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

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ClinicalTrials.gov Identifier: NCT03950336
Recruitment Status : Not yet recruiting
First Posted : May 15, 2019
Last Update Posted : May 17, 2019
Sponsor:
Information provided by (Responsible Party):
University of Alberta

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 alone or in combination with a diet low in n-6 PUFAs / high in n-3 PUFAs (similar to a Mediterranean diet) can reduce "leaky gut" in FDR of CD patients, associated with beneficial changes in the gut microbes.

Participants (FDR of CD patients; 32 total) with confirmed "leaky gut" 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 4 intervention groups with 8 participants in each group: 1) Prebiotic + Low n-6 PUFA; 2) Prebiotic + CFG; 3) Placebo + Low n-6 PUFA; 4) Placebo + CFG.


Condition or disease Intervention/treatment Phase
Healthy First Degree Relatives of Crohn's Disease Patients Dietary Supplement: Prebiotics Other: Low n-6 PUFA Diet Dietary Supplement: Maltodextrin Other: Control Diet Not Applicable

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 32 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: placebo-controlled parallel study with two simultaneous interventions
Masking: Double (Participant, Investigator)
Masking Description: Double-blind placebo controlled
Primary Purpose: Other
Official Title: Influence of Prebiotics on Intestinal Permeability in First Degree Relatives of Crohn's Patients
Estimated Study Start Date : July 2019
Estimated Primary Completion Date : September 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Crohn's Disease

Arm Intervention/treatment
Prebiotics + "Low n-6 PUFA Diet"
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
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 12 weeks
Other Name: Prebiotin

Other: Low n-6 PUFA Diet
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.
Other Name: Mediterranean - based Diet

Prebiotics + "Control Diet"
A combination of beta-fructans (12g/day) and a control diet following the guidelines of Canada's Food Guide.
Dietary Supplement: Prebiotics
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 12 weeks
Other Name: Prebiotin

Other: Control Diet
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.
Other Name: Canada's Food Guide-based Diet

Placebo + "Low n-6 PUFA Diet"
A combination of maltodextrin (12g/day) and a diet with reduced intake of n-6 PUFAs and higher intake of n-3 PUFAs.
Other: Low n-6 PUFA Diet
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.
Other Name: Mediterranean - based Diet

Dietary Supplement: Maltodextrin
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 (12 g/days for 12 weeks) will be used as a placebo for the prebiotic treatment

Placebo + "Control Diet".
A combination of maltodextrin (12g/day) and a control diet following the guidelines of Canada's Food Guide.
Dietary Supplement: Maltodextrin
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 (12 g/days for 12 weeks) will be used as a placebo for the prebiotic treatment

Other: Control Diet
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.
Other Name: Canada's Food Guide-based Diet




Primary Outcome Measures :
  1. Change in small intestinal permeability over 12 weeks [ Time Frame: week 0 and week 12 ]
    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.


Secondary Outcome Measures :
  1. Changes in serum/plasma markers for intestinal permeability [ Time Frame: weeks 0, 6 and 12 ]
    Zonulin, glucagon like protein 2 (GLP-2) and lipopolysaccharides (LPS) are chosen as markers for intestinal permeability

  2. Changes in fecal microbiota and their metabolic activity [ Time Frame: weeks 0 and 12 ]
    Assessment by 16S ribosomal DNA (rDNA) microbial sequencing; short-chain fatty acids and bile acids measurement



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Ages Eligible for Study:   15 Years to 50 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Males and females aged 15 - 50
  • First degree relative (parent, sibling, child) of patient diagnosed with Crohn's disease
  • Having increased small intestinal permeability (defined as a ratio of lactulose/mannitol 0.025 or greater)
  • Agree not to use any dietary supplements, herbal treatments, probiotics, prebiotics or dietary therapies within 3 weeks of starting the trial or during the study
  • Ability to give valid informed consent
  • For females of child bearing potential, a negative pregnancy test.

Exclusion Criteria:

  • Use of probiotic and prebiotic supplements, fish oil or non-steroidal anti-inflammatory drugs (NSAIDS), prescribed or over the counter
  • Use of antibiotics in the last 2 months
  • Celiac disease (allergic reaction to wheat products)
  • Diabetes
  • 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 Clostridoides difficile test)
  • Having a significant chronic disorders as severe cardiac disease, renal failure, severe pulmonary disease, severe psychiatric disorder;
  • Pregnant or lactating
  • Not able to consent to the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03950336


Contacts
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Contact: Rosica Valcheva, PhD 7804920019 valcheva@ualberta.ca
Contact: Nilanjani Premraj, MSc premraj@ualberta.ca

Sponsors and Collaborators
University of Alberta
Investigators
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Principal Investigator: Levinus Dieleman, MD, PhD University of Alberta

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Responsible Party: University of Alberta
ClinicalTrials.gov Identifier: NCT03950336     History of Changes
Other Study ID Numbers: Pro00090125
First Posted: May 15, 2019    Key Record Dates
Last Update Posted: May 17, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: No IPD will be shared outside the study team.

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

Keywords provided by University of Alberta:
intestinal permeability
Crohn's Disease (CD)
oligofructose-enriched inulin
prebiotics
n-3 polyunsaturated fatty acids (n-3 PUFA)
intestinal microbiota

Additional relevant MeSH terms:
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Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases