Irritable Bowel Syndrome and Control Volunteers: Diet Challenge

• ClinicalTrials.gov Identifier: NCT03983434
• Recruitment Status: Recruiting
• First Posted: June 12, 2019
• Last Update Posted: February 9, 2021
• Sponsor: Indiana University
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Information provided by (Responsible Party): Andrea Shin, Indiana University

Study Description

Brief Summary:

The purpose of this study is to study the relationship between the bile acids, short chain fatty acids and bacteria within the intestines. The hypothesis is that changes in the bacterial composition of the stool are associated with the differences in bile acids and short chain fatty acids in patients having irritable bowel syndrome compared to healthy individuals.

Condition or disease	Intervention/treatment
IBS - Irritable Bowel Syndrome	Dietary Supplement: Inulin

Detailed Description:

The Study involves 3 visits and will in include 3 types of subjects - those who have irritable bowel syndrome (IBS) with constipation (IBS-C), IBS with diarrhea (IBS-D) and those who have no IBS symptoms or diagnosis.

Visit 1

• Volunteers will read and sign this informed consent after all questions about the study have been answered
• This is a screening visit and we may determine that volunteers ineligible to continue to participate in the study.
• Volunteers will have a medical history taken including demographics, history of symptoms and illness
• Volunteers will be asked about all medications
• A physical exam will be performed by the physician.
• Vital signs will be measured.
• Urine Pregnancy test may be done for woman in the reproductive age range.
• Eligible participants will be provided with a take-home lasagna meal.
• Participants will be given instructions and supplies for collection, storage and transportation of stool for the next visit.
• Participants will be provided with instructions for a low fiber, high fat diet which should be consumed for 2 days before stool collection and during the 2 days of stool collection. Instructions will also come with materials to allow participants to record diet intake during these 4 days.
• Participants will be provided a bowel pattern diary to record bowel symptoms over the course of the study

Day 1: this may be the same as Visit 1 or it may be a different day. It will depend upon the day that participants can make it back to the clinic for the Day 5 visit.

Day 2-4 (at home):

• Participants record stool symptoms and patterns in a diary daily starting from Day 2 to Day 5.
• During this time, participants will be instructed to consume a low fiber diet, avoid alcohol, and start a 4-day 100 g fat diet.
• On the evening before Day 5, a standardized, completely digestible, and non-fermentable meal (lasagna) will be consumed which will be provided to you on Day 1.
• Participants will collect stool at home on Day 4 and 5 and store as per instructions provided on Visit 1. They will

Day 5 (Visit 2):

• Participants return to the clinic on Day 5 after an overnight fast.
• You will receive a standard breakfast and lasanga meal with 10 g inulin (Orafti®) powder and 200 mL of water.
• Take-home meals will be provided (white bread sandwich with ham or cheese) to be consumed at 4 and 8 hours after breakfast.

Day 6 (Visit 3):

• Participants will return to the clinic in order to return stool collections and the daily diaries.
• Participants may also submit diaries by fax or email.

Study Design

• Study Type: Observational
• Estimated Enrollment: 150 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Fecal Bile Acids, Fecal Short Chain Fatty Acids and the Intestinal Microbiota in Patients With Irritable Bowel Syndrome (IBS) and Control Volunteers: Diet Challenge
• Actual Study Start Date: September 1, 2019
• Estimated Primary Completion Date: June 30, 2021
• Estimated Study Completion Date: June 30, 2023

Groups and Cohorts

Group/Cohort	Intervention/treatment
Healthy volunteers; Adults ages 18-65 years with no prior history of gastrointestinal diseases or symptoms.	Dietary Supplement: Inulin; Inulin ingestion is not being used to diagnose, treat, or prevent IBS. Inulin is being used to study an individual's ability to ferment dietary fiber.
Irritable Bowel Syndrome Patients with Diarrhea; Patients with irritable bowel syndrome (IBS) with diarrhea, ages 18-65 years fulfilling Rome IV criteria for IBS	Dietary Supplement: Inulin; Inulin ingestion is not being used to diagnose, treat, or prevent IBS. Inulin is being used to study an individual's ability to ferment dietary fiber.
Irritable Bowel Syndrome Patients with Constipation; Patients with irritable bowel syndrome (IBS) with constipation, ages 18-65 years fulfilling Rome IV criteria for IBS	Dietary Supplement: Inulin; Inulin ingestion is not being used to diagnose, treat, or prevent IBS. Inulin is being used to study an individual's ability to ferment dietary fiber.

Outcome Measures

Primary Outcome Measures :

1. Total fecal bile acids [ Time Frame: 48 hours ]
   Stool samples will be collected over 2 days for measurement of fecal bile acids (µmol/48h) by high performance liquid chromatography-mass spectometry
2. Total fecal short chain fatty acids [ Time Frame: 48 hours ]
   Stool samples will be collected for measurement of measurement of short chain fatty acids (µg/mg) by liquid chromatography-mass spectrometry
3. Individual fecal short chain fatty acids [ Time Frame: 48 hours ]
   Stool samples will be collected for measurement of measurement of short chain fatty acids (µg/mg) by liquid chromatography-mass spectrometry
4. Fecal microbial population [ Time Frame: 48 hours ]
   Stool samples will be be collected from participants for nucleic acid extraction, 16S allele PCR and sequencing to measure microbial communities and profiles of specimens
5. Fecal inulin [ Time Frame: 48 hours ]
   Fecal inulin content will be measured using short acid hydrolysis and high-performance liquid chromatography

Secondary Outcome Measures :

1. Percent primary fecal bile acids [ Time Frame: 48 hours ]
   Stool samples will be collected over 2 days for measurement of fecal bile acids (µmol/48h) by high performance liquid chromatography-mass spectrometry.
2. Stool characteristics [ Time Frame: 4 days ]
   Stool characteristics will be measured using a 4 day bowel diary

Biospecimen Retention:   Samples With DNA

Sample Collection: Stool samples will be collected from all participants after study initiation. Samples will be collected during the last 2 days of a 4-day low fiber, 100 g fat diet. Stool will be refrigerated by participants and brought to the laboratory on ice within 4 days of collection. Once received, stool specimens will be homogenized and split into 4 samples for fecal microbial, fecal SCFA, fecal inulin, and fecal bile acid analysis and immediately frozen at -80ο Celsius.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Sampling Method: Non-Probability Sample

Study Population

The target study population will be patients with IBS (both diarrhea- and constipation-predominant) and healthy controls. Participants may be identified by review of ICD10 codes, the electronic medical record, the Indiana University Motility Diagnosis Registry, and by public advertisement. Participants may also be identified and invited during clinical visits to any Indiana University site. Participants may also be recruited from the local community, the Indiana CTSI Research Network, Regenstrief Data Core, and the national ResearchMatch research registry.

Criteria

Inclusion Criteria:

• Patients with IBS, ages 18-65 fulfilling Rome IV criteria and asymptomatic controls with no prior history of GI disease or symptoms.
• Participants should be on a stable and consistent diet regimen and should not be following an extreme diet intervention such as gluten-free or a low FODMAP diet at the time of study participation.

Exclusion Criteria:

• Participants with microscopic/lymphocytic/collagenous colitis, inflammatory bowel disease, celiac disease, visceral cancer, chronic infectious disease, immunodeficiency, uncontrolled thyroid disease, history of liver disease or history of elevated AST/ALT > 2.0x the upper limit of normal
• Prior radiation therapy of the abdomen or abdominal surgeries with the exception of appendectomy or cholecystectomy > 6 months prior to study initiation
• Ingestion of any prescription, over the counter, or herbal medications which can affect GI transit or study interpretation (e.g. opioids, narcotics, anticholinergics, norepinephrine reuptake inhibitors, nonsteroidal anti-inflammatory drugs, COX-2 inhibitors, bile acid sequestrants) within 6 months of study initiation for asymptomatic volunteers or within 2 days before study initiation for IBS patients. Rescue therapy to facilitate stool collection will be permitted where needed.
• Any females who are pregnant or trying to become pregnant or breast-feeding
• Antibiotic usage within 3 months prior to study participation
• Prebiotic or probiotic usage within the 2 weeks prior to study initiation
• Use of tobacco products within the past 6 months.

Contacts and Locations

Contacts

Contact: Tonya Hamilton; 317-278-9296; tpinksto@iu.edu

Contact: Anita Gupta; 317-948-9227 ext 3179489227; anigupta@iu.edu

Locations

United States, Indiana

Indiana University; Recruiting

Indianapolis, Indiana, United States, 46202

Contact: Tonya Hamilton 317-278-9296 tpinksto@iu.edu

Sponsors and Collaborators

Indiana University

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

More Information

• Responsible Party: Andrea Shin, Assistant Professor, Indiana University
• ClinicalTrials.gov Identifier: NCT03983434
• Other Study ID Numbers: 1903209172; K23DK122015 ( U.S. NIH Grant/Contract )
• First Posted: June 12, 2019
• Last Update Posted: February 9, 2021
• Last Verified: February 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Andrea Shin, Indiana University:

microbiome; microbiota; short chain fatty acids; prebiotic; bile acids

Additional relevant MeSH terms:

Irritable Bowel Syndrome; Syndrome; Disease; Pathologic Processes; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases