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

April 15, 2011 updated by: Kanazawa University

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

1. Objectives

  1. 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.
  2. To test whether sitagliptin enhances UDCA-induced beneficial effect in GLP-1 levels and glycemic control.
  3. To test safety of combination therapy of sitagliptin and UDCA in people with type 2 diabetes.

2. Clinical hypothesis.

  1. UDCA increases GLP-1 response to nutrients via provoking bile acids excretion from the liver to the intestine/colon.
  2. UDCA improves glycemic control in people with type 2 diabetes.
  3. Sitagliptin enhances UDCA-induced response of GLP-1 to nutrients.
  4. Sitagliptin has additive beneficial effects with UDCA in glycemic control in people with type 2 diabetes.
  5. Combination therapy of sitagliptin and UDCA is safe and well-tolerated in people with type 2 diabetes.
  6. 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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

20

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Japan
    • Ishikawa
      • Kanazawa, Ishikawa, Japan, 920-8641
        • Recruiting
        • Internal medicine, Kanazawa university hospital
        • Contact:
        • Sub-Investigator:
          • Kosuke R Shima, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

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

Exclusion Criteria:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
the difference of haemoglobin A1c (HbA1c) and glycoalbumin (GA)
Time Frame: 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.
6 months

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Kanazawa University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2010

Primary Completion (Anticipated)

March 1, 2013

Study Completion (Anticipated)

March 1, 2013

Study Registration Dates

First Submitted

September 16, 2010

First Submitted That Met QC Criteria

April 15, 2011

First Posted (Estimate)

April 18, 2011

Study Record Updates

Last Update Posted (Estimate)

April 18, 2011

Last Update Submitted That Met QC Criteria

April 15, 2011

Last Verified

April 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KanazawaU-1

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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