Clinical trial NCT03983434: Irritable Bowel Syndrome and Control Volunteers: Diet Challenge
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: IBS - Irritable Bowel Syndrome
Keywords: microbiome
microbiota
short chain fatty acids
prebiotic
bile acids
Lead sponsor: Indiana University
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2019-06-12
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.

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.

Day 30-90

• Optional dietary follow-up (Day 30-90): To further assess the utility of the 24 hour dietary recall, willing participants will be invited to participate in a an optional follow-up activity during which they will complete the Automated Self-Administered Dietary Assessment Tool with or without assistance of a trained interviewer. Interested volunteers will be contacted by phone and provided instructions on how to complete the tool online by the study team.

Eligibility 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 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.

Primary outcomes:
measure: Total Fecal Bile Acids
timeFrame: 48 hours
measure: Total Fecal Short Chain Fatty Acids
timeFrame: 48 hours
measure: Individual Fecal Short Chain Fatty Acids - Acetate
timeFrame: 48 hours
measure: Individual Fecal Short Chain Fatty Acids - Propionate
timeFrame: 48 hours
measure: Individual Fecal Short Chain Fatty Acids - Butyrate
timeFrame: 48 hours
measure: Fecal Microbial Population
timeFrame: 48 hours
measure: Fecal Inulin
timeFrame: 48 hours
Secondary outcomes:
measure: Percent Primary Fecal Bile Acids
timeFrame: 48 hours
measure: Stool Characteristics - Stool Frequency in 4 Days
timeFrame: 4 days
measure: Stool Characteristics - Stool Form
timeFrame: 4 days
measure: Stool Characteristics - Ease of Passage
timeFrame: 4 days
Other outcomes:
measure: Energy
timeFrame: 24 hours
Locations:
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
Study officials:
affiliation: Indiana University
name: Huiping XU
role: PRINCIPAL_INVESTIGATOR
References: