 24)
We hypothesize that genetic variants in 1) genes involved in the TNF-antagonist targeted pathways, 2) susceptibility to chronic inflammation, and 3) susceptibility to BPH influence the effectiveness of the therapy
Through study completion (Week 24)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

NorthShore University HealthSystem

Collaborators

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

Investigators

  • Principal Investigator: Alexander P Glaser, M.D., Northshore University Healthsystem
  • Principal Investigator: Simon W Hayward, Ph.D., Northshore University Healthsystem

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 24, 2024

Primary Completion (Estimated)

April 1, 2028

Study Completion (Estimated)

June 1, 2028

Study Registration Dates

First Submitted

August 29, 2023

First Submitted That Met QC Criteria

September 25, 2023

First Posted (Actual)

October 2, 2023

Study Record Updates

Last Update Posted (Estimated)

November 21, 2024

Last Update Submitted That Met QC Criteria

November 18, 2024

Last Verified

November 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EH22-232
  • R01DK135516 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Reporting of results in ClinicalTrials.gov

IPD Sharing Time Frame

08/10/2023 to June 1,2028

IPD Sharing Access Criteria

Reporting of results in ClinicalTrials.gov Sharing of study data per NIH policies

IPD Sharing Supporting Information Type

  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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