Inflammatory Bowel DiseasePhase 1NCT02139709
Milk-derived Gangliosides for Inflammatory Bowel Disease
A Phase 1 study testing Ganglioside in people with Inflammatory Bowel Disease, run by University of Alberta at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 17 years and olderHealthy volunteers can take part
- Conditions the study is for
- Inflammatory Bowel Disease
- What is being tested?
- Ganglioside
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteCanada
- Study dates
- Jan 2007to Aug 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 17 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- use of corticosteroids, immunosuppressants, antibiotics, infliximab
- pregnant
- inadequate liver or renal function
- cancer
- active infectious disease
- history of alcohol/drug abuse
Show all 9Show fewer
- serious complications of Crohn's disease or ulcerative colitis
- bowel obstruction
- other serious medical conditions
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Milk-derived Gangliosides as Novel Anti-inflammatory Therapy for Inflammatory Bowel Disease
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.
Read the 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.
- Conditions
- Inflammatory Bowel Disease
- Being tested
- Ganglioside, Placebo
- Medical subject headings
- Inflammatory Bowel Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GangliosideDietary supplement
PlaceboDietary supplement
| Study group | Role | What they receive |
|---|---|---|
| Ganglioside | Experimental | 1.0 gram ZETA dairy lipid powder (Fonterra NZ) Receives: Dietary Supplement: Ganglioside |
| Placebo | Placebo comparator | 1.0 gram milk fat fraction void of ganglioside Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 8 weeks
Secondary outcomes (1)
Change in inflammatory markers
Change in plasma levels of leukotriene B4, prostaglandin E2 and tumor necrosis factor alpha (pg/mL) over course of study.
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2014 (estimated)
- Study startJan 2007
- Primary completionAug 2015
- Study completionAug 2015
Why it stopped: REB Approval expired.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Inflammatory Bowel DiseaseStudies of the same condition, open and under way.
- More trials run by University of AlbertaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alberta
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Michael T Clandinin, PhD, Principal investigator, University of Alberta
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02139709
- Sponsor's protocol ID
- Pro00001371
- Status last verified
- Jul 2022
- First submitted
- 8 May 2014
- Last updated
- 18 Jul 2022
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 26673692
Study at a glance
From the registry record, last updated by the sponsor on 18 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Milk-derived Gangliosides as Novel Anti-inflammatory Therapy for Inflammatory Bowel Disease
- ClinicalTrials.gov ID
- NCT02139709
- Acronym / sponsor ID
- Pro00001371
- Conditions
- Inflammatory Bowel Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: REB Approval expired.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of AlbertaUniversity, hospital or other
- Study start
- Jan 2007
- Primary completion
- Aug 2015 (actual)
- Study completion
- Aug 2015 (actual)
- First posted
- 15 May 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ganglioside | Experimental | Dietary Supplement: Ganglioside1.0 gram ZETA dairy lipid powder (Fonterra NZ) |
| Placebo | Placebo comparator | Dietary Supplement: Placebo1.0 gram milk fat fraction void of ganglioside |
Who may qualify
- Ages
- 17 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (9 listed)
- use of corticosteroids, immunosuppressants, antibiotics, infliximab
- pregnant
- inadequate liver or renal function
- cancer
- active infectious disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ganglioside | Dietary supplement | Ganglioside |
| Placebo | Dietary supplement | Placebo |
Primary outcome
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).
1 secondary outcome
Change in inflammatory markers
Time frame: 8 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2022.
- Derived from this study: PubMed 26673692Miklavcic 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael T Clandinin, PhD principal investigator
University of Alberta
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ganglioside in people with Inflammatory Bowel Disease, run by University of Alberta at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 18 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent change in intestinal permeability (time frame: 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02139709, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jul 2022; AzTrials last refreshed its copy on 6 Nov 2026.