UMIN-CTR Clinical Trial

Basic information
Public title	Effect of metformin on the endometrium of obese, insulin-resistant women
Acronym	Effect of metformin on the endometrium of obese, insulin-resistant women
Scientific Title	Effect of metformin on the endometrium of obese, insulin-resistant women
Scientific Title:Acronym	Effect of metformin on the endometrium of obese, insulin-resistant women
Region	Japan

Condition
Condition	obese, insulin-resistant women
Classification by specialty	Obsterics and gynecology
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	This study will investigate the antiproliferative effects of metformin on the endometrium of obese, insulin-resistant women. The changes in serum levels of insulin, insulin-like growth factor-1 (IGF-1), adipocytokines (leptin and adiponectin); body mass index (BMI); and insulin resistance will be evaluated after metformin intake.
Basic objectives2	Efficacy
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2	Others
Developmental phase	Not applicable

Assessment
Primary outcomes	To evaluate the effect of metformin on phospho-ERK expression in the endometrium
Key secondary outcomes	1. To evaluate the effect of metformin on biomarker expression in the endometrium. Differences in Ki-67 and topoisomeraseIIa; expression will be assessed immunohistochemically.Phospho-AKT, phospho-AMPK, phospho-rpS6, cyclin D1, pRB, and p27 will be assessed using western blot analysis. 2. To evaluate the effect of metformin on serum biomarkers, such as insulin, IGF-1, and adipocytokines, such as leptin and adiponectin. 3. To evaluate the changes in BMI and insulin resistance after metformin treatment. 4. To evaluate the changes in the growth-stimulatory potential of sera after metformin treatment.

Base
Study type	Interventional

Study design
Basic design	Single arm
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	Uncontrolled
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	1
Purpose of intervention	Prevention
Type of intervention	Medicine
Interventions/Control_1	1) Patients will receive a daily dose of metformin (initial dose, 500 mg/day; increasing, weekly, up to 1500 mg/day, in the absence of adverse effects) for 3 months 2) Blood samples and endometrial biopsies will be obtained at baseline and after 3 months.
Interventions/Control_2
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	45 years-old >=
Gender	Female
Key inclusion criteria	1. Normal endometrium or simple hyperplasia, without atypia. 2. BMI 25 and over and a positive test for insulin resistance 3. Menstrual irregularity 4. Aged between 20- and 45-years-old 5. Eastern Cooperative Oncology Group Performance status 0 6. Provided written informed consent
Key exclusion criteria	1. Prior medical history of chemical sensitivity to metformin 2. Women desiring to become pregnant during the study period 3. Serum creatinine level >1.0 mg/dL 4. History of lactic acidosis 5. Requiring dialysis 6. Shock, cardiac arrest, cardiac infarction, pulmonary thrombosis, or severe cardiovascular and/or lung damage 7. Ingestion of excessive amounts of alcohol 8. Liver dysfunction 9. History of thrombosis 10. Mental illness that may require antipsychotic therapy 11. Diabetes mellitus requiring medication 12. Concomitant malignancies 13. Ineligible, as determined by the physician-in-charge for any other reason
Target sample size	15

Research contact person
Last name of lead principal investigator	1st name AKIRA Middle name Last name Mitsuhashi
Organization	Graduate School of Medicine, Chiba University,
Division name	Reproductive Medicine
Zip code	260-8670
Address	1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan
TEL	043-222-7171
Email	antira@faculty.chiba-u.jp

Public contact
1st name of contact person	1st name AKIRA Middle name Last name Mitsuhashi
Organization	Graduate School of Medicine, Chiba University
Division name	Reproductive Medicine
Zip code	260-8670
Address	1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan
TEL	043-222-7171
Homepage URL
Email	antira@faculty.chbia-u.jp

Sponsor
Institute	Graduate School of Medicine, Chiba University
Institute
Department

Funding Source
Organization	The Japan Society for Promotion of Science
Organization
Division
Category of Funding Organization	Japanese Governmental office
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funder(s)

IRB Contact (For public release)
Organization	Chiba University Hospital
Address	1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan
Tel	043-222-7171
Email	hanaoka.hideki@faculty.chiba-u.jp

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	2014 Year 10 Month 20 Day

Related information
URL releasing protocol
Publication of results	Unpublished

Result
URL related to results and publications
Number of participants that the trial has enrolled
Results
Results date posted
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics
Participant flow
Adverse events
Outcome measures
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Completed
Date of protocol fixation	2014 Year 10 Month 14 Day
Date of IRB	2014 Year 10 Month 14 Day
Anticipated trial start date	2014 Year 10 Month 20 Day
Last follow-up date	2019 Year 03 Month 31 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information

Management information
Registered date	2014 Year 10 Month 19 Day
Last modified on	2019 Year 04 Month 23 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000017984