Effect of Bile Acids on GLP-1 Secretion

NCT01666223 | Completed DMC

• 1 other identifier: H-1-2012-049
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Type 2 Diabetes; Obesity

Keywords

Type 2 diabetes; GLP-1; Bile acid; TGR-5

Outcome Measures

Primary Outcomes (1)

• Change in GLP-1

  At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes

Secondary Outcomes (14)

• Change in insulin

  At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes

• Change in C-peptide

  At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes

• Change in glucagon

  At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes

• Change in glucagon-like-peptide 2 (GLP-2)

  At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes

• Change in glucose-dependent insulinotropic polypeptide (GIP)

  At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes

Study Arms (4)

Colesevelam

EXPERIMENTAL

Drug: Colesevelam

Chenodeoxycholic acid

EXPERIMENTAL

Drug: Chenodeoxycholic Acid

Colesevelam + chenodeoxycholic acid

EXPERIMENTAL

Drug: Colesevelam 3750 mg + chenodeoxycholic acid 1250 mg

Placebo

EXPERIMENTAL

Other: saline

Interventions

Colesevelam DRUG

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

Colesevelam

Chenodeoxycholic Acid DRUG

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

Chenodeoxycholic acid

saline OTHER

100 ml saline

Placebo

Colesevelam 3750 mg + chenodeoxycholic acid 1250 mg DRUG

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

Colesevelam + chenodeoxycholic acid

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

• 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
• danish caucasian ethnicity
• normal haemoglobin
• HbA1c \< 6,0 (American Diabetes Association guidelines)
• informed consent
• liver disease(ALT and AST \> upper reference limit)
• gastrointestinal disease

Sponsors & Collaborators

• University Hospital, Gentofte, Copenhagen: lead

Study Sites (1)

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

Hellerup, Copenhagen, Denmark

Location

Related Publications (4)

• 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.

  PMID: 12419312 BACKGROUND

• 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.

  PMID: 8406158 BACKGROUND

• 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.

  PMID: 15721318 BACKGROUND

• 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.

  PMID: 21521075 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Obesity

Interventions

Colesevelam Hydrochloride; Chenodeoxycholic Acid; Sodium Chloride

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Allylamine; Amines; Organic Chemicals; Allyl Compounds; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Deoxycholic Acid; Cholic Acids; Bile Acids and Salts; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Cholanes; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Morten Hansen, MD

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD Student

Study Record Dates

• First Submitted: July 11, 2012
• First Posted: August 16, 2012
• Study Start: November 1, 2012
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: December 24, 2013

Record last verified: 2013-12

Locations

DK (1)