Milk-derived Gangliosides for Inflammatory Bowel Disease

NCT02139709 | Withdrawn Phase 1

• 1 other identifier: Pro00001371
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Inflammatory Bowel Disease

Outcome Measures

Primary Outcomes (1)

• Percent change in intestinal permeability

  Measurement of the percent change in excretion of urinary lactulose/mannitol between study conclusion (day 56) and initiation (day 0).

  8 weeks

Secondary Outcomes (1)

• Change in inflammatory markers

  8 weeks

Other Outcomes (1)

• Percent Change in Ganglioside Bioavailability

  8 weeks

Study Arms (2)

Ganglioside

EXPERIMENTAL

1.0 gram ZETA dairy lipid powder (Fonterra NZ)

Dietary Supplement: Ganglioside

Placebo

PLACEBO COMPARATOR

1.0 gram milk fat fraction void of ganglioside

Dietary Supplement: Placebo

Interventions

Ganglioside DIETARY_SUPPLEMENT

Ganglioside

Placebo DIETARY_SUPPLEMENT

Placebo

Eligibility Criteria

• Age: 17 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Alberta: lead

Study Sites (1)

Zeidler Ledcor gastroenterology clinic

Edmonton, Alberta, T6G 2B7, Canada

Location

Related Publications (1)

• Miklavcic JJ, Shoemaker GK, Schnabl KL, Larsen BMK, Thomson ABR, Mazurak VC, Clandinin MT. Ganglioside Intake Increases Plasma Ganglioside Content in Human Participants. JPEN J Parenter Enteral Nutr. 2017 May;41(4):657-666. doi: 10.1177/0148607115620093. Epub 2015 Dec 16.

  PMID: 26673692 DERIVED

MeSH Terms

Conditions

Inflammatory Bowel Diseases

Interventions

Gangliosides

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Acidic Glycosphingolipids; Glycosphingolipids; Glycolipids; Glycoconjugates; Carbohydrates; Lipids; Sphingolipids; Membrane Lipids

Study Officials

• Michael T Clandinin, PhD

  University of Alberta

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2014
• First Posted: May 15, 2014
• Study Start: January 1, 2007
• Primary Completion: August 1, 2015
• Study Completion: August 1, 2015
• Last Updated: July 18, 2022

Record last verified: 2022-07

Locations

CA (1)