Effects of TNF Blockade on Human BPH/LUTS
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 70
- 试验地点
- 1
- 主要终点
- International Prostate Symptom Score
研究概览
简要总结
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.
详细描述
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").
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
盲法说明
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.
入排标准
- 年龄范围
- 45 Years 至 80 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Age 45-80 years
- •Diagnosed by physician with BPH
- •Prostate volume ≥ 60mL
- •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
排除标准
- •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
研究组 & 干预措施
adalimumab
adalimumab 40 mg every 2 weeks
干预措施: Adalimumab (Drug)
结局指标
主要结局
International Prostate Symptom Score
时间窗: 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
时间窗: Through study completion (Week 24)
Frequency and severity of treatment related adverse events will be reported using the Clavien-Dindo severity grading system.
次要结局
- Change in prostate volume(12 weeks)
- The Patient-Reported Outcomes Measurement Information System (PROMIS-29) Profile v2.1(The past 7 days)
- 3-Day Voiding Diary(Recorded on three separate days)
- Change in maximum flow rate (uroflowmetry)(Through study completion (Week 24))
- LURN Symptom Index 29 (LURN SI-29)(The past 7 days)
- Change in PVR (post-void residual)(Through study completion (Week 24))
- Patient Global Impression of Improvement (PGI-I)(Through study completion (Week 24))
- Change in systemic markers of inflammation (ESR, CRP)(12 weeks)
研究者
Alexander Glaser
M.D.; Clinical Assistant Professor University of Chicago Pritzker School of Medicine
NorthShore University HealthSystem