Efficacy and Safety of Ursodeoxycholic Acid (UDCA) Added to the DPP-4 Inhibitor in People With Type 2 Diabetes and Chronic Liver Diseases

Sponsor

Kanazawa University (Other)

Overall Status

Unknown status

CT.gov ID

NCT01337440

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Objectives
To test whether Ursodeoxycholic Acid (UDCA) increases Glucagon-like peptide-1 (GLP-1) response to nutrients and improves glycemic control in people with type 2 diabetes.
To test whether sitagliptin enhances UDCA-induced beneficial effect in GLP-1 levels and glycemic control.
To test safety of combination therapy of sitagliptin and UDCA in people with type 2 diabetes.
Clinical hypothesis.
UDCA increases GLP-1 response to nutrients via provoking bile acids excretion from the liver to the intestine/colon.
UDCA improves glycemic control in people with type 2 diabetes.
Sitagliptin enhances UDCA-induced response of GLP-1 to nutrients.
Sitagliptin has additive beneficial effects with UDCA in glycemic control in people with type 2 diabetes.
Combination therapy of sitagliptin and UDCA is safe and well-tolerated in people with type 2 diabetes.
The combination therapy may loose weight by unique mechanisms of each agent; GLP-1 inhibits appetite by acting on CNS and gastrointestinal motility, whereas UDCA-enhanced circulating primary bile acids increases energy expenditure through the pathway involving G protein-coupled bile acid receptor 1 (Gpbar1, or M-Bar, TGR-5) and subsequent activation of type 2 iodothyronine deiodinase (D2) in brown adipose and muscle tissues, as reported previously.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus Chronic Liver Disease	Drug: UDCA Drug: Sitagliptin	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

The Efficacy and Safety of Ursodeoxycholic Acid (UDCA) Added to the Dipeptidyl Peptidase-4 Inhibitor, Sitagliptin in People With Type 2 Diabetes and Chronic Liver Diseases

Study Start Date :

Apr 1, 2010

Anticipated Primary Completion Date :

Mar 1, 2013

Anticipated Study Completion Date :

Mar 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: UDCA pretreatment Ursodeoxycholic Acid (UDCA) for 12 weeks, then Sitagliptin add-on therapy for additional 12 weeks. UDCA dosage: dosing from 600 mg for initial 4 weeks. Then, if there is no adverse effect, UDCA is escalated to 900 mg, po, tid.	Drug: Sitagliptin UDCA for 12 weeks, then Sitagliptin add-on therapy for additional 12 weeks. UDCA dosage: dosing from 600 mg for initial 4 weeks. Then, if there is no adverse effect, UDCA is escalated to 900 mg, po, tid. Other Names: Sitagliptin sold under the trade name Januvia
Active Comparator: Sitagliptin pretreatment Sitagliptin: 50 mg, po, qd for 12 weeks, then UDCA add-on therapy for additional 12 weeks. UDCA dosage: dosing from 600 mg for initial 4 weeks. Then, if there is no adverse effect, UDCA is escalated to 900 mg, po, tid.	Drug: UDCA Sitagliptin: 50 mg, po, qd for 12 weeks, then UDCA add-on therapy for additional 12 weeks. UDCA dosage: dosing from 600 mg for initial 4 weeks. Then, if there is no adverse effect, UDCA is escalated to 900 mg, po, tid. Other Names: Ursodeoxycholic acid (UDCA) goes by the trade names Urso.

Arm

Intervention/Treatment

Active Comparator: UDCA pretreatment

Ursodeoxycholic Acid (UDCA) for 12 weeks, then Sitagliptin add-on therapy for additional 12 weeks. UDCA dosage: dosing from 600 mg for initial 4 weeks. Then, if there is no adverse effect, UDCA is escalated to 900 mg, po, tid.

Drug: Sitagliptin

UDCA for 12 weeks, then Sitagliptin add-on therapy for additional 12 weeks. UDCA dosage: dosing from 600 mg for initial 4 weeks. Then, if there is no adverse effect, UDCA is escalated to 900 mg, po, tid.

Other Names:

Sitagliptin sold under the trade name Januvia

Active Comparator: Sitagliptin pretreatment

Sitagliptin: 50 mg, po, qd for 12 weeks, then UDCA add-on therapy for additional 12 weeks. UDCA dosage: dosing from 600 mg for initial 4 weeks. Then, if there is no adverse effect, UDCA is escalated to 900 mg, po, tid.

Drug: UDCA

Other Names:

Ursodeoxycholic acid (UDCA) goes by the trade names Urso.

Outcome Measures

Primary Outcome Measures

the difference of haemoglobin A1c (HbA1c) and glycoalbumin (GA) [6 months]
the difference of haemoglobin A1c (HbA1c) and glycoalbumin (GA) treating by Ursodeoxycholic Acid (UDCA)or sitagliptin monotherapy, and combination therapy of both two drugs for 3 monthes.

Secondary Outcome Measures

Change from Baseline in Glucagon-like peptide-1 (GLP-1) response to lipid meal test (fat 55%) [6 months]
Change from Baseline in energy expenditure [6months]
Change from Baseline in fasting plasma glucose level [6months]
change from baseline in autonomic nerve function [6 months]
This is performed by power-spectrum analyses of heart rate variability

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Type 2 diabetes
HbA1c >=6.5% during 8 weeks prior to the study
Treated with none or single oral hypoglycemic agent(OHA: sulfonyl ureas, biguanides, or thiazolidinediones) over 12 weeks prior to the study

Exclusion Criteria:

Non-Type 2 diabetes
Medical history and/or complication of diabetic ketoacidosis
Medical history and/or complication of severe hypoglycemia
Insulin treatment within 16 weeks prior to the study
Treatment with alpha-glucosidase inhibitors or sitagliptin within 12 weeks prior to the study
Treatment with glucocorticoid
Unstable glycemic control
Hypersensitivity to or contraindication of sitagliptin and voglibose
Aspartate transaminase (AST) or alanine transaminase (ALT) >=2.5 time of institutional upper normal limit
Uncontrolled hypertension (systolic blood pressure >160mmHg or diastolic blood pressure >100mmHg)
Severe health problems not suitable for the study
Pregnant or lactating women
Hepatitis B or C