Liraglutide Plus Megestrol Acetate in Endometrial Atypical Hyperplasia

March 23, 2021 updated by: Xiaojun Chen

Megestrol Acetate Versus Liraglutide Plus Megestrol Acetate in Obese Women With Endometrial Atypical Hyperplasia: A Randomized Controlled Pilot Clinical Study

To investigate the efficacy of liraglutide plus megestrol acetate in obesity patients with atypical endometrial hyperplasia (AEH)

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

Backgrounds: High-dose progesterone (MA/MPA) or LNG-IUS is the first-line treatment for women with atypical endometrial hyperplasia (AEH) or early endometrioid cancer who want to preserve fertility. About 70-80% of them can achieve complete response (CR) with the median time of 7-8 months. Over 10% of the patients can not achieve CR and choose operation finally. By the way, long-term treatment of progesterone has many side effects. Our previous study showed that overweight (BMI≥25kg/m2) AEH patients had a significantly increased risk of progesterone treatment failure, and the time to achieve CR is significantly prolonged. What's more, the greater the baseline weight of AEH patients, the greater the weight gains after high-dose progesterone treatment. Obese AEH patients have a lower response to high-dose progesterone. Weight management and lifestyle interventions are clearly written into 2020 uterine NCCN guidelines. We also find that metformin may improve insulin resistance in patients with AEH, and shorten time to achieve CR and increase the CR rates.

Liraglutide is a GLP-1 receptor agonist (GLP-1RA), which is one of the commonly used hypoglycemic drugs, has been approved for losing weight. And it is applicable for patients with BMI≥30 kg/m2 or ≥27 kg/m2 combined with one of the following: diabetes, hypertension, hyperlipidemia, sleep apnea. Liraglutide acts through improving insulin sensitivity, decreasing glucagon secretion , inhibiting appetite, delaying gastric emptying and improving whole-body inflammation condition.

Objective: To investigate whether liraglutide plus MA improve the efficacy of preserving fertility when compared to MA alone in obese women with AEH who want fertility conservation.

Design: A pilot prospective randomized controlled study is designed. And this study is open-label. We use SPSS (version 22.0,IBM) to design simple randomization. And participants will be randomly assigned (1:1) to receive MA alone or liraglutide plus MA. Patients in MA alone group will receive MA 160mg po qd and patients in the liraglutide plus MA group will receive liraglutide additionally with dose of 1.8mg/d or the max tolerance dose.

All enrolled patients will receive mentoring in weight management and lifestyle improvement. Hysteroscopic assessment will be performed every 12-16 weeks while other indexes will be evaluated every month, including weight, metabolic indications，inbody fat analysis, inflammation indicators and so on.

For the efficacy evaluation, CR is defined as the reversion of endometrial atypical hyperplasia to proliferative or secretory endometrium; partial response (PR) is defined as regression to simple or complex hyperplasia without atypia; no response (NR) is defined as the persistence of the disease; and progressive disease (PD) is defined as the appearance of endometrial cancer in patients. Continuous therapies will be needed in PR, NR or PD. Two months of maintenance treatment will be recommended for patients with CR, and participants will be followed up for 2 years.

Outcomes: Primary outcome is the CR rates of the two groups (MA alone VS MA+ liraglutide) . secondary outcomes include improvement of weight, insulin resistance, chronic inflammation condition, and time to achieve CR, and safety and side events during the therapy, and the recurrence rates, pregnancy rates and live birth rates in two years.

Study Type

Interventional

Phase

  • Phase 2
  • Phase 3

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • BMI (body mass index) ≥28kg/m2
  • Consent informed and signed
  • Pathologically confirmed as endometrial atypical hyperplasia
  • Have a strong desire to reproduce and ask for fertility preservation or those who insist on keeping the uterus despite no reproductive requirements
  • Have good compliance and follow-up conditions, and patients are willing to follow up in Obstetrics and Gynecology Hospital of Fudan University in time

Exclusion Criteria:

