Irritable Bowel Syndrome and Control Volunteers: Diet Challenge

Sponsor

Indiana University (Other)

Overall Status

Recruiting

CT.gov ID

NCT03983434

Collaborator

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

Enrollment

Location

Arms

37.6

Anticipated Duration (Months)

1.9

Patients Per Site Per Month

Study Details

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	Phase
IBS - Irritable Bowel Syndrome	Dietary Supplement: Inulin	Early Phase 1

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:

Interventional

Anticipated Enrollment :

72 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

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 :

Aug 13, 2019

Anticipated Primary Completion Date :

May 31, 2022

Anticipated Study Completion Date :

Sep 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.
Experimental: 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.
Experimental: 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.

Arm

Intervention/Treatment

Experimental: 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.

Experimental: 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.

Experimental: 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

Total fecal bile acids [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
Total fecal short chain fatty acids [48 hours]
Stool samples will be collected for measurement of measurement of short chain fatty acids (µg/mg) by liquid chromatography-mass spectrometry
Individual fecal short chain fatty acids [48 hours]
Stool samples will be collected for measurement of measurement of short chain fatty acids (µg/mg) by liquid chromatography-mass spectrometry
Fecal microbial population [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
Fecal inulin [48 hours]
Fecal inulin content will be measured using short acid hydrolysis and high-performance liquid chromatography

Secondary Outcome Measures

Percent primary fecal bile acids [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.
Stool characteristics [4 days]
Stool characteristics will be measured using a 4 day bowel diary

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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 except for C-section, tubal ligation, vaginal hysterectomy and 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
Regular use of tobacco products within the past 6 months.