A Phase 2 interventional study of Semaglutide (Wegovy) weekly injection and LNG-IUD (Progestin) in Endometrial Atypical Hyperplasia, Endometrial Atypical Hyperplasia/Endometrioid Intraepithelial Neoplasia and Endometrial Cancer Stage I, sponsored by The Methodist Hospital Research Institute. Not yet recruiting at 4 sites in United States. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-01.
Sponsored by The Methodist Hospital Research Institute · Phase 2, Interventional, and Treatment
The goal of this clinical trial is to learn if a combination treatment of a hormonal intrauterine device (LNG-IUD), semaglutide, and a structured weight loss program can treat endometrial atypical hyperplasia or grade 1 endometrioid endometrial cancer while preserving fertility in women of reproductive age with endometrial atypical hyperplasia (EAH) or FIGO grade 1 endometrioid endometrial cancer who wish to preserve their fertility. The main questions it aims to answer are:
Participants will:
110 studies on the registry are indexed under Endometrial Hyperplasia; 38 are open to participants now.
This study's planned enrollment of 48 is below the median of 80 across 71 interventional studies indexed under Endometrial Hyperplasia.
Browse Endometrial Hyperplasia studies →The Methodist Hospital Research Institute is the lead sponsor of 160 studies on the registry; 59 are open to participants now.
Of its 28 completed or terminated interventional studies of FDA-regulated products, 18 (64%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Imaging eligibility (for patients with endometrial cancer):
Treatment Rationale (at least one of the following must apply):
i. Class III obesity ( ≥40 kg/m²); or ii. ASA Physical Status Classification score ≥3.
Progestin washout: patients with prior progestin exposure are eligible provided the following minimum have been observed.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
A planned gap after a treatment, so that its effects can lessen before the study treatment or a study assessment. Ask the study team and the doctor who prescribed it before changing any medicine.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Washout period
A planned gap after a treatment, so that its effects can lessen before the study treatment or a study assessment. Ask the study team and the doctor who prescribed it before changing any medicine.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants will receive a three-component combination intervention consisting of: (1) a levonorgestrel-releasing intrauterine device (LNG-IUD), inserted at baseline; (2) semaglutide 2.4 mg, administered per standard dosing schedule; and (3) a structured weight loss program. Participants will undergo hysteroscopy with endometrial sampling to assess pathological response. Treatment will be administered for 6 months of active intervention, followed by a 6-month follow-up period.
Drug: Semaglutide (Wegovy) weekly injection · Device: LNG-IUD (Progestin) · Behavioral: Structured Weight Loss Program
Semaglutide 2.4 mg administered subcutaneously once weekly, following standard dose-escalation protocol, for the duration of the 6-month active treatment period. Used off-label in this trial for its metabolic effects in combination with LNG-IUD, rather than as monotherapy for weight loss.
Levonorgestrel-releasing intrauterine device inserted at study baseline and maintained through the active treatment and follow-up periods, providing continuous local progestin delivery to the endometrium in combination with systemic semaglutide.
A structured, protocol-defined weight loss program combining dietary counseling and physical activity guidance, delivered concurrently with pharmacologic and device-based treatment to support metabolic response, distinct from weight loss achieved through semaglutide alone.
Pathological Response Rate
Pathological Response Rate (PRR) defined as the rate of regression of atypical hyperplasia or carcinoma on histopathological examination of the 6-month (end-of-treatment) hysteroscopic sample
Time frame: 6 months
Time to response
Time to response in months from treatment initiation to first documented histopathological regression
Time frame: 12 months
Adverse events
Incidence and severity of adverse events, graded per NCI-CTCAE v5.0, including drug-related (semaglutide) and device-related (LNG-IUD) events
Time frame: 12 months
Durable response rate
The proportion of participants who achieve a complete pathological response and maintain that response, without evidence of disease recurrence or progression, through 12 months following treatment initiation. Durable response will be assessed via hysteroscopy with endometrial sampling.
