UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	Effects of pioglitazone and metformin on mitochondrial function evaluated with 31P MRS in type 2 DM.
Title of the study (Brief title)	31P MRS measurement of mitochondrial function and insulin resistance. (3M study)
Region	Japan

Condition
Condition	type 2 diabetes
Classification by specialty	Endocrinology and Metabolism
Classification by malignancy	Others
Genomic information	YES

Objectives
Narrative objectives1	1. To evaluate the correlation between the severity of insulin resistance and mitochondrial dysfunction of skeletal muscle in type 2 diabetes in Japan. (cross-sectional study) Using phosphorous-31 magnetic resonance spectroscopy(31P-MRS), we determine mitochondrial function of skeletal muscle by measuring phosphocreatine recovery half time(Pcr half time) immediately after exercise. We compare mitochondrial function with intramyocellular lipid content(IMCL), hepatic lipid content(HLC) measured with 1H-MRS, Glucose Infusion Rate(GIR) calculated by hyperinsulinemic-euglycemic glucose clamp and the amount of several adipocytokines. 2. To study whether insulin sensitizing agents(thiazolidinediones or biguanide) improve mitochondrial function of skeletal muscle, whether improvement of mitochondrial function correlate with the changes of IMCL, GIR, or adipocytokines.
Basic objectives2	Efficacy
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2	Pragmatic
Developmental phase	Phase IV

Assessment
Primary outcomes	Measurement of mitochondrial function of skeletal muscle before and after 24 weeks treatment with different insulin sensitizers.
Key secondary outcomes	1. Measurement of the amount of visceral fat, IMCL and HLC before and after 24 weeks treatment. 2. Measurement of GIR before and after 24 weeks treatment. 3. Measurement of FPG, IRI, HbA1c, total-cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol, FFA, adipocytokines before and after 24 weeks treatment. 4. Measurement of body weight and waist before and after 24 weeks treatment.

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Individual
Blinding	Open -no one is blinded
Control	Active
Stratification	YES
Dynamic allocation	YES
Institution consideration	Institution is not considered as adjustment factor.
Blocking	NO
Concealment	Pseudo-randomization

Intervention
No. of arms	2
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	pioglitazone (15-30mg/day)
Interventions/Control_2	metformin (750mg/day)
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	20 years-old <=
Age-upper limit	75 years-old >=
Gender	Male and Female
Key inclusion criteria	type 2 diabetes mellitus Japanese patients not used either thiazolidinediones nor biguanide.
Key exclusion criteria	1. Severe renal dysfunction(serum creatinine>2.0mg/dl) 2. Severe liver dysfunction(AST, ALT>50IU/ml) 3. Severe heart failure 4. History of hypersensitivity to pioglitazone or metformin 5. During the pregnancy or nursing 6. Arteriosclerosis obliterans (ASO) (ABI<0.9) 7. Poor control of plasma glucose (FPG>150mg/dl) 8. Inadequate to entry to this study
Target sample size	50

Research contact person
Name of lead principal investigator	Kazuhiko Sakaguchi
Organization	Kobe University Graduate School of Medicine
Division name	Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine
Address	7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017
TEL	078-382-5861
Email

Public contact
Name of contact person	Kazuhiko Sakaguchi
Organization	Kobe University Graduate School of Medicine
Division name	Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine
Address	7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017
TEL	078-382-5861
Homepage URL
Email	kzhkskgc@med.kobe-u.ac.jp

Sponsor
Institute	Kobe University Hospital
Institute
Department

Funding Source
Organization	None
Organization
Division
Category of Funding Organization	Self funding
Nationality of Funding Organization	Japan

Other related organizations
Co-sponsor	Kobe University Graduate School of Medicine Department of radiology
Name of secondary funｄer(s)

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions

Other administrative information
Date of disclosure of the study information	2007 Year 10 Month 01 Day

Progress
Recruitment status	Terminated
Date of protocol fixation	2007 Year 08 Month 16 Day
Anticipated trial start date	2007 Year 10 Month 01 Day
Last follow-up date	2008 Year 09 Month 01 Day
Date of closure to data entry	2009 Year 09 Month 30 Day
Date trial data considered complete
Date analysis concluded

Related information
URL releasing protocol
Publication of results	Unpublished
URL releasing results
Results
Other related information

Management information
Registered date	2007 Year 08 Month 30 Day
Last modified on	2017 Year 09 Month 06 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000000976