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Quantitative Identification of Implantation Receptivity by Single Cell Transcriptome Analysis

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ClinicalTrials.gov Identifier: NCT03091023
Recruitment Status : Unknown
Verified March 2017 by Carlos Simon, Igenomix.
Recruitment status was:  Active, not recruiting
First Posted : March 27, 2017
Last Update Posted : March 27, 2017
Sponsor:
Collaborator:
Stanford University
Information provided by (Responsible Party):
Carlos Simon, Igenomix

Tracking Information
First Submitted Date  ICMJE August 30, 2016
First Posted Date  ICMJE March 27, 2017
Last Update Posted Date March 27, 2017
Study Start Date  ICMJE March 2016
Estimated Primary Completion Date December 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 21, 2017)
Transcriptomic profile analysis of the endometrial samples by RNA sequencing. [ Time Frame: 24 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Quantitative Identification of Implantation Receptivity by Single Cell Transcriptome Analysis
Official Title  ICMJE Non-invasive Transcriptomic Signature at the Single Cell Level in Endometrial Fluid as a Novel Diagnostic Test of Human Endometrial Receptivity
Brief Summary This project aims to study the endometrial transcriptome at the single cell level in both endometrial native tissue (biopsies) and endometrial fluid. Basically, the goals are: 1) To use the resolution provided by single-cell RNA-seq to deconvolute real time dynamics in endometrium transcriptome throughout the menstrual cycle from artifacts produced by known population heterogeneity, and 2) To use endometrium fluid to replace endometrium biopsies as signal source to develop a new diagnostic platform to determine the endometrium receptive state which is high resolution and minimally invasive. This study will provide an unprecedented high-resolution characterization of the endometrium cellular hierarchy via whole transcriptome analysis throughout the menstrual stages. These results will lead to a robust definition of stage-defining gene expression signatures and resolve the long-standing inconsistencies originating from bulk tissue studies. The dataset will be further explored via informatics tools to provide biological insights into the dynamics of endometrium and initiate new anchor points for functional studies.
Detailed Description

Successful embryo implantations for in vitro fertilization require both healthy embryos and a receptive endometrium. The window of implantation (WOI), during which endometrium reaches receptive state, varies among individuals. Displacements of WOI have been reported to be a major cause of repeated implantation failures. However, a reliable diagnostic metric to evaluate endometrial receptive status is lacking. The propose of this study is to use single-cell RNA seq and bioinformatics tools to develop a high-resolution platform to characterize endometrium activities and to measure endometrial receptive state in a non-invasive manner.

First objective is to develop an experimental pipeline to generate high quality single-cell RNA-seq data from endometrial biopsies and endometrial fluid from healthy patients throughout the menstrual cycle at each of these stages: early proliferative (EP; days 0-8), late proliferative (LP; days 9-14), early secretory (ES; days 15-18), mid-secretory or receptive (MS; days 19-23), and late secretory (LS; days 24-30). These tissues will be dissociated mechanically and enzymatically and subjected to microfluidic sorting, single cell transcriptome amplification and analysis. These data will provide the first transcriptome-wide single cell data various cell types of the human endometrium.

Secondly, this study look at establish algorithmic models to distinguish epithelial and stroma populations informatically, without the need to first purify populations of interest. This will enable transcriptome analysis from mixed populations of cells.

Finally evaluate the use of endometrial fluid as an alternative source for receptivity diagnosis analyzing the transcriptome profile of single cells from Endometrial fluid collected from human patients at different menstrual stages. These signatures will also be compared and correlated with signatures obtained from biopsies, which will help us better understand the biological events that lead to the occurrence of these cells in the endometrial fluid and evaluate the potential of extending their use for diagnosis of other endometrium conditions.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Endometrial Receptivity Diagnosis
Intervention  ICMJE Procedure: Endometrial Biopsy and endometrial fluid collection
Study Arms  ICMJE
  • Active Comparator: Natural cycle

    Endometrial biopsies and endometrial fluid obtained from healthy females throughout the menstrual cycle at each of these stages:

    Early proliferative (EP; days 0-8), late proliferative (LP; days 9-14), early secretory (ES; days 15-18), mid-secretory or receptive (MS; days 19-23), and late secretory (LS; days 24-30)

    Intervention: Procedure: Endometrial Biopsy and endometrial fluid collection
  • Active Comparator: ERA in HRT cycle
    Endometrial biopsy and endometrial fluid obtained from woman undergoing to Endometrial Receptivity Analysis (ERA) in a hormonal replacement therapy (HRT) cycle.
    Intervention: Procedure: Endometrial Biopsy and endometrial fluid collection
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: March 21, 2017)
70
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2018
Estimated Primary Completion Date December 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Healthy women in natural cycle;
  • Normal karyotype;
  • Negative serologic tests for HIV, HBV, HCV, RPR;
  • BMI: 18 - 30 Kg/m2 (both included);
  • Women with regular menstrual cycle (3-4/28-30 days).

Exclusion Criteria:

  • Patients who had carried an intrauterine device in the previous 3 months;
  • Patients who have taken hormonal contraceptives in the previous 2 months;
  • Adnexal or uterine pathologies;
  • Polycystic ovary;
  • Any unstable disease or medical condition that could interfere with the study or put in risk the health of the patient (evaluated by the principal researcher of the research team);
  • Any illness or medical unstable condition.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 35 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03091023
Other Study ID Numbers  ICMJE 1603-IGX-016-CS
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Carlos Simon, Igenomix
Study Sponsor  ICMJE Igenomix
Collaborators  ICMJE Stanford University
Investigators  ICMJE Not Provided
PRS Account Igenomix
Verification Date March 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP