Benign Prostatic Hyperplasia (BPH)
Conditions
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).
Interventions
DRUGAdalimumab
Adalimumab will be delivered subcutaneously (under the skin) at a dose of 40mg every 2 weeks for a total of 6 doses.
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Endeavor Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Masking description
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.
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.
Eligibility
Sex/Gender
MALE
Age
45 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| International Prostate Symptom Score | 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). |
| Safety as measured by Clavien-Dindo grading system | Through study completion (Week 24) | Frequency and severity of treatment related adverse events will be reported using the Clavien-Dindo severity grading system. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Patient-Reported Outcomes Measurement Information System (PROMIS-29) Profile v2.1 | 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). |
| Patient Global Impression of Improvement (PGI-I) | 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. |
| 3-Day Voiding Diary | 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. |
| Change in PVR (post-void residual) | Through study completion (Week 24) | Bladder scanner to measure post-void residual |
| Change in prostate volume | 12 weeks | Prostate volume as calculated by MRI prostate before and after adalimumab/placebo treatment |
| Change in systemic markers of inflammation (ESR, CRP) | 12 weeks | Blood test for systemic markers of inflammation (erythrocyte sedimentation rate \[ESR\] and c-reactive protein \[CRP\]) before and after adalimumab/placebo treatment |
| Change in maximum flow rate (uroflowmetry) | 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. |
| LURN Symptom Index 29 (LURN SI-29) | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Cellular consequences of adalimumab therapy on prostate tissue | 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. |
| Genetic predictors to stratify patients with differential response to adalimumab | 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 |
Countries
United States
Contacts
Primary ContactMalgorzata Antoniak, Ph.D.
Backup ContactPooja Talaty, MS MHA CCRP
Outcome results
None listed