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Microbiomes of Pelvic Pain

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2017 by Northwestern University
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
David Klumpp, Northwestern University
ClinicalTrials.gov Identifier:
NCT01738464
First received: November 28, 2012
Last updated: March 13, 2017
Last verified: March 2017
  Purpose
This research study seeks to provide more insight as to how the microbiome affects or is affected by conditions causing chronic pelvic pain such as Interstitial Cystitis (IC), Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS), Lower Urinary Tract Symptoms (LUTS), or Overactive bladder (OAB). Depression and many chronic pain disorders are often related and are poorly understood, and treatment is often not helpful. The goal of this study is to explain pelvic pain characteristics and causes by studying microbiomes of healthy people compared to people suffering from IC, CP/CPPS, LUTS, OAB, and Major depression.

Condition
Interstitial Cystitis
Chronic Prostatitis
Chronic Pelvic Pain Syndrome
Lower Urinary Tract Symptoms
Overactive Bladder
Major Depression

Study Type: Observational
Study Design: Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Microbiomes of Pelvic Pain

Resource links provided by NLM:


Further study details as provided by Northwestern University:

Primary Outcome Measures:
  • Genotype Anaerobic Bacterial populations between Control patients and patients diagnosed with Interstitial Cystitis or Chronic Prostatitis/Chronic Pelvic Pain Syndrome, Lower Urinary Tract Symptoms, Overactive Bladder, and Major Depression [ Time Frame: 1 day ]
    Anaerobic bacteria will be collected from a fecal specimen from both Control patients and patients diagnosed with Interstitial Cystitis or Chronic Prostatitis/Chronic Pelvic Pain Syndrome, Lower Urinary Tract Symptoms, Overactive Bladder, and/or Major Depression. Genotyping will be done to differentiate bacterial populations between the Control patients and patients with Interstitial Cystitis or Chronic Prostatitis/Chronic Pelvic Pain Syndrome, Lower Urinary Tract Symptoms, Overactive Bladder, and/or Major Depression.

  • Separate serum from blood specimen given by Control patients and patients diagnosed with Interstitial Cystitis or Chronic Prostatitis/Chronic Pelvic Pain Syndrome, Lower Urinary Tract Symptoms, Overactive Bladder, and Major Depression [ Time Frame: 3 days ]
    If you are a local patient: Blood will be collected and serum will be separated and analyzed for HPA markers associated with the anaerobic organisms found in the microbiome.

  • Collect urine specimen from Control patients and patients diagnosed with Interstitial Cystitis or Chronic Prostatitis/Chronic Pelvic Pain Syndrome, Lower Urinary Tract Symptoms, Overactive Bladder, and Major Depression [ Time Frame: 3 days ]
    If you are a local patient: Urine will be analyzed for the presence of bacteria, and HPA markers associated with the organisms found in the microbiome.


Biospecimen Retention:   Samples With DNA
Stool specimen, Blood/Serum specimen, Urine specimen

Estimated Enrollment: 300
Study Start Date: June 2012
Estimated Study Completion Date: March 8, 2018
Estimated Primary Completion Date: March 7, 2018 (Final data collection date for primary outcome measure)
Groups/Cohorts
Pelvic Pain
Interstitial Cystitis or Chronic Prostatitis/Chronic Pelvic Pain Syndrome, Lower Urinary Tract Symptoms, and Overactive Bladder patients will be compared to Healthy and Depressed patients.
Controls
Healthy patients will be used as controls to compare to patients diagnosed with Interstitial Cystitis, Chronic Prostatitis, Chronic Pelvic Pain Syndrome, Lower Urinary Tract Symptoms, Overactive Bladder, and Depressed patients.
Major Depression
Major Depression patients will be compared to Controls and Pelvic Pain cohorts.

Detailed Description:

Interstitial cystitis/painful bladder syndrome (IC) or Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is characterized by chronic pelvic pain and voiding dysfunction. IC or CP/CPPS remains an enigma within urology, with no known etiology or widely effective therapies. However, some IC, CP/CPPS, and depressed patients suffer bowel co-morbidities, and it is well established that the GI tract can influence bladder function, mood and sensation via pelvic organ crosstalk. Like other body sites, the gut harbors a rich microflora. Studies characterizing microbial diversity and relative abundance at a particular body site, the "microbiome," reveal that microbiomes play critical roles in normal cellular and organ function, and thus this importance is emphasized with the Human Microbiome Project (HMP), an NIH Common Fund initiative. CPPS patients suffer chronic pelvic pain and dramatically lower quality of life, yet diagnostic markers and effective therapies remain elusive for these costly syndromes. IC is a debilitating condition of pelvic pain and voiding dysfunction afflicting up to 8 million U.S. women where depression is a common co-morbidity, distinct from over-active bladder (OAB) patients lacking pain. IC etiology remains unknown, but urothelial lesions and lamina propria mast cells are associated with patient symptoms. Similarly, CP/CPPS afflicts 1 in 22 men in the U.S. with pain and voiding and sexual symptoms, again distinct from patients having only irritative voiding from lower urinary tract symptoms (LUTS). And although leukocytes are observed in prostatic fluid of some patients, the etiology of CP/CPPS also remains unknown. Hypothalamic-pituitary-adrenal axis (HPA) dysfunction has been implicated in female and male patients and cats with feline IC, and thus may be common among CPPS, but a mechanism that integrates pelvic pain, voiding dysfunction, HPA activity, and depression is lacking.

