Effect of Bile Acids on GLP-1 Secretion

NCT ID: NCT01666223

Last Updated: 2013-12-24

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

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-11-30

Study Completion Date

2013-06-30

Brief Summary

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The purpose of this study is to describe the physiological, pathophysiological and potentially therapeutic implications of bile-induced glucagon-like peptide-1 (GLP-1) secretion in human glucose homeostasis.

Detailed Description

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The investigators hypothesize that even modest increments in endogenous GLP-1 secretion will elicit important antidiabetic effects of GLP-1. To evaluate whether bile acids have such effects, the investigators plan to perform intraduodenal infusion of two different bile acids and placebo.

Conditions

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Type 2 Diabetes Obesity

Keywords

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Type 2 diabetes GLP-1 Bile acid TGR-5

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Colesevelam

Group Type EXPERIMENTAL

Colesevelam

Intervention Type DRUG

Colesevelam 3750 mg dissolved in 100 ml saline, administered in a feeding tube at time = 0.

Chenodeoxycholic acid

Group Type EXPERIMENTAL

Chenodeoxycholic Acid

Intervention Type DRUG

1.250 mg dissolved in 100 ml saline, administered in a feeding tube at time = 0.

Colesevelam + chenodeoxycholic acid

Group Type EXPERIMENTAL

Colesevelam 3750 mg + chenodeoxycholic acid 1250 mg

Intervention Type DRUG

Colesevelam and chenodeoxycholic acid dissolved in 100 ml saline, administered in a duodenal tube at time = 0.

Placebo

Group Type EXPERIMENTAL

saline

Intervention Type OTHER

100 ml saline

Interventions

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Colesevelam

Colesevelam 3750 mg dissolved in 100 ml saline, administered in a feeding tube at time = 0.

Intervention Type DRUG

Chenodeoxycholic Acid

1.250 mg dissolved in 100 ml saline, administered in a feeding tube at time = 0.

Intervention Type DRUG

saline

100 ml saline

Intervention Type OTHER

Colesevelam 3750 mg + chenodeoxycholic acid 1250 mg

Colesevelam and chenodeoxycholic acid dissolved in 100 ml saline, administered in a duodenal tube at time = 0.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* danish caucasian ethnicity
* normal haemoglobin
* BMI \> 25 kg/m2
* HbA1c \< 9%
* informed consent


* danish caucasian ethnicity
* normal haemoglobin
* HbA1c \< 6,0 (American Diabetes Association guidelines)
* informed consent

Exclusion Criteria

* liver disease(ALT and AST \> upper reference limit)
* gastrointestinal disease
* liver and biliary tract disease
* nephropathy (serum creatinine \> 150 μM, and/or albuminuria)
* treatment with insulin, glp-1 analogues and/ or DPP-4 inhibitors
* treatment with medicine that can not be paused for 12 hours
* previous abdominal surgery eg. cholecystectomy
* BMI \< 18,5 kg/m2 or \> 35 kg/m2

Healthy Volunteers


* liver disease(ALT and AST \> upper reference limit)
* gastrointestinal disease
* liver and biliary tract disease
* nephropathy (serum creatinine \> 150 μM, and/or albuminuria)
* treatment with medicine that can not be paused for 12 hours
* previous abdominal surgery eg. cholecystectomy
* BMI \< 18,5 kg/m2 or \> 35 kg/m2
* first degree relatives diagnosed with diabetes
* previously diagnosed with diabetes, or treated with antidiabetic agents
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University Hospital, Gentofte, Copenhagen

OTHER

Sponsor Role lead

Responsible Party

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Morten Hansen

MD, PhD Student

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Morten Hansen, MD

Role: PRINCIPAL_INVESTIGATOR

Diabetes Research Division, Department of Internal Medicine, Gentofte Hospital, University of Copenhagen

Locations

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Diabetes Research Division, Department of Internal Medicine, Gentofte Hospital, University of Copenhagen

Hellerup, Copenhagen, Denmark

Site Status

Countries

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Denmark

References

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Maruyama T, Miyamoto Y, Nakamura T, Tamai Y, Okada H, Sugiyama E, Nakamura T, Itadani H, Tanaka K. Identification of membrane-type receptor for bile acids (M-BAR). Biochem Biophys Res Commun. 2002 Nov 15;298(5):714-9. doi: 10.1016/s0006-291x(02)02550-0.

Reference Type BACKGROUND
PMID: 12419312 (View on PubMed)

Adrian TE, Ballantyne GH, Longo WE, Bilchik AJ, Graham S, Basson MD, Tierney RP, Modlin IM. Deoxycholate is an important releaser of peptide YY and enteroglucagon from the human colon. Gut. 1993 Sep;34(9):1219-24. doi: 10.1136/gut.34.9.1219.

Reference Type BACKGROUND
PMID: 8406158 (View on PubMed)

Katsuma S, Hirasawa A, Tsujimoto G. Bile acids promote glucagon-like peptide-1 secretion through TGR5 in a murine enteroendocrine cell line STC-1. Biochem Biophys Res Commun. 2005 Apr 1;329(1):386-90. doi: 10.1016/j.bbrc.2005.01.139.

Reference Type BACKGROUND
PMID: 15721318 (View on PubMed)

Rafferty EP, Wylie AR, Hand KH, Elliott CE, Grieve DJ, Green BD. Investigating the effects of physiological bile acids on GLP-1 secretion and glucose tolerance in normal and GLP-1R(-/-) mice. Biol Chem. 2011 Apr;392(6):539-46. doi: 10.1515/BC.2011.050. Epub 2011 Apr 27.

Reference Type BACKGROUND
PMID: 21521075 (View on PubMed)

Other Identifiers

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H-1-2012-049

Identifier Type: -

Identifier Source: org_study_id