Uterine Preservation Via Lifestyle Transformation

UPLifT-Endo: Uterine Preservation Via Lifestyle Transformation A Behavioral Intervention to Promote Primary Prevention and Uterine Preservation in Premenopausal Women With Obesity and Atypical Endometrial Hyperplasia or Grade 1 Endometrial Cancer

Up to 60% of endometrial cancer cases are attributed to obesity, in part because obesity promotes development of atypical endometrial hyperplasia (AEH), and up to 40% of women with AEH go on to develop endometrial cancer. The increasing prevalence of obesity in premenopausal women has resulted in increasing rates of AEH in this age group. Hysterectomy with removal of the fallopian tubes and ovaries is 100% effective in preventing endometrial cancer, but this approach results in infertility. Fertility-sparing treatments exist, such as treatment with oral or intrauterine progestin, but these treatments do not work uniformly and do not combat the underlying cause of endometrial cancer, which is obesity and metabolic syndrome. Additionally, up to 41% of women on progestin eventually experience relapse of AEH or endometrial cancer. Third, many patients have insulin resistance that may worsen with progestin therapy. Thus, to improve treatment of AEH and grade 1 endometrial cancer, prevent and reverse endometrial cancer, and allow women to preserve their fertility, the investigators must integrate an effective weight loss strategy to be given with progestin treatment. It is the hypothesis that premenopausal women with AEH desire uterine preservation will be more likely to have atypia-free uterine preservation at one year if they receive progestin in combination with a behavioral weight loss intervention versus progestin plus enhanced usual care.

Study Overview

• Status: Recruiting
• Conditions: Endometrial Hyperplasia; Grade 1 Endometrial Cancer
• Intervention / Treatment: Drug: Progestin; Drug: Levonorgestrel-releasing IUD.; Behavioral: Enhanced usual care; Behavioral: Telemedicine behavioral weight intervention

• Study Type: Interventional
• Enrollment (Estimated): 96
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Andrea R Hagemann, M.D., MSCI; Phone Number: 314-362-1763; Email: hagemanna@wustl.edu

Study Locations

• United States
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine
      • Sub-Investigator: Graham Colditz, M.D., DrPH
      • Contact: Andrea R Hagemann, M.D., MSCI; Phone Number: 314-362-1763; Email: hagemanna@wustl.edu
      • Principal Investigator: Andrea R Hagemann, M.D., MSCI
      • Sub-Investigator: Ian Hagemann, M.D., Ph.D.
      • Sub-Investigator: Esther Lu, Ph.D.
      • Sub-Investigator: David Mutch, M.D.
      • Sub-Investigator: Gary Patii, Ph.D.
      • Sub-Investigator: David Morris, Ph.D.
      • Sub-Investigator: Veronica Davé, Ph.D.
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • Recruiting
      • University of New Mexico
      • Contact: Carolyn Muller, M.D.; Phone Number: 505-272-2111
      • Principal Investigator: Carolyn Muller, M.D.
      • Sub-Investigator: Kimberly Leslie, M.D.
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Recruiting
      • University of Oklahoma
      • Contact: Kathleen Moore, M.D., MS; Phone Number: 405-271-8707
      • Principal Investigator: Kathleen Moore, M.D., MS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of histologically confirmed complex atypical endometrial hyperplasia (AEH) or grade 1 endometrial cancer.

  • Patients with a previous diagnosis of AEH or grade 1 endometrial cancer who are already being followed with conservative management with oral or LNG-IUD progestin therapy are eligible.
  • For patients with a previous diagnosis of AEH or grade 1 endometrial cancer who have been placed on progestin prior to study entry, the duration of IUD or oral progestin use prior to trial entry should be documented.
• Premenopausal woman with a uterus.
• ECOG performance status of 0-2.
• At least 18 years of age and no more than 45 years of age.
• Undergoing uterine-sparing management (e.g. due to interest in fertility preservation, interest in uterine preservation, provider recommendation, or other reason).
• BMI ≥ 30 kg/m^2.
• Prior or current receipt of progestin is allowed as above. Willingness to undergo placement of LNG-IUD at the time of study entry.
• Ability to understand and willingness to sign an IRB approved written informed consent document.