Microbiomes are also dynamic and subject to skewing, and these changes are increasingly associated with diseases including Crohn's disease, ulcerative colitis, obesity, and possibly depression. Antibiotic therapies alter microbiomes, often causing temporary dysfunction and sometimes resulting in diseases such as colitis. Since IC or CP/CPPS patients often have a history of urinary tract infection (UTI), they typically receive multiple courses of antibiotics. This therapeutic history of IC or CP/CPPS patients may have adverse consequences for two reasons. First, potential skewing of the gut microbiome may alter normal sensory and functional homeostatic mechanisms, contributing to pain and voiding dysfunction. Second, an altered gut microbiome may foster uropathogen reservoir expansion, and our preliminary data demonstrate urinary E. coli isolates can induce chronic pelvic pain persisting long after microbial clearance. Together these lines of reasoning raise the provocative possibility that microbiomes contribute to IC, CP/CPPS, and depression directly by supplying uropathogens or indirectly through organ crosstalk dysfunction. Therefore, is an altered gastrointestinal tract microbiome associated with IC, CP/CPPS, and/or depression? Our team marries core NIH and NIDDK missions, digestive diseases and kidney/urologic, to address this novel question with synergistic expertise in clinical diagnosis of IC, CP/CPPS, and depression, quantifying GI tract microbiomes, and neural mechanisms of microbe-induced pelvic pain. Stool samples will be analyzed by 16S rDNA sequence and in silico metagenome analyses to identify taxa, abundance, and function. Computational tools will be used to identify taxa amenable to rapid evaluation of stool. Stool, serum, and urine will be evaluated for small molecules specific to CPPS, and these putative mediators will be tested in mice for effects on pelvic pain and urinary function.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Primary care clinic patients Community sample
Criteria

Inclusion Criteria:

  • Any sex
  • Between the ages of 18 and 60
  • Any ethnicity
  • Have provided informed consent
  • Physician diagnosis of interstitial cystitis/bladder pain syndrome (IC/BPS), interstitial cystitis/painful bladder syndrome (IC/PBS), chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), Lower Urinary Tract Symptoms, Overactive Bladder, or Major Depression.
  • Report symptoms of discomfort or pain in the pelvic or abdominal region of moderate severity for at least a three (3) month period within the last six (6) months, who have been currently diagnosed with major depression
  • Are healthy, age matched, controls.

Exclusion Criteria:

For IC/CPPS/LUTS/OAB

  • Evidence of facultative Gram negative or enterococcus with a value of ≥ 100,000 colony forming units (CFU)/milliliter in mid-stream urine (VB2)
  • Secondary chronic pain condition which would prevent a clear interpretation of the study results
  • A history of tuberculous cystitis, bladder cancer, carcinoma in situ, or urethral cancer; history of alcohol abuse, inflammatory bowel disease, pelvic radiation or systemic chemotherapy, intravesical chemotherapy, intravesical Bacillus Calmette-Guerin (BCG), active urethral stricture, ureteral calculi, urethral diverticulum, or neurological disease or disorder affecting the bladder or gut
  • Unlikely to be compliant due to unmanaged medical or psychological conditions, including neurological, psychological or speech/language problems that will interfere or prevent with their understanding of consent
  • Ability to comply with the protocol or ability to complete the study
  • Pregnant or Syndromes of Chronic Pelvic Pain (SCPP) symptoms are present only during menses
  • And if there was antibiotic use in the last 6 months

For Depressed Patients:

  • Participant is in remission or has recovered from major depression, has substance abuse in the past 6 months, has been diagnosed with any bipolar or psychotic disorder, has been diagnosed with any severe cognitive impairment or dementia, history of cancer (with the exception of skin cancer), has current major psychiatric disorder or other psychiatric or medical comorbidities that would interfere with study participation (e.g. dementia, psychosis, upcoming major surgery, lupus, active heart failure, diabetes, etc., currently has a UTI and/or has had a positive urine culture in the past 6 weeks, and if there was antibiotic use in the last 3 months.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01738464

Contacts
Contact: David J Klumpp, PhD 312.908.1996 d-klumpp@northwestern.edu
Contact: Anthony J Schaeffer, MD 312.908.9844 ajschaeffer@northwestern.edu

Locations
United States, Illinois
Northwestern University Recruiting
Chicago, Illinois, United States, 60611
Sponsors and Collaborators
Northwestern University
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
Principal Investigator: David J Klumpp, PhD Northwestern University
  More Information

Responsible Party: David Klumpp, Associate Professor, Northwestern University
ClinicalTrials.gov Identifier: NCT01738464     History of Changes
Other Study ID Numbers: STU00055668
1R01DK103769-01A1 ( US NIH Grant/Contract Award Number )
Study First Received: November 28, 2012
Last Updated: March 13, 2017

Keywords provided by Northwestern University:
Pelvic Pain
Interstitial Cystitis
Microbiome
Prostatitis
Chronic
Depression

Additional relevant MeSH terms:
Cystitis
Cystitis, Interstitial
Depression
Urinary Bladder, Overactive
Depressive Disorder, Major
Pelvic Pain
Lower Urinary Tract Symptoms
Prostatitis
Behavioral Symptoms
Urinary Bladder Diseases
Urologic Diseases
Urological Manifestations
Signs and Symptoms
Depressive Disorder
Mood Disorders
Mental Disorders
Pain
Neurologic Manifestations
Prostatic Diseases
Genital Diseases, Male

ClinicalTrials.gov processed this record on April 28, 2017