Inflammatory ResponseNCT04148638
Explore the Role of NLRP7 in the Regulation of Progestereone Induced Decidualization of Human Endometrial Stroma Cells
An observational study of Inflammatory Response and Abortion, Habitual, run by National Cheng-Kung University Hospital at 1 site in Taiwan.
Trial summary
The investigators have found that NLRP7 was upregulated and nuclear translocated in an in vitro model of decidualization. Knock-down or overexpression of NLRP7 reduced or enhanced the expression of decidual marker IGFBP-1. NLRP7 was also found to promote progesterone receptor (PR) activity. Read more about this study
- Who is it for?
- Ages 20 to 50 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Inflammatory Response, Abortion, Habitual
- How many people
- 204 participants
- Where
- 1 siteTaiwan
- Study dates
- Aug 2015to Jul 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 50 years
- Women only
- Healthy volunteers accepted
- Adult
Study population: It is known that NLRP7, a member of the protein family related to innate immunity, is associated with habitual abortion, and it is found that dysfunction of NLRP7 protein may affect endometrial decidualization and facilitate embryo implantation.
Who may be able to join
- Fertility woman 20-50 years-of-age -Hydatidiform Mole or Habitualabortion Exclusion Criteria:NA
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Dr. Pao-Lin Kuo (Department of Obstetrics and Gynecology)
The investigators have found that NLRP7 was upregulated and nuclear translocated in an in vitro model of decidualization. Knock-down or overexpression of NLRP7 reduced or enhanced the expression of decidual marker IGFBP-1. NLRP7 was also found to promote progesterone receptor (PR) activity. So, the investigators hypothesized that NLRP7 may regulate progesterone-induced decidualization of human endometrial stromal cells. Part I is to explore how NLRP7 is induced during the decidualization. According to the luciferase activities of NLRP7 promoter luciferase reporter systems, the region from -100 to +37 or from -1200 to -100 had positive or negative regulatory elements, respectively, in the in vitro decidualization. Part II is to explore how NLRP7 contributes the decidualization of endometrial stromal cells. By immunoprecipitations of NLRP7 or PR, the investigators found NLRP7 might involve in the transcriptional complex of PR in the in vitro decidualization. The NLRP7 interacting protein in the co-immunoprecipitations the investigatorsre analyzed by LC/MS-MS. Part III is to explore the effects of NLRP7 mutations on in vitro decidualization and macrophage differentiation.
Comparing to RFP control, the investigators found wild-type NLRP7 enhanced but NLRP7 mutants reduced IGFBP-1 expression in the in vitro decidualization. In the M1 macrophage differentiation of THP-1, wild-type and mutant NLRP7 reduced IL-1β expression compared to the RFP control. Part IV is to explore a role of MPA in macrophage differentiation. MPA drives THP-1 cells a M2-like macrophage differentiation toward a phenotype of decidual macrophages, which promoted in vitro decidualization and trophoblastic invasion, but tolerated TLR ligands stimulations. In conclusion, NLRP7 contributes in vitro decidualization of endometrial stromal cells; NLRP7 mutation may impede in vitro decidualization; NLRP7 may suppress IL-1 expression in M1 macrophage differentiation; MPA drives M2 macrophage differentiation toward a phenotype of decidual macrophage.
