Endometrial Hyperplasia
Conditions
Brief 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.
Interventions
DRUGSemaglutide
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.
DRUGPlacebo
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.
Released via the levonorgestrel-releasing IUD.
BEHAVIORALTelemedicine behavioral weight program
Optional to attend.
Sponsors
Novo Nordisk A/S
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Masking description
Participant and pathologist
Intervention model description
Patients will be randomized on a 1:1 basis to either progestin + semaglutide 2.4 mg or progestin + placebo. Randomization will be stratified by previous progestin and metformin use.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of patients with endometrial hyperplasia free biopsy with uterine preservation | At 2 years (or exit from study) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to resolution of endometrial hyperplasia (EH) | Through completion of follow-up (estimated to be 4 years) | — |
| Change in weight | From baseline to 2 years | — |
| Change in Cancer Worry Impact of Events Scale (CWIES) | At enrollment, 12 months, and end of treatment (estimated to be 2 years) | 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. |
| Change in Impact of Weight on Quality of Life (IWQOL-Lite) | At enrollment, 12 months, and end of treatment (estimated to be 2 years) | 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. |
| Hyperplasia-free survival | Through completion of follow-up (estimated to be 4 years) | — |
Outcome results
None listed