Weight Management Plus Levonorgestrel Intrauterine System or Megestrol Acetate in Endometrial Atypical Hyperplasia: Multiple Single-arm, Prospective and Open-label Clinical Study
Trial Snapshot
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Enrollment
- 172
- Locations
- 1
- Primary Endpoint
- Pathological complete response (CR) rates
Study Overview
Brief Summary
To investigate the efficacy of weight management plus levonorgestrel intrauterine system (LNG-IUS) or megestrol acetate (MA) in obese patients with endometrial atypical hyperplasia (EAH) asking for conservative therapy.
Detailed Description
Background:
High-efficacy progesterone, such as levonorgestrel intrauterine system (LNG-IUS), megestrol acetate (MA), and medroxyprogesterone acetate(MPA), is the first-line treatment for women with endometrial atypical hyperplasia (EAH) who want to preserve fertility. About 70% to 80% of those patients can achieve complete remission (CR) with a median CR time of about 6 months, but about 20% to 30% of those patients get no response or need longer time to get CR (over one year or even longer).
Overweight or obesity is an independent risk factor for fertility-sparing treatment response and pregnancy outcomes in young females with EAH or early endometrioid cancer (EEC). Evidence showed that obesity can cause lower CR rates and longer time to get CR and lower birth rates in EAH or EEC patients asking for conservative therapy. Weight management has been proved to improve metabolic disorders, ovarian functions, and pregnancy outcomes. Metformin, as a diabetes drug, has been proved to increase CR rates in EAH or EEC patients treated with MA for fertility. Weight management has raised more and more attention and has been proved to benefit metabolic and pregnancy outcomes. Based on previous research and published studies, the hypothesise is that weight management plus progestin therapy may raise CR rates and pregnancy outcomes in young female EAH patients asking for fertility conservation.
Enhanced lifestyle management (diet control, exercise, and daily behavioral guidance) may improve metabolic conditions, increase CR rates and pregnancy outcomes in obese EAH patients who want to preserve fertility. Till now, no similar studies were found, so this study is designed to explore the efficacy of weight control in EAH fertility-sparing patients to provide new evidence for improving conservative treatment.
Objective:
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 45 Years (Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •1.18 years≤age≤45years 2.BMI (body mass index) ≥24kg/m2 3.Consent informed and signed 4.Pathologically confirmed as endometrial atypical hyperplasia. Patients with endometrial specimens obtained by endometrial biopsy, diagnostic curettage or hysteroscopy and diagnosed histologically as endometrial atypical hyperplasia. If specimens are from other hospitals, they must be counseled or reconfirmed by the Department of Pathology of the Obstetrics and Gynecology Hospital of Fudan University.
- •5.Have a strong desire to reproduce and ask for fertility preservation or those who insist on keeping the uterus despite no reproductive requirements.
- •6.Have good compliance and follow-up conditions, and patients are willing to follow up in Obstetrics and Gynecology Hospital of Fudan University in time.
Exclusion Criteria
- •Combined with severe medical disease or liver or kidney dysfunction: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level elevates to 3 times or more of the upper limit of normal, kidney dysfunction (creatinine clearance < 30 mL/min)
- •Patients are diagnosed with other malignant tumors of the reproductive system; patients with breast cancer or other hormone-dependent tumors that cannot be used with progesterone.
- •Those who have received high doses of high potency progestin or oral contraceptives within the last 3 months (or those on maintenance medication).
- •Those who require hysterectomy or other methods other than conservative treatment.
- •Known or suspected pregnancy.
- •Those who has contraindications to use progestin.
- •Deep vein thrombosis, stroke, myocardial infarction.
- •Severe joint lesions that prevent walking or movement.
- •untreated or recurrent pelvic inflammatory disease (PID)
- •an untreated or uncontrolled pelvic infection (vaginal, cervical, uterine);
- •Cervical dysplasia
- •Congenital or acquired uterine abnormalities, including uterine fibroid tumors or conditions that affect the shape of the uterus
- •allergic to the LNG-IUS components
- •uterine cavity is too large (average uterine diameter is over 7 cm) or have a history of LNG-IUS falling out.
