Interstitial Cystitis: Examination of the Central Autonomic Network

NCT03008382 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: HM20025835
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Interstitial Cystitis/Painful Bladder Syndrome; Myofascial Pelvic Pain

Keywords

Interstitial Cystitis; Pelvic Pain

Outcome Measures

Primary Outcomes (2)

• Total Score on Genitourinary Pain Index (GUPI) Scale

  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.

  Weeks 4, 12 and 24

• Average Score on the First Domain of the Multidimensional Pain Scoring (MPI) Scale

  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.

  Weeks 4, 12 and 24

Other Outcomes (2)

• Correlation Between the Change in Autonomic Nervous System Responsiveness (ANS-R) and the Change in the Connectivity Between Prefrontal Cortex (PFC) and Periaqueductal Gray (PAG)

  24 Weeks

• Assessing Central Autonomic Network Connectivity in Subjects With Chronic Pelvic Pain

  Baseline, 12 weeks and 24 weeks

Study Arms (2)

Chronic Pelvic Pain

OTHER

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.

Drug: Metoprolol Tartrate Oral Tablet; Drug: Placebo Oral Tablet; Other: No intervention- observational sub-study

Healthy Control Group

NO INTERVENTION

Healthy female subjects ages 18-80 with various demographic background who do not have any exclusionary diagnostic or symptomatic criteria will be recruited. Subjects will never receive any randomization or drug treatment during the entire duration of the study

Interventions

Metoprolol Tartrate Oral Tablet DRUG

Metoprolol is a beta-blocker commonly used for mild blood pressure control, and also commonly used for migraine. Subjects with IC/BPS or MPP will start metoprolol at 25 mg once daily and increase to the goal dose of 25 mg 2/day after one week and continue for 8 weeks total.

Also known as: Metoprolol

Chronic Pelvic Pain

Placebo Oral Tablet DRUG

Subjects with IC/BPS or MPP will start placebo distributed in a double-blind manner. Subjects will take placebo once daily and increase to the goal dose of 25 mg 2/day after one week and continue for 8 weeks total.

Also known as: Placebo

Chronic Pelvic Pain

No intervention- observational sub-study OTHER

Participants did not receive placebo or metoprolol during the entire duration of the study.

Chronic Pelvic Pain

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Virginia Commonwealth University: lead
• Endeavor Health: collaborator
• Case Western Reserve University: collaborator

Study Sites (2)

NorthShore University HealthSystem

Evanston, Illinois, 60201, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

MeSH Terms

Conditions

Cystitis, Interstitial; Pelvic Pain

Interventions

Metoprolol

Condition Hierarchy (Ancestors)

Cystitis; Urinary Bladder Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines

Limitations and Caveats

All diagnosed subjects were combined because of inadequate recruitment related to the COVID 19 pandemic which halted study recruitment. As a result, the study was no longer adequately powered to compare the differing groups.

Results Point of Contact

• Title: Dr. Thomas Chelimsky
• Organization: Virginia Commonwealth University

Thomas.Chelimsky@vcuhealth.org

(804) 628-4859

Study Officials

• Thomas Chelimsky, MD

  Virginia Commonwealth University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Participants and investigator did not know if they were randomized to intervention or placebo first for Chronic pelvic pain group
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, VCU Comprehensive Autonomic Center; Director, 4PCP Curriculum (Primary Practice Practitioner Program for Chronic Pain)

Model Details: Participants with Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) and/or Myofascial Pelvic Pain (MPP) will be randomized to take 8 weeks of Metoprolol Tartrate Oral Tablet or Placebo Oral Tablet, followed by a 4-Week washout period, and then 8 weeks of Placebo or Metoprolol.

Study Record Dates

• First Submitted: December 28, 2016
• First Posted: January 2, 2017
• Study Start: March 1, 2017
• Primary Completion: March 16, 2022
• Study Completion: March 16, 2022
• Last Updated: February 17, 2025
• Results First Posted: February 17, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: The participant's collected data is de-identified immediately. The blood and urine are stored in a freezer until there are enough samples to send out for analysis. Heart rate recordings are uploaded to a secure MCW storage site and shared for analysis throughout the participant's participation.
• Access Criteria: Participant data will be shared through a secured web dropbox called BOX. BOX access is paid for and controlled by the Medical College of Wisconsin (MCW). The folders containing participant data are password protected and only those who are adding to the folders or performing analysis on collected data are given access through MCW. MCW's other two recruiting sites, NorthShore University HealthSystem and Case Western Reserve University, are able to add participant data to their own site folders, and each site only has access to their participants' data. Ohio State University has access to the folder containing participants' heart rate recording to perform analysis. Blood and Urine samples are deidentified and stored at MCW until a shipment is prepared. They are then sent to the University of Pittsburgh for further analysis.

Locations

US (2)