Mechanisms of action of hypoglycemic drugs in nonalcoholic fatty liver disease (NAFLD)

ISRCTN ISRCTN33414972
DOI https://doi.org/10.1186/ISRCTN33414972
Secondary identifying numbers N/A
Submission date
30/11/2013
Registration date
16/12/2013
Last edited
13/02/2017
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Nutritional, Metabolic, Endocrine
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Background and study aims
Nonalcoholic fatty liver disease (NAFLD) has attracted considerable attention as a cause of type 2 diabetes. Although no full-scale survey has been conducted in Japan, it is highly expected that the number of patients with NAFLD will increase rapidly with the advancing westernization of eating habits.

Who can participate?
Participants are diabetic males, aged 40-70 years, who are previously untreated for type 2 diabetes (T2DM).

What does the study involve?
Participants will be classified into two groups based on the presence or absence of NAFLD. The participants with NAFLD will be randomly allocated to one of four groups and treated with pioglitazone, metformin or sitagliptin, or a non-antidiabetic drug (non-OAD), for 6 months. In the non-OAD group, participants are provided with dietary and exercise guidance. The participants in the non-NAFLD group will be referred to their respective attending physicians as outpatients for the treatment of diabetes.

What are the possible benefits and risks of participating?
Participants will receive information on their body composition and blood pressure. Possible risks would be adverse effects from antidiabetic drugs. Although computed tomography (CT) poses no significant risk associated with the use of contrast medium, patients may be exposed to some (permissible) dose of radiation.

Where is the study run from?
Second Department of Internal Medicine, Ryukyus University Hospital (Japan)

When is the study starting and how long is it expected to run for?
August 2010 to December 2012

Who is funding the study?
University of the Ryukyus (Japan)

Who is the main contact?
Dr Kouichi Yabiku

Contact information

Dr Kouichi Yabiku
Scientific

207 Uehara Nishihara-cho
Nakagami-gun
903-0215
Japan

Study information

Study designRandomized parallel group trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details to request a patient information sheet
Scientific titleMechanisms of action of hypoglycemic drugs in nonalcoholic fatty liver disease (NAFLD): elucidation of its association with 'inflammation'
Study objectivesSeveral oral antidiabetic drugs (OADs) will be effective treatments for NAFLD.
Ethics approval(s)Ethics Committee of the Faculty of Medicine at the University of the Ryukyus, 09/03/2010, No. 122
Health condition(s) or problem(s) studiedNonalcoholic fatty liver disease, type 2 diabetes
InterventionPatients are divided into NAFLD and non-NAFLD groups by abdominal ultrasound.

The patients with NAFLD will be then randomly allocated to receive either pioglitazone (30 mg/day), metformin (1 g/day), sitagliptin (50 mg/day) or a non-antidiabetic drug (non-OAD). In the non-OAD group, all subjects are provided with dietary and exercise guidance. Abdominal CT is performed before and after the trial, and changes in NAFLD activity are evaluated.

The patients in the non-NAFLD group are referred to their respective attending physicians as outpatients for the treatment of diabetes, and those in the above monotherapy groups or non-antidiabetic drug group similarly undergo abdominal CT and blood tests before and after the trial.

All subjects are provided with dietary and exercise guidance once a month during the study (6 months).
Intervention typeDrug
Pharmaceutical study type(s)
PhaseNot Applicable
Drug / device / biological / vaccine name(s)Pioglitazone, metformin, sitagliptin
Primary outcome measureDifferences between baseline and end-of-treatment liver to spleen (L/S) ratios determined by CT and physical findings (blood pressure, body mass index and waist circumference) will be measured in each group.
Blood samples will be obtained to measure concentrations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), cholinesterase, fasting plasma glucose, fasting insulin, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), triglycerides, non-esterified fatty acids (NEFA), high-sensitivity C-reactive protein (hsCRP), soluble tumor necrosis factor receptors 1 (sTNFR-1), and 2 (sTNFR-2), high-molecular-weight (HMW) adiponectin, and ferritin.
Secondary outcome measuresNo secondary outcome measures
Overall study start date01/08/2010
Completion date27/12/2012

Eligibility

Participant type(s)Patient
Age groupAdult
SexMale
Target number of participants800
Key inclusion criteria1. Diabetic males aged 40-70 years
2. Previously untreated for type 2 diabetes (T2DM)
3. Body mass index (BMI) >25 kg/m2
4. Glycated hemoglobin (HbA1c) of 6.4-7.9% (National Glycohemoglobin Standardization Program units)
5. Fasting plasma glucose of 126-261 mg/dl
Key exclusion criteria1. Patients with mental disorders, including alcohol dependence, or with such a history
2. Patients with pancreatitis
3. Patients with malignant diseases
4. Patients with viral hepatitis
5. Patients who have participated in any clinical study or trial within 6 months
6. Patients experiencing a weight gain or loss of 1 kg or more within 3 months before the start of the trial
7. Patients deemed ineligible for the trial
Date of first enrolment01/08/2010
Date of final enrolment27/12/2012

Locations

Countries of recruitment

  • Japan

Study participating centre

207 Uehara Nishihara-cho
Nakagami-gun
903-0215
Japan

Sponsor information

University of Ryukyus (Japan)
University/education

207 Uehara Nishihara-cho
Nakagami-gun
903-0215
Japan

ROR logo "ROR" https://ror.org/02z1n9q24

Funders

Funder type

University/education

University of Ryukyus (Japan)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 01/03/2017 Yes No

Editorial Notes

13/02/2017: Publication reference added.