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

The Washington University

Status and phase: Withdrawn; Phase 2

Conditions: Endometrial Hyperplasia

Treatments: Behavioral: Telemedicine behavioral weight program; Drug: LNG-IUD (Progestin); Drug: Placebo; Drug: Semaglutide

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT05829460

202402083

Details and patient eligibility

About

The investigators hypothesize that combined treatment with the GLP-1R agonist semaglutide 2.4 mg and levonorgestrel intrauterine device (LNG-IUD), compared to LNG-IUD alone, will result in improved likelihood of uterine preservation, sustained weight loss, improved endometrial and metabolomic response to progestin, and improved quality of life in premenopausal women with endometrial hyperplasia who desire uterine preservation.

Sex: Female

Ages: 18 to 45 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosis of histologically confirmed non-atypical endometrial hyperplasia (EH) or complex atypical endometrial hyperplasia (AEH).

  • Patients with a previous diagnosis of EH or 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 EH or 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 diabetes.
• History of type 2 diabetes requiring use of insulin.
• 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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0 participants in 2 patient groups

Arm 1: Semaglutide + progestin

Experimental group

Description:

* The progestin will be delivered via the levonorgestrel-releasing IUD and it is standard of care. * Will receive injectable pens containing semaglutide and will be self-administered on a weekly basis for up to 104 weeks. Dosing will be escalated during weeks 1 through 16 (start at 0.25 mg up to 2.4 mg). * Will be enrolled in a behavioral weight program that is optional to attend. The program will be delivered in a closed-group format. The group program will consist of 12 consecutive 60 minute weekly visits, and will recur every three months such that participants can join the soonest available Week 1 session after study enrollment. Each group session will focus on providing education and cognitive/behavioral strategies to achieve a healthier, reduced-calorie diet and a more physically active lifestyle. Cognitive/behavioral strategies will consist of goal setting, problem solving, cognitive restructuring, stimulus control, and stress management.

Treatment:

Drug: Semaglutide

Drug: LNG-IUD (Progestin)

Behavioral: Telemedicine behavioral weight program

Arm 2: Placebo + Progestin

Active Comparator group

Description:

* The progestin will be delivered via the levonorgestrel-releasing IUD and it is standard of care. * Will receive injectable pens containing the placebo and will be self-administered on a weekly basis for up to 104 weeks. * Will be enrolled in a behavioral weight program that is optional to attend. The program will be delivered in a closed-group format. The group program will consist of 12 consecutive 60 minute weekly visits, and will recur every three months such that participants can join the soonest available Week 1 session after study enrollment. Each group session will focus on providing education and cognitive/behavioral strategies to achieve a healthier, reduced-calorie diet and a more physically active lifestyle. Cognitive/behavioral strategies will consist of goal setting, problem solving, cognitive restructuring, stimulus control, and stress management.

Treatment:

Drug: Placebo

Drug: LNG-IUD (Progestin)

Behavioral: Telemedicine behavioral weight program