Microbiomes of Pelvic Pain
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01738464|
Recruitment Status : Recruiting
First Posted : November 30, 2012
Last Update Posted : February 27, 2018
|Condition or disease|
|Interstitial Cystitis Chronic Prostatitis Chronic Pelvic Pain Syndrome Lower Urinary Tract Symptoms Overactive Bladder Major Depression|
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.
|Study Type :||Observational|
|Estimated Enrollment :||300 participants|
|Official Title:||Microbiomes of Pelvic Pain|
|Study Start Date :||June 2012|
|Estimated Primary Completion Date :||March 7, 2019|
|Estimated Study Completion Date :||March 8, 2019|
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.
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 patients will be compared to Controls and Pelvic Pain cohorts.
- 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01738464
|Contact: David J Klumpp, PhDfirstname.lastname@example.org|
|Contact: Anthony J Schaeffer, MDemail@example.com|
|United States, Illinois|
|Chicago, Illinois, United States, 60611|
|Principal Investigator:||David J Klumpp, PhD||Northwestern University|