Longitudinal Follow-up in Women With Endometrial Hyperplasia Without Atypia

MicroRNAs as Biomarkers of Predicting Future Endometrial Malignancy and Longitudinal Follow-up With Randomized Intervention in Women With Endometrial Hyperplasia Without Atypia

This study will prospectively enroll a total of 1000 patients (200 per year) simple hyperplasia/complex hyperplasia (SH/CH) without atypia. All subjects will receive education for exercise and weight control and be randomized 1:1 to with or without metformin intervention. At the end of this 3-year project, an interim analysis will be performed. Since long-term follow-up is intended, therefore for the 4th to 6th year a new grant support will be looked for. The long-term occurrence of endometrial cancer (up to15 years) data will be acquired from national cancer registry, which permission is addressed in the informed sent.

Study Overview

• Status: Recruiting
• Conditions: Female
• Intervention / Treatment: Drug: Metformin

Detailed Description

The first year: (1) the cumulative progression rate of SH/CH without atypia to endometrial cancer (EC) of the 1989-2011 cohort will be investigated by linking with national health databases from Health and Welfare Data Science Center (HWDC); (2) Prospectively enroll 200 patients with SH/CH without atypia and deliver education for exercise and weight control and collect the related biospecimens and data; (3) 1:1 randomized to with or without metformin intervention.

The 2nd year: (1) analyze the whole genome sequencing (WGS) data of those progressed and non-progressed ; (2) analyze the metabolomic data in relation to exercise and weight control data.

The 3rd year: (1) validate microRNA (miR) panel in tissues and sera selected by CMRPG3G1511-3; (2) analyze data of MiR panel, degree of exercise/weight control, clinical lab data, and demographic data on EC progression rate; (3) Incremental predicting proficiency of the model including metabolomics data and WGS.

• Study Type: Interventional
• Enrollment (Anticipated): 1000
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: CHYONG-HUEY LAI, M.D.; Phone Number: 8254 +88633281200; Email: laich46@cgmh.org.tw

Study Locations

• Taiwan
  • Taoyuan, Taiwan, 333
    • Recruiting
    • Chang Gung Memorial Hospital, Linkou Branch
    • Contact: CHYONG-HUEY LAI, M.D.; Phone Number: 8254 +88633281200; Email: laich46@cgmh.org.tw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Women aged ≧ 20 years
2. Histological diagnosis of SH/CH without atypia
3. Not taking Metformin for diabetes mellitus currently
4. Adequate kidney function
5. Provided informed consent within 3 months of diagnosis
6. No previous history of breast cancer with tamoxifen use
7. Willing to be followed for 5 years

Exclusion Criteria:

1. Atypical hyperplasia or EC found within 3 months after enrollment
2. History or concurrent gynecologic cancers or cervical intraepithelial neoplasia
3. Pregnancy test positive
4. History of intolerance to Metformin
5. Family history of HNPCC

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: metformin group; During the intervention period, metformin is given 500 mg tablet b.i.d.; We will deliver education for exercise and weight control to all eligible participants	Drug: Metformin; During the intervention period, metformin is given 500 mg tablet b.i.d. Those who stopped taking metformin will remain in the study not counting as protocol violation.; Other Names: Uformin Tablet 500mg
No Intervention: Observation group; only exercise and weight control to all eligible participants

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The area under the receiver operating characteristic curve (ROC curve) (AUC) of the prediction miR panel of the 3 miRs.	The primary endpoint of the randomized prospective study is to evaluate the ROC of the prediction miR panel of the 3 miRs.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to progression among groups	Incidence of progression to endometrial cancer among groups, Proportion of participants with treatment-related adverse events as assessed by CTCAE v4.0	3 years
Subgroup analysis in body-weight control	Follow up the body-weight control	3 years

Collaborators and Investigators

• Sponsor: Chang Gung Memorial Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2018
• Primary Completion (Anticipated): October 1, 2022
• Study Completion (Anticipated): January 29, 2026

Study Registration Dates

• First Submitted: August 4, 2021
• First Submitted That Met QC Criteria: March 14, 2022
• First Posted (Actual): March 23, 2022

Study Record Updates

• Last Update Posted (Actual): March 23, 2022
• Last Update Submitted That Met QC Criteria: March 14, 2022
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: simple hyperplasia; Metformain
• Additional Relevant MeSH Terms: Pathologic Processes; Uterine Diseases; Hyperplasia; Endometrial Hyperplasia; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: 107-2314-B-182A-166-MY3

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No