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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified April 2011 by Kanazawa University.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Kanazawa University
ClinicalTrials.gov Identifier:
NCT01337440
First received: September 16, 2010
Last updated: April 15, 2011
Last verified: April 2011
  Purpose

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.

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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Kanazawa University:

Primary Outcome Measures:
  • the difference of haemoglobin A1c (HbA1c) and glycoalbumin (GA) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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%) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Change from Baseline in energy expenditure [ Time Frame: 6months ] [ Designated as safety issue: No ]
  • Change from Baseline in fasting plasma glucose level [ Time Frame: 6months ] [ Designated as safety issue: No ]
  • change from baseline in autonomic nerve function [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    This is performed by power-spectrum analyses of heart rate variability


Estimated Enrollment: 20
Study Start Date: April 2010
Estimated Study Completion Date: March 2013
Estimated Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: Ursodeoxycholic acid (UDCA) goes by the trade names Urso.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01337440

Contacts
Contact: Toshinari Takamura, MD, PhD +81-76-265-2233 ttakamura@m-kanazawa.jp

Locations
Japan
Internal medicine, Kanazawa university hospital Recruiting
Kanazawa, Ishikawa, Japan, 920-8641
Contact: Toshinari Takamura, MD, PhD    +81-76-265-2233    ttakamura@m-kanazawa.jp   
Sub-Investigator: Kosuke R Shima, MD         
Sponsors and Collaborators
Kanazawa University
  More Information

Publications:

Responsible Party: BANYU TOKYO, Merck & Co., Inc.
ClinicalTrials.gov Identifier: NCT01337440     History of Changes
Other Study ID Numbers: KanazawaU-1
Study First Received: September 16, 2010
Last Updated: April 15, 2011
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by Kanazawa University:
Ursodeoxycholic Acid
sitagliptin
bile acids
GLP-1

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Liver Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Digestive System Diseases
Ursodeoxycholic Acid
Sitagliptin
Dipeptidyl-Peptidase IV Inhibitors
Cholagogues and Choleretics
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014