Effects of TNF Blockade on Human BPH/LUTS

Study Overview
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Brief Summary
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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
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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).

Official Title
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Effects of TNF Blockade on Human BPH/LUTS

Conditions
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Benign Prostatic Hyperplasia (BPH)

Intervention / Treatment
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* Drug: Adalimumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male sex Age 50-75 years Diagnosed by physician with BPH Prostate volume ≥ 80mL IPSS ≥ 8 Scheduled for BPH surgery (prostatic urethral lift, water vapor thermal therapy, transurethral resection of prostate, laser vaporization or enucleation, robotic waterjet treatment, or simple prostatectomy) 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 < 50 or > 75 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

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: adalimumab<br>adalimumab 40 mg every 2 weeks | Drug: Adalimumab<br>* Adalimumab will be delivered subcutaneously (under the skin) at a dose of 40mg every 2 weeks for a total of 6 doses.<br>|
| No Intervention: Placebo<br>placebo injection (saline) every 2 weeks. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| LURN Symptom Index 29 (LURN SI-29) | 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 | 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) | 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) | 
| 3-Day Voiding Diary | 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 | 
| Change in maximum flow rate (uroflowmetry) | 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) | Bladder scanner to measure post-void residual | Through study completion (Week 24) | 
| Change in prostate volume | Prostate volume as calculated by MRI prostate before and after adalimumab/placebo treatment | 12 weeks | 
| Change in systemic markers of inflammation (ESR, CRP) | Blood test for systemic markers of inflammation (erythrocyte sedimentation rate [ESR] and c-reactive protein [CRP]) before and after adalimumab/placebo treatment | 12 weeks |