Loxenatide Plus LNG-IUS in Endometrial Atypical Hyperplasia

NCT ID: NCT05172999

Last Updated: 2025-02-26

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-08
• Study Completion Date: 2026-06-30

Brief Summary

To study if polyethylene glycol loxenatide plus levonorgestrel-releasing intrauterine system (LNG-IUS) will improve response rates in patients with endometrial atypical hyperplasia.

Detailed Description

Background: Obesity or overweight is associated with lower treatment response and longer time to achieve complete response(CR) in patients with atypical endometrial hyperplasia (AEH) who want to preserve fertility, as evidenced by our research and lots of published studies. The larger the baseline weight of AEH patients, the more the weight gains after high-dose progesterone treatment. Obese AEH patients have a lower response to high-dose progesterone.

Losing weight may help improve treatment response. Weight management and lifestyle intervention have been written into 2020 uterine NCCN (National Comprehensive Cancer Network) guidelines. Our research showed that metformin may improve insulin resistance in patients with AEH, and shorten time to achieve CR, and increase the CR rates. Theoretically, Losing weight can improve the chronic inflammatory environment in the endometrium and whole body and improve metabolic disorder which help patients achieve CR.

LNG-IUS will be adopted in this research. Though LNG-IUS and high-dose progesterone have similar efficacy in treating AEH patients, long-term treatment of progesterone has many side effects. Compared to oral progesterone, LNG-IUS has fewer side effects and fewer effects on weight gaining.

GLP-1 receptor agonist (GLP-1RA), which is one of the commonly used hypoglycemic drugs, has been approved for weight control. Loxenatide is the first Chinese-produced long-acting GLP-1R agonist. It is applicable for diabetes patients. In the USA, some GLP-1RA has been applied for losing weight, such as liraglutide and semaglutide. GLP-1RA acts through improving insulin sensitivity, decreasing glucagon secretion, inhibiting appetite, delaying gastric emptying, and improving whole-body inflammation condition. Loxenatide plus LNG-IUS may improve the efficacy of preserving fertility in obese AEH patients through help patients lose weight.

Objective: To investigate whether loxenatide plus LNG-IUS improves the efficacy of preserving fertility when compared to LNG-IUS 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 software (version 22.0, IBM) to perform simple randomization and get randomized numbers. And participants will be randomly assigned (1:1) to receive LNG-IUS alone or loxenatide plus LNG-IUS. Patients in LNG-IUS alone group will accept LNG-IUS insertion as treatment and the other group cases will be treated with loxneatide plus LNG-IUS.

All enrolled patients will receive basic medical treatment in weight management and lifestyle improvement support, no enhanced interventions. Hysteroscopic assessment, metabolic and inflammatory indications will be performed every 12-16 weeks, while other indexes (weight, body composition change, side effects, and so on) will be evaluated every month.

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 (LNG-IUS alone verse LNG-IUS+ loxenatide) in 16-week. Secondary outcomes include CR rates in 32 weeks, assessment of ovarian functions, 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.

Conditions

Atypical Endometrial Hyperplasia; Obesity; Fertility Issues

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

LNG-IUS

enrolled patients will receive LNG-IUS for 6 months or longer till complete response

Group Type: ACTIVE_COMPARATOR

levonorgestrel-releasing intrauterine system

Intervention Type: DEVICE

Enrolled patients will be inserted this device for treating AEH to preserve fertility for 3-6 months or longer till complete response or operation if treatment fails, and the device may be removed if treatment changes.

LOX+LNG-IUS

enrolled patients will receive LNG-IUS plus polyethylene glycol loxenatide for treatment.

Group Type: EXPERIMENTAL

levonorgestrel-releasing intrauterine system

Intervention Type: DEVICE

Enrolled patients will be inserted this device for treating AEH to preserve fertility for 3-6 months or longer till complete response or operation if treatment fails, and the device may be removed if treatment changes.

Polyethylene Glycol Loxenatide

Intervention Type: DRUG

Initiate injection of Loxenatide will be 0.1mg per week, if the patient can tolerate, the dose will be increased to 0.2mg per week, or else 0.1mg per week will be injected and the injection will last for no more than 28 weeks. If the patient cannot tolerate the least 0.1mg/week, she must be excluded from this trial.

Interventions

levonorgestrel-releasing intrauterine system

Enrolled patients will be inserted this device for treating AEH to preserve fertility for 3-6 months or longer till complete response or operation if treatment fails, and the device may be removed if treatment changes.

Intervention Type: DEVICE

Polyethylene Glycol Loxenatide

Initiate injection of Loxenatide will be 0.1mg per week, if the patient can tolerate, the dose will be increased to 0.2mg per week, or else 0.1mg per week will be injected and the injection will last for no more than 28 weeks. If the patient cannot tolerate the least 0.1mg/week, she must be excluded from this trial.

Intervention Type: DRUG

Other Intervention Names

MIRENA; Fulaimei; PEX168

Eligibility Criteria

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
• Known or suspected pregnancy
• Currently suffering from pelvic inflammatory disease or diagnosed as pelvic inflammatory disease
• Lower reproductive system infection
• abnormal cervical dysplasia
• Congenital or acquired uterine abnormalities, including fibroids that deform the uterine cavity
• Allergic to any parts of LNG-IUS components
• The uterine cavity is too large (average diameter is over 7cm) or the history of LNG-IUS falling off

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Fudan University

OTHER

Sponsor Role: lead

Responsible Party

Xiaojun Chen

Principal Investigator，Clinical Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

XIAOJUN CHEN, PhD

Role: PRINCIPAL_INVESTIGATOR

Obstetrics & Gynecology Hospital of Fudan University

Locations

Obstetrics & Gynecology Hospital of Fudan University

Shanghai, Shanghai Municipality, China

Countries

China

Other Identifiers

53211033

Identifier Type: -

Identifier Source: org_study_id