Read the detailed description
The investigators have found that NLRP7 was upregulated and nuclear translocated in an in vitro model of decidualization. Knock-down or overexpression of NLRP7 reduced or enhanced the expression of decidual marker IGFBP-1. NLRP7 was also found to promote progesterone receptor (PR) activity. So, the investigators hypothesized that NLRP7 may regulate progesterone-induced decidualization of human endometrial stromal cells. Part I is to explore how NLRP7 is induced during the decidualization. According to the luciferase activities of NLRP7 promoter luciferase reporter systems, the region from -100 to +37 or from -1200 to -100 had positive or negative regulatory elements, respectively, in the in vitro decidualization. Part II is to explore how NLRP7 contributes the decidualization of endometrial stromal cells. By immunoprecipitations of NLRP7 or PR, the investigators found NLRP7 might involve in the transcriptional complex of PR in the in vitro decidualization. The NLRP7 interacting protein in the co-immunoprecipitations the investigatorsre analyzed by LC/MS-MS. Part III is to explore the effects of NLRP7 mutations on in vitro decidualization and macrophage differentiation. Comparing to RFP control, the investigators found wild-type NLRP7 enhanced but NLRP7 mutants reduced IGFBP-1 expression in the in vitro decidualization. In the M1 macrophage differentiation of THP-1, wild-type and mutant NLRP7 reduced IL-1β expression compared to the RFP control. Part IV is to explore a role of MPA in macrophage differentiation. MPA drives THP-1 cells a M2-like macrophage differentiation toward a phenotype of decidual macrophages, which promoted in vitro decidualization and trophoblastic invasion, but tolerated TLR ligands stimulations. In conclusion, NLRP7 contributes in vitro decidualization of endometrial stromal cells; NLRP7 mutation may impede in vitro decidualization; NLRP7 may suppress IL-1 expression in M1 macrophage differentiation; MPA drives M2 macrophage differentiation toward a phenotype of decidual macrophage.
- Conditions
- Inflammatory Response, Abortion, Habitual
- Medical subject headings
- Abortion, Habitual
What is being measured
The primary outcome is the main question the study is designed to answer.
NLRP7 expressed in the decidualized stromal cells of the human endometrium during the first trimester.
The tissue sections of the non-pregnant endometrium (n = 5) or the first trimester endometrium (n = 5) were deparaffinized, rehydrated and stained with NLRP7 antibody. Representative images of NLRP7 immunohistochemistry in the endometrium are shown. The NLRP7 signal was developed with the anti-rabbit HRP antibody and AEC substrate. Staining with the 2nd antibody only served as the negative control. Arrows point to the endometrial stromal cells. NLRP7 dominantly appeared in the swollen decidualized stromal cells of pregnant endometrium, but not in the stromal cells of non-pregnant endometrium (magnification 200X)
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Nov 2019
- Study startAug 2015
- Primary completionJul 2018
- Study completionJul 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Inflammatory ResponseStudies of the same condition, open and under way.
- More trials run by National Cheng-Kung University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Retrospective
- Enrolment
- 204 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cheng-Kung University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Pao-Lin Kuo, MD, Principal investigator, Department of Obstetrics and Gynecology, National Cheng Kung University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04148638
- Sponsor's protocol ID
- A-ER-102-440
- Status last verified
- Nov 2019
- First submitted
- 28 Oct 2019
- Last updated
- 5 Oct 2022
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dr. Pao-Lin Kuo (Department of Obstetrics and Gynecology)
- ClinicalTrials.gov ID
- NCT04148638
- Acronym / sponsor ID
- A-ER-102-440
- Conditions
- Inflammatory Response, Abortion, Habitual
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 204 participants (actual)
- Lead sponsor
- National Cheng-Kung University HospitalUniversity, hospital or other
- Study start
- Aug 2015 (actual)
- Primary completion
- Jul 2018 (actual)
- Study completion
- Jul 2018 (actual)
- First posted
- 1 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators have found that NLRP7 was upregulated and nuclear translocated in an in vitro model of decidualization. Knock-down or overexpression of NLRP7 reduced or enhanced the expression of decidual marker IGFBP-1. NLRP7 was also found to promote progesterone receptor (PR) activity. So, the investigators hypothesized that NLRP7 may regulate progesterone-induced decidualization of human endometrial stromal cells. Part I is to explore how NLRP7 is induced during the decidualization. According to the luciferase activities of NLRP7 promoter luciferase reporter systems, the region from -100 to +37 or from -1200 to -100 had positive or negative regulatory elements, respectively, in the in vitro decidualization. Part II is to explore how NLRP7 contributes the decidualization of endometrial stromal cells. By immunoprecipitations of NLRP7 or PR, the investigators found NLRP7 might involve in the transcriptional complex of PR in the in vitro decidualization. The NLRP7 interacting protein in the co-immunoprecipitations the investigatorsre analyzed by LC/MS-MS. Part III is to explore the effects of NLRP7 mutations on in vitro decidualization and macrophage differentiation.
