Effect of Bile Acid Sequestration on Postprandial GLP-1 Secretion, Glucose Homeostasis and Gut Microbiota

NCT ID: NCT02061124

Last Updated: 2015-11-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-02-28

Study Completion Date

2015-10-31

Brief Summary

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Accumulating evidence suggests that bile acids and bacteria in our intestines may constitute essential components in the complex mechanisms regulating gut hormone secretion and glucose homeostasis. At the same time, bile acids and gut bacteria are interdependent. Thus, it is likely that modification of the enterohepatic circulation of bile acids can lead to changes in gut hormone secretion or gut bacteria composition and consequently affect glucose homeostasis.

The current study is a human interventional study with 7-day ingestion of a bile acid sequestrant or placebo, preceded and followed by meal tests and faecal sampling. The aim is to examine how (and if) bile acid sequestration can influence postprandial glucagon-like peptide-1 (GLP-1) secretion, gut microbiota and glucose homeostasis in patients with type 2 diabetes and healthy individuals. As a tool to sequester bile acids we will use sevelamer, a phosphate binding resin used in the treatment of hyperphosphataemia in adult patients with chronic kidney disease. Surprisingly, sevelamer was recently shown to improve glycaemic control in patients with chronic kidney disease and type 2 diabetes.

The investigators hypothesize that higher luminal concentrations of bile acids in the distal gut will elicit changes in the postprandial gut hormone secretion and gut bacteria composition. The current study will help to clarify this hypothesis and improve our general understanding of the association between bile acid circulation and signalling, gut hormone secretion, gut bacteria and glucose metabolism.

Detailed Description

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Conditions

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Type 2 Diabetes

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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T2DM, sevelamer

Patients with type 2 diabetes treated with sevelamer

Group Type ACTIVE_COMPARATOR

Sevelamer 1600 mg TID for 7 days

Intervention Type DRUG

T2DM, placebo

Patients with type 2 diabetes treated with placebo

Group Type PLACEBO_COMPARATOR

Placebo 1600 mg TID for 7 days

Intervention Type DRUG

Healthy subjects, sevelamer

Healthy subjects treated with sevelamer

Group Type ACTIVE_COMPARATOR

Sevelamer 1600 mg TID for 7 days

Intervention Type DRUG

Healthy subjects, placebo

Healthy subjects treated with placebo

Group Type PLACEBO_COMPARATOR

Placebo 1600 mg TID for 7 days

Intervention Type DRUG

Interventions

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Sevelamer 1600 mg TID for 7 days

Intervention Type DRUG

Placebo 1600 mg TID for 7 days

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

Both groups

* Caucasian ethnicity
* Normal haemoglobin
* Age above 35 years and below 80 years
* Informed and written consent
* BMI \> 23 kg/m2 and \<35 kg/m2

Patients with type 2 diabetes

* Type 2 diabetes for at least 3 months
* Diagnosed according to the criteria of the World Health Organization (WHO)

Healthy Subjects

* Normal fasting plasma glucose (FPG) \<6.5 mM and
* Normal glycated haemoglobin (HbA1c) \<6.0 %

Exclusion Criteria

Both groups

* Liver disease (alanine aminotransferase (ALAT) and/or serum aspartate aminotransferase (ASAT) \>2 times normal values) or history of hepatobiliary disorder
* Gastrointestinal disease, previous intestinal resection, cholecystectomy or any major intra-abdominal surgery
* Hypo- or hyperphosphataemia
* Nephropathy (serum creatinine \>150 µM and/or albuminuria
* Treatment with medicine that cannot be paused for 12 hours
* Intake of antibiotics six months prior to study
* Hypo- or hypercalcaemia
* Hypo- and hyperthyroidism
* Treatment with oral anticoagulants
* Active or recent malignant disease
* Any treatment or condition requiring acute or sub-acute medical or surgical intervention
* Lack of effective birth control in premenopausal women
* Positive pregnancy test on study days in premenopausal women
* Tobacco smoking
* Any condition considered incompatible with participation by the investigators

Patients with type 2 diabetes

* Treatment with insulin
* Treatment with incretin-based therapy

Healthy Subjects

* Diabetes or
* prediabetes (fasting plasma glucose levels \>6.5 mM or HbA1c \>6.0%)
* First-degree relatives with diabetes
Minimum Eligible Age

35 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Sanofi

INDUSTRY

Sponsor Role collaborator

University Hospital, Gentofte, Copenhagen

OTHER

Sponsor Role lead

Responsible Party

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Andreas Brønden

MD

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Diabetes Research Division, Gentofte Hospital, Copenhagen

Hellerup, , Denmark

Site Status

Countries

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Denmark

Other Identifiers

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H-2-2013-148

Identifier Type: -

Identifier Source: org_study_id