The Effects of Soluble Corn Fiber on Gastrointestinal Tolerance and Fecal Microbiome in Healthy Children

A Randomized, Controlled, Crossover Study to Assess the Effects of Soluble Corn Fiber on Gastrointestinal Tolerance and Fecal Microbiome in Healthy Children

The purpose of this study is to compare the effects of PROMITOR® Soluble Corn Fiber versus inulin on GI symptoms (tolerance), stool consistency (laxation) and fecal microbiome at levels that could contribute to closing the fiber gap. The dose response effects of PROMITOR® Soluble Corn Fiber in healthy children will also be compared.

After initial site visits and randomization children were given a packet of powdered fiber to be mixed into a beverage daily. There were four test arms, described elsewhere. Each study arm lasted 10 days with an 18 day washout in between study periods.

Inclusion Criteria:

1. Male or female, 3-9 years of age, inclusive at Visit 1 (Day -7)
2. Potty trained
3. Bowel movement at least every other day.
4. Regularly consumes breakfast (at least 5 times/week) and agrees to consume breakfast every day during each test period.
5. Willing to maintain physical activity and exercise patterns, body weight, and habitual diet throughout the trial.
6. Willing to refrain from exclusionary medications, supplements, and products throughout the study.
7. No health conditions that would prevent him/her from fulfilling the study requirements as judged by the Clinical Investigator on the basis of medical history.
8. Caregiver understands the study procedures and signs forms providing informed consent to participate in the study and authorizes the release of relevant protected health information to the Clinical Investigator and subject provides informed assent.

Exclusion criteria

1. Regular (>2/week) moderate to severe GI symptoms (as reported by subject and/or caregiver at Visit 1, Day -7). Mild and infrequent (≤ 2/week) GI symptoms are allowed.

2. Subject will be away from caregiver for more than 1 day during the 3-day baseline period (Days -3, -2, and -1) and >48 consecutive hours during the 10 days of study product consumption during each test period. Goal is to recruit subjects who will be with their caregiver all or most of the time to minimize missing data.

3. Clinically important GI conditions that would potentially interfere with the evaluation of the study product [e.g., inflammatory bowel disease, irritable bowel syndrome, gastric reflux, indigestion, dyspepsia, Crohn's disease, celiac disease, gastroparesis, and clinically significant lactose and gluten intolerance or other food or ingredient allergies which includes allergies to milk, eggs, peanuts, tree nuts, wheat and soy (Appendix 9)].

4. Recent (within 2 weeks of Visit 1; Day -7) history of an episode of acute GI illness such as nausea/vomiting or diarrhea (defined as ≥ 3 loose or liquid stools/day).

5. Caregiver-reported history (within 4 weeks of Visit 1; Day -7) of any constipation (<3 bowel movement/week) and diarrhea (≥3 of more loose stools/day) at the discretion of the Clinical Investigator.

6. Uncontrolled and/or clinically important pulmonary (including uncontrolled asthma), cardiac (including, but not limited to, atherosclerotic disease, history of myocardial infarction, peripheral arterial disease, stroke), hepatic, renal, endocrine (including Type 1 and Type 2 diabetes mellitus), hematologic, immunologic, neurologic, neurological (e.g., depression and/or anxiety disorders) or biliary disorders. Conditions which are well-controlled or resolved will be assessed by the Clinical Investigator on a case-by-case basis.

7. Uncontrolled hypertension determined by the blood pressure measured at Visit 1 (Day -7) and defined as (https://www.emedicinehealth.com/pediatric\_vital\_signs/article\_em.htm):

   • Children 3-5 years old: Systolic blood pressure >107 mm Hg and diastolic blood pressure >71 mm Hg
   • Children 6-9 years old: Systolic blood pressure >110 mm Hg and diastolic blood pressure >73 mm Hg One re-test will be allowed on a separate day prior to Visit 2 (Day 0), for subjects whose blood pressure exceeds either of these cut points at Visit 1 (Day -7), in the judgment of the Clinical Investigator.

8. Extreme dietary habits as determined using the Diet Questionnaire (Appendix 2) and at the discretion of the Clinical Investigator.

9. History or presence of cancer in the prior 2 years, except for non-melanoma skin cancer.

10. Major trauma or any other surgical event within 3 months of Visit 1 (Day -7).

11. Signs or symptoms of an active infection of clinical relevance within 5 days of Visit 1 (Day -7). The visit may be rescheduled such that all signs and symptoms have resolved (at the discretion of the Clinical Investigator) at least 5 days prior to Visit 1 (Day -7).*

12. Weight loss or gain >4.5 kg in the 3 months prior to Visit 1 (Day -7).

13. Currently or planning to be on a weight loss regimen during the study.

14. Antibiotic use within 3 months of Visit 1 (Day -7).

15. Use of steroids within 1 month of Visit 1 (Day -7).

16. Chronic use (i.e., daily on a regular basis) of anti-inflammatory medications (e.g., NSAIDs) within 1 month of Visit 1 (Day -7).

17. Use of medications (over-the-counter or prescription) and/or dietary supplements, known to influence GI function, including but not limited to prebiotics or probiotics, laxatives, enemas, fiber supplements and/or suppositories, antacids, anti-diarrheal agents, and/or anti-spasmodic within 2 weeks of Visit 1 (Day -7). Standard multivitamin and mineral supplements are allowed. Clinic staff will check ingredient lists of supplements for presence of prebiotics or probiotics.

18. Use of allergy medications (prescription or over the counter) for >2 times/week within 2 weeks of Visit 1 (Day -7).

19. Exposure to any non-registered drug product within 4 weeks prior to Visit 1 (Day -7).

20. Has a condition the Clinical Investigator believes would interfere with his/her ability to provide informed consent, comply with the study protocol, which might confound the interpretation of the study results, or put the subject at undue risk.

    • If an infection occurs during the study period, test visits will be rescheduled until signs and symptoms have resolved (at the discretion of the Clinical Investigator) at least 5 days prior to study visits.

5.4.3 Excluded Products

• Antibiotics within 3 months of Visit 1 (Day -7) and throughout the study period.
• Steroids within 1 month of Visit 1 (Day -7) and throughout the study period.
• Chronic use (i.e., daily on a regular basis) of anti-inflammatory medications (e.g., NSAIDs) within 1 month of Visit 1 (Day -7) and throughout the study period.
• Medications (over-the-counter or prescription) and/or dietary supplements known to influence GI function, including but not limited to prebiotics or probiotics, laxatives, enemas, fiber supplements and/or suppositories, antacids, anti-diarrheal agents, and/or anti-spasmodic excluded within 2 weeks of Visit 1 (Day -7) and throughout the study period. Standard multivitamin and mineral supplements are allowed.
• Allergy medications of >2 times/week within 2 weeks of Visit 1 (Day -7). Consumption of any of these excluded products during the study period should be documented and subjects may be excluded from the Per Protocol population following a review of protocol deviations at the end of the intervention. Should a subject require any of these excluded products, the study staff should consult with the Clinical Investigator and/or designee to determine future action (e.g., early termination, extension of washout period, etc.)