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Milk-derived Gangliosides for Inflammatory Bowel Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02139709
Recruitment Status : Unknown
Verified June 2015 by Thomas Clandinin, University of Alberta.
Recruitment status was:  Active, not recruiting
First Posted : May 15, 2014
Last Update Posted : June 4, 2015
Sponsor:
Information provided by (Responsible Party):
Thomas Clandinin, University of Alberta

Brief Summary:

The overall objective of this study is to demonstrate how dietary ganglioside may protect the gut attenuate inflammatory signals in the intestinal mucosa.

Gangliosides are dietary fats found in milk and are important constituents of intestinal cells. Our previous studies have shown that inflamed intestinal mucosal cells have reduced ganglioside content compared to normal mucosal cells. Gangliosides are glycolipids found on the surface of the intestinal mucosa and in lipid rafts in enterocytes and lymphocytes. Gangliosides influence microbial attachment, cell division, differentiation, signaling and mucosal integrity. Preclinical studies show that provision of ganglioside in cell culture and in animal diets increase ganglioside content in mucosal cells and down regulates signals caused by pro-inflammatory stimuli. In subjects with active Crohn's disease, consumption of ganglioside remarkably improved the Crohn's Disease Activity Index. In healthy control subjects, dietary ganglioside improved intestinal permeability and decreased production of pro-inflammatory prostaglandin E2.

It is proposed that ganglioside degradation is elevated in the inflamed gut of IBD patients. Provision of ganglioside in the diet replaces ganglioside in the gut, consequently restoring proper structure and function to the diseased intestine and inducing disease remission. Insight into diet-based treatment would allow IBD patients to live healthy and happy lives. The main research objective is to characterize how ganglioside catabolism is associated with increased signaling from pro-inflammatory mediators and how reduction in ganglioside levels can be ameliorated by ganglioside supplementation during active inflammatory disease. This study will assess molecular mechanisms by which ganglioside alters gut permeability, inflammatory mediators and cell signaling.


Condition or disease Intervention/treatment Phase
Inflammatory Bowel Disease Dietary Supplement: Ganglioside Dietary Supplement: Placebo Phase 1

Detailed Description:

OBJECTIVES

Objective 1 will test if dietary ganglioside treatment improves intestinal integrity, permeability and systemic inflammation in patients with inflammatory bowel disease (IBD).

Objective 2 will study the bioavailability of dietary ganglioside

BACKGROUND & SCOPE

This is a pilot study being conducted in patients with mild-moderate IBD as assessed by Crohn's disease activity index or Mayo Score. Our studies indicate that some ganglioside species prevent proinflammatory stimuli and prevent disruption of integrity of tight junctions between enterocytes, normalizing transepithelial electrical resistance in inflamed cells. Feeding ganglioside to rats prevented lipopolysaccharide-stimulated decrease in cellular tight junction protein occludin. Low level of GD3 ganglioside in the intestinal mucosa is associated with degradation of tight junction proteins. Increasing the GD3 content of the intestinal mucosa thus reduces the degradation of tight junction proteins improving the integrity of the brush border and improving the deleterious changes occurring in intestinal permeability. Improving intestinal integrity in subjects with IBD is important to manage diarrhea, infection, penetration of allergens, and malnutrition. Research in progress from our group demonstrates that dietary ganglioside decreased level of pro-inflammatory prostaglandin E2 in healthy human subjects and those with Crohn's disease. Also, daily consumption of ganglioside was very effective in improving the Crohn's disease activity index by an average of 43% over an eight-week study period.

METHODS & PROCEDURE

Subject Recruitment Healthy control subjects and patients with Crohn's disease and ulcerative colitis will be recruited in Edmonton from the University of Alberta Hospital gastroenterology clinic. Male and (non-pregnant) female adults (> 17 year of age) are eligible for study. Pre-operative IBD patients with mild to moderate disease including those with rectosigmoiditis, left-sided colitis, concurrent small bowel disease, and Crohn's will be recruited. Diagnosis will be based on established radiologic, endoscopic, and histologic criteria.

Dietary Treatment with Ganglioside Ganglioside will be provided in the form of a ganglioside-enriched milk fat globule membrane. This buttermilk supernatant contains protein, lactose, and 0.4% ganglioside (75% GD3, 25% GM3). Normal preparation of butter yields buttermilk. The ganglioside fraction used in this study has been centrifuged and filtered again to remove the casein and whey protein. Participants will be randomized to consume either 1.0 g of ganglioside or placebo daily for eight weeks in addition to their standard drug treatment. The placebo milk fraction does not contain ganglioside, and is equal in protein and lactose content to the ganglioside fraction.

Subject Involvement Participants will have blood drawn at baseline and week 2, 4, 6 and 8 of supplementation study. Subject disease Activity Index or Mayo Score will be obtained at weeks 0 and 8. Participants will undergo non-invasive intestinal permeability testing at study weeks 0 and 8.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Milk-derived Gangliosides as Novel Anti-inflammatory Therapy for Inflammatory Bowel Disease
Study Start Date : January 2007
Estimated Primary Completion Date : January 2016
Estimated Study Completion Date : June 2016

Arm Intervention/treatment
Experimental: Ganglioside
1.0 gram ZETA dairy lipid powder (Fonterra NZ)
Dietary Supplement: Ganglioside
Placebo Comparator: Placebo
1.0 gram milk fat fraction void of ganglioside
Dietary Supplement: Placebo



Primary Outcome Measures :
  1. Percent change in intestinal permeability [ Time Frame: 8 weeks ]
    Measurement of the percent change in excretion of urinary lactulose/mannitol between study conclusion (day 56) and initiation (day 0).


Secondary Outcome Measures :
  1. Change in inflammatory markers [ Time Frame: 8 weeks ]
    Change in plasma levels of leukotriene B4, prostaglandin E2 and tumor necrosis factor alpha (pg/mL) over course of study.


Other Outcome Measures:
  1. Percent Change in Ganglioside Bioavailability [ Time Frame: 8 weeks ]
    Measurement of percent change in plasma ganglioside concentration over course of study.



Information from the National Library of Medicine

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Ages Eligible for Study:   17 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • patients with mild - moderate Inflammatory Bowel Disease defined by Crohn's disease activity index or Mayo Score
  • IBD patients and healthy subjects > 17 years of age

Exclusion Criteria:

  • use of corticosteroids, immunosuppressants, antibiotics, infliximab
  • pregnant
  • inadequate liver or renal function
  • cancer
  • active infectious disease
  • history of alcohol/drug abuse
  • serious complications of Crohn's disease or ulcerative colitis
  • bowel obstruction
  • other serious medical conditions

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): NCT02139709


Locations
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Canada, Alberta
Zeidler Ledcor gastroenterology clinic
Edmonton, Alberta, Canada, T6G 2B7
Sponsors and Collaborators
University of Alberta
Investigators
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Principal Investigator: Michael T Clandinin, PhD University of Alberta
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Thomas Clandinin, Professor Emeritus, University of Alberta
ClinicalTrials.gov Identifier: NCT02139709    
Other Study ID Numbers: Pro00001371
First Posted: May 15, 2014    Key Record Dates
Last Update Posted: June 4, 2015
Last Verified: June 2015
Additional relevant MeSH terms:
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Intestinal Diseases
Inflammatory Bowel Diseases
Gastrointestinal Diseases
Digestive System Diseases
Gastroenteritis