A Randomized Controlled Pilot Study of Polyethylene Glycol Loxenatide Plus LNG-IUS in Women With Endometrial Atypical Hyperplasia
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Fudan University
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Pathological complete response (CR) rates
Study Overview
Brief Summary
To study if polyethylene glycol loxenatide plus levonorgestrel-releasing intrauterine system (LNG-IUS) will improve response rates in patients with endometrial atypical hyperplasia.
Detailed Description
Background: Obesity or overweight is associated with lower treatment response and longer time to achieve complete response(CR) in patients with atypical endometrial hyperplasia (AEH) who want to preserve fertility, as evidenced by our research and lots of published studies. The larger the baseline weight of AEH patients, the more the weight gains after high-dose progesterone treatment. Obese AEH patients have a lower response to high-dose progesterone.
Losing weight may help improve treatment response. Weight management and lifestyle intervention have been written into 2020 uterine NCCN (National Comprehensive Cancer Network) guidelines. Our research showed that metformin may improve insulin resistance in patients with AEH, and shorten time to achieve CR, and increase the CR rates. Theoretically, Losing weight can improve the chronic inflammatory environment in the endometrium and whole body and improve metabolic disorder which help patients achieve CR.
LNG-IUS will be adopted in this research. Though LNG-IUS and high-dose progesterone have similar efficacy in treating AEH patients, long-term treatment of progesterone has many side effects. Compared to oral progesterone, LNG-IUS has fewer side effects and fewer effects on weight gaining.
GLP-1 receptor agonist (GLP-1RA), which is one of the commonly used hypoglycemic drugs, has been approved for weight control. Loxenatide is the first Chinese-produced long-acting GLP-1R agonist. It is applicable for diabetes patients. In the USA, some GLP-1RA has been applied for losing weight, such as liraglutide and semaglutide. GLP-1RA acts through improving insulin sensitivity, decreasing glucagon secretion, inhibiting appetite, delaying gastric emptying, and improving whole-body inflammation condition. Loxenatide plus LNG-IUS may improve the efficacy of preserving fertility in obese AEH patients through help patients lose weight.
Objective: To investigate whether loxenatide plus LNG-IUS improves the efficacy of preserving fertility when compared to LNG-IUS alone in obese women with AEH who want fertility conservation.
Study Design
- Study Type
- Interventional
- Allocation
- 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
- •BMI (body mass index) ≥28kg/m2
- •Consent informed and signed
- •Pathologically confirmed as endometrial atypical hyperplasia
- •Have a strong desire to reproduce and ask for fertility preservation or those who insist on keeping the uterus despite no reproductive requirements
- •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
- •Diagnosed as type 2 diabetes
- •Diabetic ketoacidosis
- •History of acute pancreatitis
- •Have a history or family history of medullary thyroid carcinoma; multiple endocrine neoplasia syndrome type 2 (MEN2)
- •Combined with severe medical disease or severely impaired liver and kidney function
- •Patients with other types of endometrial cancer or other malignant tumors of the reproductive system; patients with breast cancer or other hormone- dependent tumors that cannot be used with progesterone
- •Those who require hysterectomy or other methods other than conservative treatment with drugs
- •Known or suspected pregnancy
- •Currently suffering from pelvic inflammatory disease or diagnosed as pelvic inflammatory disease
- •Lower reproductive system infection
- •abnormal cervical dysplasia
- •Congenital or acquired uterine abnormalities, including fibroids that deform the uterine cavity
- •Allergic to any parts of LNG-IUS components
- •The uterine cavity is too large (average diameter is over 7cm) or the history of LNG-IUS falling off
Arms & Interventions
LNG-IUS
enrolled patients will receive LNG-IUS for 6 months or longer till complete response
Intervention: levonorgestrel-releasing intrauterine system (Device)
LOX+LNG-IUS
enrolled patients will receive LNG-IUS plus polyethylene glycol loxenatide for treatment.
Intervention: levonorgestrel-releasing intrauterine system (Device)
LOX+LNG-IUS
enrolled patients will receive LNG-IUS plus polyethylene glycol loxenatide for treatment.
Intervention: Polyethylene Glycol Loxenatide (Drug)
Outcomes
Primary Outcomes
Pathological complete response (CR) rates
Time Frame: From date of randomization until the date of CR, assessed up to 32 weeks.
The 32-week CR rates will be calculated in two groups
Secondary Outcomes
- weight change(From date of randomization until the date of CR, assessed up to 32weeks.)
- changing of insulin resistance(From date of randomization until the date of CR, assessed up to 32weeks.)
- Relapse rates(up to 2 years after the treatment for each patient)
- pregnancy outcomes(up to 2 years after the treatment for each patient)
- Time of pathological complete response (CR)(From date of randomization until the date of CR, assessed up to 2 years)
- safety and side effects(From date of randomization until the date of CR, assessed up to 2 years)
- 16-week complete response (CR) rates(From date of randomization until the date of CR, assessed up to 16 weeks.)
- 28-week complete response (CR) rates(From date of randomization until the date of CR, assessed up to 28 weeks.)
Investigators
Xiaojun Chen
Principal Investigator，Clinical Professor
Fudan University