Primary Prevention and Uterine Preservation in Premenopausal Women With Obesity and Endometrial Hyperplasia

Launched by WASHINGTON UNIVERSITY SCHOOL OF MEDICINE · Apr 24, 2023

Keywords

ClinConnect Summary

This clinical trial is looking at a new treatment approach for premenopausal women who have been diagnosed with a condition called endometrial hyperplasia, which is an abnormal thickening of the lining of the uterus. The researchers want to see if combining two treatments—semaglutide, a medication that can help with weight loss, and a small device called an LNG-IUD that releases hormone therapy—can help preserve the uterus, support weight loss, and improve overall health and quality of life. This study is currently recruiting participants who are female, between the ages of 18 and 45, and have a body mass index (BMI) of 30 or higher.

To be eligible for the trial, women must have a confirmed diagnosis of a specific type of endometrial hyperplasia and be interested in keeping their uterus for future pregnancies. Participants will need to agree to have the LNG-IUD placed at the start of the study. Throughout the trial, participants can expect to receive careful monitoring and support, and they will be contributing to important research that could help women facing similar health challenges in the future. It's important to note that specific health conditions may exclude some women from participating, so potential participants should discuss their medical history with their healthcare provider.

Gender

FEMALE

Eligibility criteria

• Inclusion Criteria:
• • Diagnosis of histologically confirmed complex atypical endometrial hyperplasia.
• • Patients with a previous diagnosis of AEH who are already being followed with conservative management with oral or LNG-IUD progestin therapy are eligible provided they have not previously been on a GLP-1R agonist within 3 months prior to enrollment.
• • For patients with a previous diagnosis of AEH who have been placed on progestin prior to study entry, the duration of IUD or oral progestin use prior to trial entry should be less than or equal to 6 months.
• • Premenopausal woman with a uterus.
• • At least 18 years of age and no more than 45 years of age.
• • Interested in uterine preservation/fertility-sparing treatment.
• • BMI ≥ 30 kg/m2.
• • Prior or current receipt of progestin is allowed as above. Willingness to undergo placement of LNG-IUD at the time of study entry.
• • Prior or current receipt of metformin is allowed.
• • Ability to understand and willingness to sign an IRB approved written informed consent document.
• Exclusion Criteria:
• • Prior use of GLP-1 receptor agonist (exenatide, liraglutide, or other) or pramlintide or any DPP-4 inhibitor in the 3 months prior to date of registration.
• • History of type 1 or type 2 diabetes, and/or the following biochemical indications: fasting plasma glucose ≥ 126 mg/dL, HbA1c ≥ 6.5%, two-hour plasma glucose ≥ 200 mg/dL during an oral glucose tolerance test (OGTT), or random glucose ≥ 200 mg/dL in the presence of symptoms
• • Acute decompensation of glycemic control.
• • Concomitant use of other weight management drugs or drugs for short-term weight loss.
• • History of surgery or use of a device to treat obesity.
• • Uncontrolled thyroid disease
• • Acute coronary or cerebrovascular event in the previous 60 days.
• • Currently planned coronary, carotid, or peripheral artery revascularization.
• • Chronic heart failure (NYHA class IV).
• • Evidence of renal dysfunction as defined by creatinine clearance \< 60 ml/minute.
• • History of solid organ transplant or awaiting solid organ transplant.
• • Diagnosis of any malignant neoplasm or current, active treatment with chemotherapy or radiation.
• • Family or personal history of multiple endocrine neoplasia syndrome type 2 (MEN 2) or familial medullary thyroid carcinoma (MTC).
• • A history of allergic reactions attributed to compounds of similar chemical or biologic composition to progestin, semaglutide, or other agents used in the study.
• • History of diabetic retinopathy.
• • Recent history of pancreatitis, defined as less than 6 months prior to enrollment.
• • History of suicidal attempts or active suicidal ideation.
• • Significant active psychiatric disease, including recent psychiatric inpatient admission or use of any psychiatric medications that are not stabilized.
• • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
• • Pregnant and/or breastfeeding. Participants must have a negative serum pregnancy test within 7 days of date of registration.
• • Patients with HIV are eligible unless their CD4+ T-cell counts are \< 350 cells/mcL, they have a history of AIDS-defining opportunistic infection within the 12 months prior to registration, or they are receiving anti-retrovirals that affect progestin levels. Concurrent treatment with effective ART according to DHHS treatment guidelines is recommended.