  • Diagnosed as type 2 diabetes
  • Diabetic ketoacidosis
  • History of acute pancreatitis
  • Have a history or family history of medullary thyroid carcinoma; multiple endocrine neoplasia syndrome type 2 (MEN2)
  • Combined with severe medical disease or severely impaired liver and kidney function
  • Patients with other types of endometrial cancer or other malignant tumors of the reproductive system; patients with breast cancer or other hormone-dependent tumors that cannot be used with progesterone
  • Those who require hysterectomy or other methods other than conservative treatment with drugs
  • Deep vein thrombosis, stroke, myocardial infarction
  • Smokers (≥15 cigarettes/day)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: MA alone
enrolled patients will receive megestrol acetate 160mg po qd
Drug: Megestrol Acetate 160 MG
160mg po qd
Other Names:
  • Megace
  • Yi li zhi
Experimental: MA+liraglutide
enrolled patients will receive megestrol acetate 160mg po qd plus liraglutide (1.8mg/d or the max tolerable dosage)
Drug: Megestrol Acetate 160 MG
160mg po qd
Other Names:
  • Megace
  • Yi li zhi
Drug: Liraglutide Injection
Initiate liraglutide with a dose of 0.6 mg daily for one week. After one week at 0.6 mg per day, increase the dose to 1.2 mg daily in a week, and increase the dose to 1.8 mg daily after at least one week of treatment with the 1.2 mg daily dose. If the patients can not tolerate 1.8mg per day, decrease the dose to the max tolerable dose.
Other Names:
  • victoza
  • Nuo he li

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pathological complete response (CR) rates
Time Frame: From date of randomization until the date of CR, assessed up to 28 weeks.
The 28-week CR rates will be calculated in two groups
From date of randomization until the date of CR, assessed up to 28 weeks.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Relapse rates
Time Frame: up to 2 years after the treatment for each patient
All enrolled patients will be followed up for 2 years. During the following-up period, if patients recur after complete regression, they will be counted and the number of recurrence will be divided by number of patients followed up, then we can get the relapse rates.Comparison will be performed between two groups.
up to 2 years after the treatment for each patient
pregnancy outcomes
Time Frame: up to 2 years after the treatment for each patient
For patients have a desire for fertility, pregnancies, births and related outcomes will be counted, and the rate of pregnancy will be counted as number of pregnancies/ number of patients trying to fertility in the following period. Comparison will be performed between two groups
up to 2 years after the treatment for each patient
weight lose
Time Frame: From date of randomization until the date of CR, assessed up to 28 weeks
weight changing in 28-week's intervention, weight will be recorded every 4 weeks.
From date of randomization until the date of CR, assessed up to 28 weeks
changing of insulin resistance
Time Frame: From date of randomization until the date of CR, assessed up to 28 weeks.
Glycated hemoglobin，Glucose tolerance test，Insulin release test，and C peptide release test will be performed at baseline and 28-week. During 12-16 week, fasting glucose, insulin, glycated hemoglobin and fasting C peptide will be tested once.
From date of randomization until the date of CR, assessed up to 28 weeks.
improvement of chronic inflammation
Time Frame: From date of randomization until the date of CR, assessed up to 28 weeks
improvement of chronic inflammation indications in 28 weeks. In detail, indicators including TNF-α、IL-1, IL-6 and Creatine Kinase will be tested at 0,12-16th and 28th week.
From date of randomization until the date of CR, assessed up to 28 weeks
Time of pathological complete response (CR)
Time Frame: From date of randomization until the date of CR, assessed up to 2 years.
Time of histologic regression from AEH to proliferative or secretory endometrium
From date of randomization until the date of CR, assessed up to 2 years.
safety and side effects
Time Frame: From date of randomization until the date of CR, assessed up to 2 years.
Adverse events related with Liraglutide and MA. Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 will be recorded, as well as incidence of adverse events.
From date of randomization until the date of CR, assessed up to 2 years.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Xiaojun Chen

Collaborators

Huashan Hospital

Investigators

  • Principal Investigator: xiaojun chen, Obstetrics & Gynecology Hospital of Fudan University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

March 20, 2021

Primary Completion (Anticipated)

November 30, 2022

Study Completion (Anticipated)

November 30, 2024

Study Registration Dates

First Submitted

December 17, 2020

First Submitted That Met QC Criteria

December 23, 2020

First Posted (Actual)

December 24, 2020

Study Record Updates

Last Update Posted (Actual)

March 25, 2021

Last Update Submitted That Met QC Criteria

March 23, 2021

Last Verified

March 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 53211031

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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