- •Notes: the last 6 criteria are only applied for patients with LNG-IUS.
Arms & Interventions
overweight MA+ILI
enrolled overweight (24kg/m2≤BMI<28kg/m2) patients will receive megestrol acetate 160mg po qd plus weight management
Intervention: Megestrol Acetate 160 MG Oral Tablet (Drug)
obese MA+ILI
enrolled obese (BMI≥28kg/m2) patients will receive megestrol acetate 160mg po qd plus weight management
Intervention: Megestrol Acetate 160 MG Oral Tablet (Drug)
obese LNG-IUS+ILI
enrolled obese (BMI≥28kg/m2) patients will be treated with LNG-IUS plus weight management
Intervention: Levonorgestrel-Releasing Intrauterine Contraceptive System (Mirena), 52 Mg (Drug)
obese MA+ILI
enrolled obese (BMI≥28kg/m2) patients will receive megestrol acetate 160mg po qd plus weight management
Intervention: Intensive Lifestyle Intervention (ILI) (Behavioral)
obese LNG-IUS+ILI
enrolled obese (BMI≥28kg/m2) patients will be treated with LNG-IUS plus weight management
Intervention: Intensive Lifestyle Intervention (ILI) (Behavioral)
overweight MA+ILI
enrolled overweight (24kg/m2≤BMI<28kg/m2) patients will receive megestrol acetate 160mg po qd plus weight management
Intervention: Intensive Lifestyle Intervention (ILI) (Behavioral)
overweight LNG-IUS+ILI
enrolled overweight (24kg/m2≤BMI<28kg/m2) patients will be treated with LNG-IUS plus weight management
Intervention: Intensive Lifestyle Intervention (ILI) (Behavioral)
overweight LNG-IUS+ILI
enrolled overweight (24kg/m2≤BMI<28kg/m2) patients will be treated with LNG-IUS plus weight management
Intervention: Levonorgestrel-Releasing Intrauterine Contraceptive System (Mirena), 52 Mg (Drug)
Outcomes
Primary Outcomes
Pathological complete response (CR) rates
Time Frame: From date of recruitment until the date of CR, assessed up to 28 weeks.
The 28-week CR rates will be calculated in four arms
Secondary Outcomes
- Blood lipids change(From date of recruitment, assessed up to 28 weeks.)
- Ovarian reserve function(From date of recruitment, assessed up to 28 weeks.)
- Blood pressures change(From date of recruitment, assessed up to 28 weeks.)
- Blood glucose change(From date of recruitment, assessed up to 28 weeks.)
- Impact of Weight on Quality of Life(From date of recruitment, assessed up to 28 weeks.)
- Physical activities change(From date of recruitment, assessed up to 28 weeks.)
- Chronic inflammatory index (TNF-α) change(baseline, 3 months and 6 months after treatment.)
- Time of pathological complete response (CR)(From date of recruitment until the date of CR, assessed up to 2 years.)
- Pregnancy outcomes(up to 2 years after complete response of the last participant)
- Heart rates change(From date of recruitment, assessed up to 28 weeks.)
- Chronic inflammatory index (IL-1) change(baseline, 3 months and 6 months after treatment.)
- Weight change(From date of recruitment, assessed up to 28 weeks.)
- Body composition change(From date of recruitment, assessed up to 28 weeks.)
- Quality of life change(From date of recruitment, assessed up to 28 weeks.)
- Insulin resistance change(Baseline，3months and 6months after enrolled.)
- Chronic inflammatory index (IL-6) change(baseline, 3 months and 6 months after treatment.)
- Incidence of adverse events(From date of recruitment until the date of CR, assessed up to 2 years.)
- Relapse rates(up to 2 years after the treatment for each patient)
Investigators
Xiaojun Chen
Principal Investigator
Fudan University