Interstitial Cystitis: Examination of the Central Autonomic Network
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 72
- 试验地点
- 2
- 主要终点
- Total Score on Genitourinary Pain Index (GUPI) Scale
研究概览
简要总结
This proposal aims to move the science of chronic pelvic pain (CPP) from simple associations towards an investigation of cause and effect relationships. The investigators will determine whether the striking changes in autonomic nervous system responsiveness (ANS-R) contribute meaningfully to the pathogenesis of CPP.
详细描述
This multi-site trial will recruit 2 groups of female subjects ages 18-80 years, evenly distributed across decades (10 or 20 per decade as appropriate): Chronic pelvic pain (CPP) and Healthy Controls (HC). The chronic pelvic pain group will be split into 2 sub groups where some participants will receive metopropol then placebo while the other participants in this interventional group will receive placebo then metoprolol.
This proposal aims to move the science of chronic pelvic pain (CPP) from simple associations towards an investigation of cause and effect relationships. We will determine whether the striking changes in ANS-R contribute meaningfully to the pathogenesis of CPP through 3 aims:
- Careful longitudinal repeated measures in individual subjects to determine if ANS-R changes precede clinical changes;
- Assessing the impact of an intervention designed to change ANS-R on the clinical course of CPP;
- Evaluating changes in brain connectivity between the prefrontal cortex (PFC) and the periaqueductal gray (PAG) associated with changes in ANS-R and improved disease status.
Subjects will be pre-screened in person or on the phone. An in-person pre-screen takes place in the MCW Neurology Research Rooms at Froedtert Hospital. If the subject is able to participate, subject will sign the informed consent form before completing a baseline evaluation. The baseline evaluation occurs either following consent or at another date convenient for them. Subjects must complete all baseline activities within 2 weeks, or before their Week 4/Visit 2. The baseline evaluation is comprised of a general examination, a set of questionnaires, background history documenting date of diagnosis, medications tried, duration of each treatment and dosing, surgeries and therapeutic and exploratory procedures performed. A pelvic examination will be performed with CPP subjects patients only. Active Change in Posture (ACP) is administered to the subject. Subjects will complete the uroflow (urine) measurement and Valsalva maneuver in the MCW Neurology Research Rooms with a member of the research team present.
Observational Substudy:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- Double (Participant, Investigator)
盲法说明
Participants and investigator did not know if they were randomized to intervention or placebo first for Chronic pelvic pain group
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Women aged between 18 and 80 years old
- •Healthy controls; Patients diagnosed with Interstitial cystitis/Painful bladder syndrome (IC/BPS) or Myofascial pelvic pain (MPP)
- •IC/BPS - ≥3 months chronic pelvic pain, pressure or discomfort perceived to be related to the urinary bladder accompanied by at least one other urinary symptom like persistent urge to void or frequency. Confusable diseases as the cause of the symptoms must be excluded, particularly recurrent UTI
- •MPP - ≥3 months of non-cyclic continuous pelvic pain unrelated to bladder state and a minimum of 2 of 5 examined pelvic floor TPs scoring at least 4 out of 10 on a numeric rating scale using 2 kg pressure applied with the index finger
- •Provision of informed consent prior to any study specific procedures
排除标准
- •Known nervous system conditions including but not limited to diabetic neuropathy, Parkinson's disease, Alzheimer's disease, multiple sclerosis, strokes, seizures, etc.
- •Baseline heart rate < 50 bpm; blood pressure ≥ 140/80 mmHg at rest or uncontrolled hypertension; or hypertension requiring more than two drugs for control
- •Pregnant, attempting to become pregnant , or breast-feeding
- •Unevaluated hematuria or infection at the time of enrollment
- •Pelvic or bladder neoplasm or infection
- •Severe asthma, inflammatory arthritis, connective tissue or auto-immune disorders
- •Evidence of unstable medical disorder such as kidney (rising creatinine or end-stage renal failure) or liver impairment (rising AST or ALT, or end-stage with coagulopathy); poorly controlled significant cardiovascular (CHF), respiratory, endocrine (diabetes - A1c > 9 - or untreated thyroid dysfunction) or uncontrolled psychiatric illness (such as untreated depression, psychosis, etc.)
- •Treatment with a drug or medical device within the previous 30 days that has not received regulatory approval
- •Use of hormones (except insulin, thyroid replacement or oral contraceptives). Hormone replacement therapy is acceptable
- •Current, ongoing drug or alcohol abuse
- •Current use of 150 mg or more of narcotics or morphine equivalent (or inconsistent dosages or frequency - varying by > 50 mg morphine equivalent per day)
- •Previous augmentation cystoplasty, cystectomy, cytolysis, or neurectomy. Pelvic surgery in the last 6 months.
