Plain English Summary
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
Trial website
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
N/A
Study information
Scientific title
Mechanisms of action of hypoglycemic drugs in nonalcoholic fatty liver disease (NAFLD): elucidation of its association with 'inflammation'
Acronym
Study hypothesis
Several oral antidiabetic drugs (OADs) will be effective treatments for NAFLD.
Ethics approval
Ethics Committee of the Faculty of Medicine at the University of the Ryukyus, 09/03/2010, No. 122
Study design
Randomized parallel group trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
Nonalcoholic fatty liver disease, type 2 diabetes
Intervention
Patients 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 type
Drug
Phase
Not Applicable
Drug names
Pioglitazone, metformin, sitagliptin
Primary outcome measure
Differences 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 measures
No secondary outcome measures
Overall trial start date
01/08/2010
Overall trial end date
27/12/2012
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. 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
Participant type
Patient
Age group
Adult
Gender
Male
Target number of participants
800
Participant exclusion criteria
1. 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
Recruitment start date
01/08/2010
Recruitment end date
27/12/2012
Locations
Countries of recruitment
Japan
Trial participating centre
207 Uehara Nishihara-cho
Nakagami-gun
903-0215
Japan
Funders
Funder type
University/education
Funder name
University of Ryukyus (Japan)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2017 results in: https://www.ncbi.nlm.nih.gov/pubmed/28185715