Exclusion Criteria:

• Current, active treatment for any malignant neoplasm with chemotherapy or radiation.
• Pregnant and/or breastfeeding. Participants must have a negative urine or serum pregnancy test during screening window and within 7 days prior to LNG-IUD insertion. If LNG-IUD is in place, lack of pregnancy is assumed.
• Active pelvic infection at the time of IUD placement or other contraindication to the use of an IUD in the opinion of the treating physician.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: Levonorgestrel-releasing IUD (LNG-IUD) + Behavioral Weight Loss Intervention; The levonorgestrel-releasing IUD is used in this study as per standard care.; The behavioral weight loss intervention consists of a telemedicine cognitive behavioral coaching program. At each session, patients will self-report weight, number of days they kept a food journal during the past week, average daily caloric intake for the week, number of days exercised for the week, total number of minutes of moderate physical activity, and average number of steps per day for the week.	Drug: Progestin; Released via the levonorgestrel-releasing IUD.; Drug: Levonorgestrel-releasing IUD.; Standard of care; Behavioral: Telemedicine behavioral weight intervention; Weekly telephone calls during the first month, biweekly during the next 5 months, and then monthly for the last 7 months (12 months total). Each telephone session will be 30 minutes long.
Active Comparator: Arm 2: Levonorgestrel-releasing IUD (LNG-IUD) + Enhanced Usual Care; The levonorgestrel-releasing IUD is used in this study as per standard care.; Participants will be provided with 1- to 3-page handouts on topics including healthy eating, exercise, and behavioral eating strategies from materials provided on the American Cancer Society, Society of Gynecologic Oncology, and WebMD Nourish websites. These materials encourage weight loss through calorie counting, recording dietary intake, engaging in exercise programs, and using portion control strategies.; The participants randomized to this arm will cross over to the behavioral weight loss intervention arm at 12 months if they have not achieved resolution of AEH or grade 1 endometrial cancer.	Drug: Levonorgestrel-releasing IUD.; Standard of care; Behavioral: Enhanced usual care; 1-3 page handouts

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants with atypical endometrial hyperplasia (AEH)-free biopsy	At 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to resolution of atypical endometrial hyperplasia (AEH)	Defined as the period of time in months/days from the first biopsy to show AEH or grade 1 endometrial cancer to the first biopsy that shows no evidence of hyperplasia or malignancy	Through completion of follow-up (estimated to be 2 years)
Time to resolution of endometrial cancer		Through completion of follow-up (estimated to be 2 years)
Atypia-free survival	-Defined as the time interval from the date of positive treatment response (as determined by biopsy) to the date of atypical endometrial hyperplasia (AEH) recurrence. AEH-free or the patients with lost to follow-up will be censored at the last follow-up.	Through completion of follow-up (estimated to be 2 years)
Endometrial cancer progression-free survival (EC-PFS)	EC-PFS is defined as the time interval from the date of positive treatment response (as determined by biopsy) to the date of recurrence of EC. Endometrial cancer-free patients or the patients with lost to follow-up will be censored at the last follow-up.	Through completion of follow-up (estimated to be 2 years)
Change in weight		Through completion of follow-up (estimated to be 2 years)
Change in Cancer Worry Impact 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, 6 months, 12 months, end of intervention, and 24 months (estimated to be 2 years)

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Andrea R Hagemann, M.D., MSCI, Washington University School of Medicine

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): October 24, 2024
• Primary Completion (Estimated): October 31, 2028
• Study Completion (Estimated): October 31, 2029

Study Registration Dates

• First Submitted: May 24, 2023
• First Submitted That Met QC Criteria: June 5, 2023
• First Posted (Actual): June 15, 2023

Study Record Updates

• Last Update Posted (Actual): January 20, 2026
• Last Update Submitted That Met QC Criteria: January 16, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: behavioral intervention; obesity; endometrial cancer; weight management; fertility-sparing; premenopausal endometrial hyperplasia; premenopausal endometrial cancer
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Nutrition Disorders; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Overnutrition; Body Weight; Uterine Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Overweight; Uterine Neoplasms; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Endometrial Neoplasms; Endometrial Hyperplasia; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pharmacologic Actions; Chemical Actions and Uses; Progestins
• Other Study ID Numbers: 202307204; P50CA265793 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No