- •Any major surgical intervention with general anesthesia in the last 90 days. Current use of anticholinergic medications.
- •Current use of beta-blocker(s).
- •Unwillingness to take a beta blocker and placebo, or planned use of beta-blocker(s) other than study medication.
- •Previous allergic or serious reaction to beta-blockers. Initiation of neural stimulator in the last 30 days.
- •Any on-going or pending medical, health or disability related litigation, or current pursuit of disability.
- •Any condition that in the judgment of the investigator and the internal advisory panel would interfere with the patient's ability to provide informed consent, comply with study instructions, place the patient at increased risk, or which would clearly confound the interpretation of the study results (specific reason will be documented).
- •Current participation in another clinical trial that interferes with ICECAN policies and procedures .
- •Investigators, study staff and their immediate families.
- •Inability to speak, read, and understand English.
- •Allergy to adhesives.
- •Initiation of any new treatment class in the last 30 days, or intent to initiate a new class of treatment in the study. Treatment classes include:
- •Pelvic injection
- •Pelvic floor therapy
- •Agents with specific FDA approval for IC/BPS or MPP (e.g., Elmiron)
- •Anticonvulsants
- •Tricyclic agents
- •Intravesical therapy or Botox
- •Bladder hydrodistention
研究组 & 干预措施
Chronic Pelvic Pain
Participants with chronic pelvic pain will be randomized to either take 8 weeks of Metoprolol Tartrate Oral Tablet, followed by a 4-Week washout period, and then 8 weeks of Placebo OR to take 8 weeks of Placebo Oral Tablet, followed by a 4-Week washout period, and then 8 weeks of Metoprolol Tartrate Oral Tablet. This intervention aims at determining whether Metoprolol reduces pain in subjects in both groups compared to placebo. Some participants were not randomized and were instead enrolled into the observational sub-study.
干预措施: Metoprolol Tartrate Oral Tablet (Drug)
Chronic Pelvic Pain
Participants with chronic pelvic pain will be randomized to either take 8 weeks of Metoprolol Tartrate Oral Tablet, followed by a 4-Week washout period, and then 8 weeks of Placebo OR to take 8 weeks of Placebo Oral Tablet, followed by a 4-Week washout period, and then 8 weeks of Metoprolol Tartrate Oral Tablet. This intervention aims at determining whether Metoprolol reduces pain in subjects in both groups compared to placebo. Some participants were not randomized and were instead enrolled into the observational sub-study.
干预措施: Placebo Oral Tablet (Drug)
Chronic Pelvic Pain
Participants with chronic pelvic pain will be randomized to either take 8 weeks of Metoprolol Tartrate Oral Tablet, followed by a 4-Week washout period, and then 8 weeks of Placebo OR to take 8 weeks of Placebo Oral Tablet, followed by a 4-Week washout period, and then 8 weeks of Metoprolol Tartrate Oral Tablet. This intervention aims at determining whether Metoprolol reduces pain in subjects in both groups compared to placebo. Some participants were not randomized and were instead enrolled into the observational sub-study.
干预措施: No intervention- observational sub-study (Other)
结局指标
主要结局
Total Score on Genitourinary Pain Index (GUPI) Scale
时间窗: Weeks 4, 12 and 24
The total GUPI score is calculated from the sum of the 3 scores from the subscales. There is no uniformity in the ranges of scores for the individual questions. The 3 subscales are: pain, urinary, and quality of life. The total score range can go from 0-45. The higher the score indicates more female urinary symptoms. Scores were calculated for each participant at weeks 4 (baseline), 12 (post-first intervention) and 24 (post-second intervention) of their participation in the study.
Average Score on the First Domain of the Multidimensional Pain Scoring (MPI) Scale
时间窗: Weeks 4, 12 and 24
The average score comes from the Pain Experience, the first domain, of the MPI. Domain 1 includes five scales designed to measure important dimensions of the chronic pain experience including; 1) perceived interference of pain in vocational, social/recreational, and family/marital functioning, 2) support or concern from spouse or significant other, 3) pain severity, 4) perceived life control, and 5) affective distress. Higher scores indicate more impactful effects of the pain experience in daily life. Responses from individual questions range from 0-6. 0 indicated no pain/no interference/no change. 6 indicates very intense pain/extreme interference/extreme change. The final total score range is 0-6 with 0 being absent pain and 6 being the worst pain rating. A lower score is better. Scores were calculated for each participant at weeks 4 (baseline), 12 (post-first intervention) and 24 (post-second intervention) of their participation in the study.
次要结局
未报告次要终点
研究者
Thomas Chelimsky, MD
Director, VCU Comprehensive Autonomic Center; Director, 4PCP Curriculum (Primary Practice Practitioner Program for Chronic Pain)
Virginia Commonwealth University