Endometrial Diseases, Endometriosis, Infertility; Female, Nonimplantation, Infertility Unexplained, Uterine Diseases
Conditions
Keywords
endometriosis, SIRT1, Progesterone resistance
Brief summary
Progesterone resistance is mediated through epigenetic modification through SirT1 activation and is thought to contribute to infertility and progression of endometriosis. Endometriosis is a leading cause of unexplained IVF failure secondary to inflammatory changes that induce SirT1. The current study is designed to investigate a small molecule inhibitor of SirT1, in the clinical setting of In Vitro Fertilization and Embryo Transfer. The SAFER trial will compare EX-527 to placebo in a randomized, double-blind trial. Primary endpoints include Live Birth Rate (LBR) and secondary outcomes include pregnancy rate (PR), miscarriage rate (MR) and implantation failure rate.
Detailed description
The SAFER Trial will enroll women with unexplained failure after embryo transfer with euploid embryos. Subjects must have existing euploid embryos for transfer and test positive for SirT1 testing on endometrial biopsy. To qualify, they must be 18 to 40 years of age, have a normal uterine cavity, no serious systemic diseases (diabetes, lupus, cancer, etc) and be willing to be randomized to treatment with a SirT1 inhibitor, EX-527 or placebo. The medication will be provided and administered for 5 days prior to embryo transfer, after progesterone therapy is begun. The drug will be stopped 24 hr before embryo transfer. Standard protocols will be used including administration of progesterone, checking hCG 8 days after transfer, ultrasound monitoring of pregnancy and pregnancy outcomes recording, with Live Birth Rate (LBR) being the primary outcome of interest. We expect to enroll 30 women, with 15 subjects per arm. The goal of this study is to demonstrate efficacy for a specific inhibitor of SirT1 as a primary treatment of defects in endometrial receptivity due to endometriosis.
Interventions
DRUGEX-527 (Selisistat)
EX-527 is a specific inhibitor of the histone deacetylase Sirtuin-1 (SirT1). It is being given to reverse the effects of endometriosis, namely progesterone resistance, that is thought to interfere with the establishment of pregnancy in women with endometriosis
DRUGPlacebo
We will use the same vehicle for producing the active drug such as maltose without any hormones or active components
Sponsors
Wake Forest University Health Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Drug and placebo will be prepared in color coded capsules. Randomization will be performed using computer-generated lists assigned sequentially upon recruitment.
Intervention model description
Double blind, placebo controlled comparison of SirT1 inhibitor treatment for implantation failure associated with endometriosis
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
No
Inclusion criteria
* Must test positive for SIRT1 on mid-luteal endometrial biopsy * Prior failed embryo transfer with euploid embryos * Have at least one euploid embryo for transfer
Exclusion criteria
* systemic illness affecting kidneys or liver; chronic headache or severe migraine * Endometritis, hydrosalpinges, and known adenomyosis * Uterine septum, uterine fibroids, endometrial polyps
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Live birth rate | 9 months to 2 years | The number of successful pregnancies ending in live birth at the conclusion of the study divided by the number of embryo transfers in each group |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pregnancy rate | 9 months to 2 years | The number of subjects with a demonstrated pregnancy based on elevated and sustained hCG levels divided by the number of embryo transfers per group |
| Miscarriage rate | 9 months to 2 years | The number of sustained pregnancies lost divided by the number of pregnancies in each group |
Countries
United States
Outcome results
None listed