Comparing to RFP control, the investigators found wild-type NLRP7 enhanced but NLRP7 mutants reduced IGFBP-1 expression in the in vitro decidualization. In the M1 macrophage differentiation of THP-1, wild-type and mutant NLRP7 reduced IL-1β expression compared to the RFP control. Part IV is to explore a role of MPA in macrophage differentiation. MPA drives THP-1 cells a M2-like macrophage differentiation toward a phenotype of decidual macrophages, which promoted in vitro decidualization and trophoblastic invasion, but tolerated TLR ligands stimulations. In conclusion, NLRP7 contributes in vitro decidualization of endometrial stromal cells; NLRP7 mutation may impede in vitro decidualization; NLRP7 may suppress IL-1 expression in M1 macrophage differentiation; MPA drives M2 macrophage differentiation toward a phenotype of decidual macrophage.
Detailed description
The investigators have found that NLRP7 was upregulated and nuclear translocated in an in vitro model of decidualization. Knock-down or overexpression of NLRP7 reduced or enhanced the expression of decidual marker IGFBP-1. NLRP7 was also found to promote progesterone receptor (PR) activity. So, the investigators hypothesized that NLRP7 may regulate progesterone-induced decidualization of human endometrial stromal cells. Part I is to explore how NLRP7 is induced during the decidualization. According to the luciferase activities of NLRP7 promoter luciferase reporter systems, the region from -100 to +37 or from -1200 to -100 had positive or negative regulatory elements, respectively, in the in vitro decidualization. Part II is to explore how NLRP7 contributes the decidualization of endometrial stromal cells. By immunoprecipitations of NLRP7 or PR, the investigators found NLRP7 might involve in the transcriptional complex of PR in the in vitro decidualization. The NLRP7 interacting protein in the co-immunoprecipitations the investigatorsre analyzed by LC/MS-MS. Part III is to explore the effects of NLRP7 mutations on in vitro decidualization and macrophage differentiation. Comparing to RFP control, the investigators found wild-type NLRP7 enhanced but NLRP7 mutants reduced IGFBP-1 expression in the in vitro decidualization. In the M1 macrophage differentiation of THP-1, wild-type and mutant NLRP7 reduced IL-1β expression compared to the RFP control. Part IV is to explore a role of MPA in macrophage differentiation. MPA drives THP-1 cells a M2-like macrophage differentiation toward a phenotype of decidual macrophages, which promoted in vitro decidualization and trophoblastic invasion, but tolerated TLR ligands stimulations. In conclusion, NLRP7 contributes in vitro decidualization of endometrial stromal cells; NLRP7 mutation may impede in vitro decidualization; NLRP7 may suppress IL-1 expression in M1 macrophage differentiation; MPA drives M2 macrophage differentiation toward a phenotype of decidual macrophage.
Study design
- Observational model
- Case-control
- Time perspective
- Retrospective
Who may qualify
- Ages
- 20 to 50 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- It is known that NLRP7, a member of the protein family related to innate immunity, is associated with habitual abortion, and it is found that dysfunction of NLRP7 protein may affect endometrial decidualization and facilitate embryo implantation.
Key inclusion criteria (1 listed)
- Fertility woman 20-50 years-of-age -Hydatidiform Mole or Habitualabortion Exclusion Criteria:NA
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
NLRP7 expressed in the decidualized stromal cells of the human endometrium during the first trimester.
Time frame: 1 day
The tissue sections of the non-pregnant endometrium (n = 5) or the first trimester endometrium (n = 5) were deparaffinized, rehydrated and stained with NLRP7 antibody. Representative images of NLRP7 immunohistochemistry in the endometrium are shown. The NLRP7 signal was developed with the anti-rabbit HRP antibody and AEC substrate. Staining with the 2nd antibody only served as the negative control. Arrows point to the endometrial stromal cells. NLRP7 dominantly appeared in the swollen decidualized stromal cells of pregnant endometrium, but not in the stromal cells of non-pregnant endometrium (magnification 200X)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pao-Lin Kuo, MD principal investigator
Department of Obstetrics and Gynecology, National Cheng Kung University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Inflammatory Response and Abortion, Habitual, run by National Cheng-Kung University Hospital at 1 site in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
NLRP7 expressed in the decidualized stromal cells of the human endometrium during the first trimester. (time frame: 1 day). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2022.