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

Endometrial Hyperplasia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05829460
• Other study ID #: 202402083
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: June 30, 2024
• Est. completion date: June 30, 2031

Study information

• Verified date: May 2024
• Source: Washington University School of Medicine
• Contact: Andrea R Hagemann, M.D., MSCI
• Phone: 314-362-1763
• Email: hagemanna[@]wustl.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 96
• Est. completion date: June 30, 2031
• Est. primary completion date: June 30, 2029
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

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.

Related Conditions & MeSH terms

• Endometrial Hyperplasia
• Hyperplasia

Intervention

Drug:
• Semaglutide
This medication is self-administered as a subcutaneous injection in the abdomen, thigh, or upper arm; injection site should be rotated when using the same body region.
• Placebo
This medication is self-administered as a subcutaneous injection in the abdomen, thigh, or upper arm; injection site should be rotated when using the same body region.
• LNG-IUD (Progestin)
Released via the levonorgestrel-releasing IUD.

Behavioral:
• Telemedicine behavioral weight intervention
Weekly telephone calls during the first year and then monthly during the second year. Each telephone session will be 30 minutes long.

Locations

Country	Name	City	State
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Washington University School of Medicine	Novo Nordisk A/S

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients with atypia-free biopsy with uterine preservation		At 2 years (or exit from study)
Secondary	Time to resolution of hyperplasia		Through completion of follow-up (estimated to be 4 years)
Secondary	Change in weight		From baseline to 2 years
Secondary	Change in Cancer Worry Impact of Events Scale (CWIES)	The CWIES is a 15-item self-report measure evaluating stress reactions and traumatic experiences, specifically inquiring about cancer worry-specific distress. Range of values for each individual item will be a Likert Scale from 0-5. 0=not at all and 5=often. The higher the score, the more cancer-worry specific distress the participant has.	At enrollment, 12 months, and end of treatment (estimated to be 2 years)
Secondary	Change in Impact of Weight on Quality of Life (IWQOL-Lite)	The IWQOL-Lite provides a total score and scores for five subscales: physical function, self-esteem, sexual life, public distress and work. Scores range from 0 to 100 with lower scores indicating greater impairment.	At enrollment, 12 months, and end of treatment (estimated to be 2 years)
Secondary	Atypia free survival		Through completion of follow-up (estimated to be 4 years)

External Links

•   Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine