Prebiotics and Diet to Reduce "Leaky" Gut in First Degree Relatives of Crohn's Disease Patients

NCT03950336 | Completed

• 1 other identifier: Pro00090125
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

Crohn's disease (CD) is a recurring inflammation of the intestines. The etiology is unknown; however evidence suggests that it could be a combination of gut microbes, environmental factors and genetics. CD has a strong genetic component, with up to 12% of patients having familial history. The Western diet is also thought to increase the risk of developing CD. In addition up to 20% of healthy first-degree relatives (FRD) of CD patients have increased small intestinal permeability ("leaky gut"). Previous studies have also shown that the Western diet can affect the intestinal immune response and normal intestinal barrier function, as well as alter the gut microbiota. We are interested in looking into whether beneficial dietary fibers (prebiotics) in combination with a diet low in n-6 polyunsaturated fatty acids (PUFAs) and high in n-3 PUFAs can protect against the development of CD. Prebiotics are carbohydrates that cannot be digested by human enzymes and instead feed the bacteria in the colon that can digest them. Prebiotics occur in different fruits and vegetables. They have been shown to improve health by positively changing the gut microbes and their metabolism. The prebiotic we will be using are β-fructans. β-fructans have been shown to reduce "leaky gut" and positively impact the intestinal immune system in experimental models and healthy humans. Diet has been shown to affect the gut microbes, intestinal inflammation development and the activity of prebiotics. We hypothesize that β-fructans in combination with a diet low in n-6 PUFAs / high in n-3 PUFAs (similar to a Mediterranean diet) can reduce intestinal permeability ("leaky gut") in FDR of CD patients, associated with beneficial changes in the gut microbes. Participants (FDR of CD patients; 40 total) will be randomized and receive either a 12 g/day dose of the prebiotic oligofructose-enriched inulin (Prebiotin), or placebo (maltodextrin), as well as a dietary intervention. In order to control the n-3 and n-6 PUFA intake, participants will receive nutritional counselling by a registered dietitian. The Mediterranean diet will have the low n-6 and high n-3 intake ("Low n-6 PUFA"). Participants in the control diet group will be advised to follow the Canada's Food Guide (CFG) recommendations. Thus, this placebo-controlled study will involve 2 intervention groups with 20 participants in each group: 1) Prebiotic + Low n-6 PUFA; 2) Placebo + CFG.

Conditions

Healthy First Degree Relatives of Crohn's Disease Patients

Keywords

intestinal permeability; Crohn's Disease (CD); oligofructose-enriched inulin; prebiotics; n-3 polyunsaturated fatty acids (n-3 PUFA); intestinal microbiota

Outcome Measures

Primary Outcomes (1)

• Change in small intestinal permeability over 6 weeks

  Lactulose mannitol ratio test will be used for in vivo assessment of intestinal permeability. Increased intestinal permeability is defined as a ratio of lactulose/mannitol 0.025 or more. Lactulose/mannitol ratio \< 0.025 is considered as normal.

  week 0 and week 6

Secondary Outcomes (3)

• Changes in serum/plasma markers for intestinal permeability

  weeks 0 and 6

• Changes in fecal microbiota and their metabolic activity

  weeks 0 and 6

• Participant compliance and tolerability

  weeks 0, 3 and 6

Study Arms (2)

Prebiotics + "Low n-6 PUFA Diet"

OTHER

A combination of beta-fructans (12g/day) and a diet with reduced intake of n-6 PUFAs and higher intake of n-3 PUFAs.

Dietary Supplement: Prebiotics; Other: Low n-6 PUFA Diet

Placebo + "Control Diet".

OTHER

A combination of maltodextrin (5g/day) and a control diet following the guidelines of Canada's Food Guide.

Dietary Supplement: Maltodextrin; Other: Control Diet

Interventions

Prebiotics DIETARY_SUPPLEMENT

Oligofructose-enriched inulin \[a combination of shorter chain oligofructose, Degree of Polymerisation (DP) 3 - 9 and longer chain inulin (DP ≥ 10), in a 50:50 ratio ± 10 %\] 12 g/day for 6 weeks

Also known as: Prebiotin

Prebiotics + "Low n-6 PUFA Diet"

Low n-6 PUFA Diet OTHER

The Mediterranean diet pattern (MDP) with increased n-3 PUFA, saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA) and reduced n-6 PUFAs food intake will be adopted as suitable Low n-6 PUFA diet.

Also known as: Mediterranean - based Diet

Prebiotics + "Low n-6 PUFA Diet"

Maltodextrin DIETARY_SUPPLEMENT

Maltodextrin consists of D-glucose units connected in chains of variable length (DP 3-17). The glucose units are primarily linked with α(1→4) glycosidic bonds. Maltodextrin is easily hydrolyzed by the intestinal enzymes and thus does not have an effect on colonic microbiota. Maltodextrin (5 g/days for 6 weeks) will be used as a placebo for the prebiotic treatment

Placebo + "Control Diet".

Control Diet OTHER

Participants who will not be assigned to "Low n-6 PUFA diet" will be advised to follow the Canada's Food Guide recommendations ("Control diet"). As Canada's Food Guide Diet is also designed with the aim to support healthy eating and prevention of metabolic and chronic disorders, this diet may not be considered as a true comparator for the Low n-6 PUFA diet intervention.

Also known as: Canada's Food Guide-based Diet

Placebo + "Control Diet".

Eligibility Criteria

• Age: 15 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Males and females aged 15 - 50;
• First degree relative (parent, sibling, child) of patient diagnosed with Crohn's disease;
• Agree not to use any dietary supplements, herbal treatments, probiotics, prebiotics or dietary therapies within 1 week of starting the trial and during the study;
• Willingness to keep current physical activity during study period;
• Ability to give valid informed consent
• For females of childbearing potential and sexually active, a negative pregnancy test at screening, baseline and end-of-study, and accord to use appropriate birth control method (hormonal contraceptives, intrauterine devices, vasectomy/tubal ligation, barrier methods (condom or diaphragm), double-barrier methods or abstinence) during study period.

You may not qualify if:

• Use of probiotic and prebiotic supplements, fish oil or NSAIDS, prescribed or over the counter in the last 1 week;
• Use of antibiotics in the last 2 months;
• Celiac disease (allergic reaction to wheat products), gluten intolerance/sensitivity;
• Diabetes or uncontrolled / unstable blood glucose levels;
• Having history or evidence of significant gastrointestinal dysfunction and Irritable Bowel Syndrome (IBS);
• Having an active gastrointestinal infection (confirmed by stool pathogen culture test and Clostridioides difficile test)
• Having history or evidence of blood and bleeding disorder;
• Having uncontrolled or unstable blood pressure;
• Having a significant chronic disorder such as immune disorders, organ transplant, severe cardiac disease, renal failure, severe pulmonary disease, severe psychiatric disorder;
• Alcohol or drug abuse;
• Pregnant or lactating;
• Not able to consent to the study.

Sponsors & Collaborators

• University of Alberta: lead

Study Sites (1)

University of Alberta

Edmonton, Alberta, T6G 2E1, Canada

Location

MeSH Terms

Conditions

Crohn Disease

Interventions

Prebiotics; maltodextrin

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Dietary Fiber; Dietary Carbohydrates; Carbohydrates; Polysaccharides, Bacterial; Polysaccharides; Food; Diet, Food, and Nutrition; Physiological Phenomena; Dietary Supplements; Food and Beverages

Study Officials

• Levinus Dieleman, MD, PhD

  University of Alberta

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Single-blind placebo controlled
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: placebo-controlled parallel study with two simultaneous interventions

Study Record Dates

• First Submitted: May 13, 2019
• First Posted: May 15, 2019
• Study Start: February 4, 2020
• Primary Completion: January 8, 2024
• Study Completion: May 17, 2024
• Last Updated: May 20, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)