Time frame: 12 months
Disease progression rate
The proportion of participants who experience disease progression, defined as an increase in histologic grade or stage of endometrial atypical hyperplasia or endometrial cancer, without ever achieving a complete pathological response, assessed through 12 months from treatment initiation. Disease status will be assessed via hysteroscopy with endometrial sampling.
Time frame: 12 months
Recurrence rate
The proportion of participants who experience recurrence of endometrial atypical hyperplasia or endometrial cancer following an initial complete pathological response, assessed through 12 months from treatment initiation. Disease status will be assessed via hysteroscopy with endometrial sampling.
Time frame: 12 months
Body weight change
Change in body weight, measured in kilograms, from baseline to 6 and 12 months following treatment initiation.
Time frame: 12 months
Body mass index (BMI) change
Change in body mass index (BMI), reported as weight in kilograms divided by height in meters squared (kg/m2) \[normal values: 18.5-24.9 kg/m2\], from baseline to 6 and 12 months following treatment initiation.
Time frame: 12 months
Waist circumference change
Change in waist circumference, measured in centimeters, from baseline to 6 and 12 months following treatment initiation.
Time frame: 12 months
Hip circumference change
Change in hip circumference, measured in centimeters, from baseline to 6 and 12 months following treatment initiation.
Time frame: 12 months
Waist-to-hip ratio change
Change in waist-to-hip ratio, calculated as waist circumference divided by hip circumference, from baseline to 6 and 12 months following treatment initiation.
Time frame: 12 months
Glycated Hemoglobin change
Change in glycated hemoglobin (HbA1c), measured as a percentage, from baseline to 6 and 12 months following treatment initiation.
Time frame: 12 months
Weight-Related Quality of Life (WRQOL)
Change in weight-related quality of life, assessed using a validated questionnaire, from baseline to 6 and 12 months following treatment initiation. We will utilize the Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQOL-Lite-CT) questionnaire. The IWQOL-Lite-CT is a 20-item patient-reported questionnaire that measures weight-related quality of life over the past 7 days. Each item is answered on a 5-point scale. It yields a total score and three composite scores: Physical (7 items), Physical Function (5 items, a subset of Physical), and Psychosocial (13 items). All scores are transformed to a 0-100 scale. Higher scores indicate better weight-related quality of life; lower scores indicate worse quality of life.
Time frame: 12 months
Health-Related Quality of Life
Change in health-related quality of life, assessed using a validated Health-Related Quality of Life questionnaire, from baseline to 6 and 12 months following treatment initiation. Health-related quality of life will be assessed with the EORTC QLQ-C30 (30 items) and its endometrial cancer-specific module, the QLQ-EN24 (24 items). The QLQ-C30 includes a global health status/quality of life scale, five functional scales (physical, role, emotional, cognitive, social), and symptom scales and items such as fatigue, pain, and nausea. The QLQ-EN24 assesses endometrial cancer-related symptoms (e.g., lymphoedema, urological, gastrointestinal, sexual/vaginal) and sexual functioning. All scores are linearly transformed to a 0-100 scale. For global health status and functional scales, higher scores indicate better quality of life and functioning. For symptom scales and items, higher scores indicate greater symptom burden, which means worse outcomes.
Time frame: 12 months
Plan to share: Yes — De-identified individual participant data, including the study protocol and statistical analysis plan, will be made available to researchers who provide a methodologically sound proposal, beginning 12 months after publication of the primary results and ending 36 months after publication. Data will be shared for the purpose of achieving the aims outlined in the approved proposal, following execution of a data access agreement.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Clinical study report
Time frame: Data will become available beginning 12 months after publication of the primary study results and will remain available for 36 months thereafter.
Access criteria: De-identified individual participant data, including the study protocol, statistical analysis plan, and informed consent form, will be available to researchers who provide a scientifically sound proposal for data use. Requests should be directed to the principal investigator. Proposals will be reviewed to confirm that the intended use is consistent with the original trial objectives and applicable data protection regulations. Approved requesters will be required to sign a data access agreement prior to receiving data. Access will be granted for the purpose of achieving the aims outlined in the approved proposal.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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Studies of the drug tested here: Semaglutide
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