Miscarriage, RecurrentNCT04141618
The Role of NLRP Gene Family (NLRP1~14) in Recurrent Miscarriage and Infertility
An observational study of Miscarriage, Recurrent and Infertility, run by National Cheng-Kung University Hospital at 1 site in Taiwan.
Trial summary
Development of mole was not associated with segregation of mutated NLRP7 allele in the haploid oocyte. We hypothesize NLRP7 is a maternal factor involved in regulating early embryo development or embryo-uterine interaction. Read more about this study
- Who is it for?
- Ages 25 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Miscarriage, Recurrent, Infertility
- How many people
- 143 participants
- Where
- 1 siteTaiwan
- Study dates
- Aug 2011to 31 Jul 2015
- 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 25 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Study population: Assuming that there are 300 cases and 300 controls enrolled, the underlying disease model is recessive, the disease prevalence is approximately 3% and the disease allele frequency is about 5%, this study has more than 80% power for detecting the SNP with an allele frequency greater than 10% and an allelic odds ratio greater than 1.4. We assumed that the SNP is either the causal gene or in LD with the causal allele and power was calculated without multiple testing corrections.
Who may be able to join
- Recurrent abortions and infertility treatments but combined with repetitive (more than two consecutive) implantation failure couples, rather than general infertility couples.
Who cannot join
- Women who do not have recurrent miscarriage and infertility problems.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Dr. Pao-Lin Kuo (Department of Obstetrics and Gynecology)
Development of mole was not associated with segregation of mutated NLRP7 allele in the haploid oocyte. We hypothesize NLRP7 is a maternal factor involved in regulating early embryo development or embryo-uterine interaction. In the proposed study, we seek to identify novel genetic variants and mutations of NLRP7 in women who experienced RM/HM. Genetic association study and haplotype analysis are performed to test assocation between NLRP7 gene and female reproductive performance. Immunohistochemical staining, RT-PCR, and Western blot analysis are used to investigate expression pattern of NLRP7 in endometrium and placenta. Two approaches are used to characterize functional significance of genetic variants/mutations. The first approach will be based on mutagenesis and the second approach will be based on induced pluripotent stem cells (iPSCs). Results obtained from the proposed study will provide novel insight into mechanism of embryo development and implantation.
Read the detailed description
Recurrent miscarriage (RM), defined as at least two consecutive fetal death or spontaneous abortions before the 20th week gestational age, occurred in about 1% to 5% couples. The causes of RM include uterine factors, endocrine factors, thromobophilic factors, immunologic factors and genetic factors. The hydatidiform mole (HM) can be divided into two separate syndromes: complete mole (CHM) and partial mole (PHM). In the West, CHMs occur in approximately 1 in every 1500 pregnancies. The incidence is higher in Latin America, Southeast Asia and the Middle East. The cause of RM and HM are not known for the vast majority of cases. The NLRP (Nucleotide-binding oligomerization domain, Leucine rich Repeat and Pyrin domain containing) family, also referred to as NALP family, is well known for its roles in apoptosis and inflammation. Expression studies showed that twelve of the fourteen members of NLRP family express differentially in human oocytes and preimplantation embryonic cells, especially NLRP7, indicating important role of NLRP family in female reproduction. Since 2006, mutations of NLRP7 have been found in women with repeated occurrence of molar pregnancy, repeated stillbirth or early spontaneous abortion. In women who experienced RM/HM, we also found some novel mutations/genetic variants of NLRP7. Taken together, these finding suggest RM and HM may share the same genetic etiology in some cases. In addition, NLRP7 is a strong candidate gene for RM/HM. A recent report showed chaotic cleavage abnormalities of embryos in patients with NLRP7 variants.
- Conditions
- Miscarriage, Recurrent, Infertility
- Keywords
- recurrent miscarriage, infertility
- Medical subject headings
- Abortion, Habitual, Infertility
What is being measured
The primary outcome is the main question the study is designed to answer.
pregnancy outcome
Pregnancy and delivery of a normal baby is defined as normal outcome
Measured: 1 month at the end of pregnancy
Secondary outcomes (1)
spontaneous abortion
fail to maintain pregnancy beyond 12 weeks
Measured: abortion before 12 weeks of gestation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2019
- Study startAug 2011
- Primary completionJul 2015
- Study completion31 Jul 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Miscarriage, RecurrentStudies 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
- Cross-sectional
- Enrolment
- 143 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
- NCT04141618
- Sponsor's protocol ID
- BR-100-006
- Status last verified
- Oct 2019
- First submitted
- 7 Apr 2014
- Last updated
- 4 Oct 2022
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 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
- NCT04141618
- Acronym / sponsor ID
- BR-100-006
- Conditions
- Miscarriage, Recurrent, Infertility
- Keywords
- recurrent miscarriage, infertility
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 143 participants (actual)
- Lead sponsor
- National Cheng-Kung University HospitalUniversity, hospital or other
- Study start
- Aug 2011
- Primary completion
- Jul 2015 (actual)
- Study completion
- 31 Jul 2015 (actual)
- First posted
- 28 Oct 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.
Development of mole was not associated with segregation of mutated NLRP7 allele in the haploid oocyte. We hypothesize NLRP7 is a maternal factor involved in regulating early embryo development or embryo-uterine interaction. In the proposed study, we seek to identify novel genetic variants and mutations of NLRP7 in women who experienced RM/HM. Genetic association study and haplotype analysis are performed to test assocation between NLRP7 gene and female reproductive performance. Immunohistochemical staining, RT-PCR, and Western blot analysis are used to investigate expression pattern of NLRP7 in endometrium and placenta. Two approaches are used to characterize functional significance of genetic variants/mutations. The first approach will be based on mutagenesis and the second approach will be based on induced pluripotent stem cells (iPSCs). Results obtained from the proposed study will provide novel insight into mechanism of embryo development and implantation.
Detailed description
Recurrent miscarriage (RM), defined as at least two consecutive fetal death or spontaneous abortions before the 20th week gestational age, occurred in about 1% to 5% couples. The causes of RM include uterine factors, endocrine factors, thromobophilic factors, immunologic factors and genetic factors. The hydatidiform mole (HM) can be divided into two separate syndromes: complete mole (CHM) and partial mole (PHM). In the West, CHMs occur in approximately 1 in every 1500 pregnancies. The incidence is higher in Latin America, Southeast Asia and the Middle East. The cause of RM and HM are not known for the vast majority of cases. The NLRP (Nucleotide-binding oligomerization domain, Leucine rich Repeat and Pyrin domain containing) family, also referred to as NALP family, is well known for its roles in apoptosis and inflammation. Expression studies showed that twelve of the fourteen members of NLRP family express differentially in human oocytes and preimplantation embryonic cells, especially NLRP7, indicating important role of NLRP family in female reproduction. Since 2006, mutations of NLRP7 have been found in women with repeated occurrence of molar pregnancy, repeated stillbirth or early spontaneous abortion. In women who experienced RM/HM, we also found some novel mutations/genetic variants of NLRP7. Taken together, these finding suggest RM and HM may share the same genetic etiology in some cases. In addition, NLRP7 is a strong candidate gene for RM/HM. A recent report showed chaotic cleavage abnormalities of embryos in patients with NLRP7 variants.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
Who may qualify
- Ages
- 25 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- Assuming that there are 300 cases and 300 controls enrolled, the underlying disease model is recessive, the disease prevalence is approximately 3% and the disease allele frequency is about 5%, this study has more than 80% power for detecting the SNP with an allele frequency greater than 10% and an allelic odds ratio greater than 1.4. We assumed that the SNP is either the causal gene or in LD with the causal allele and power was calculated without multiple testing corrections.
Key inclusion criteria (1 listed)
- Recurrent abortions and infertility treatments but combined with repetitive (more than two consecutive) implantation failure couples, rather than general infertility couples.
Key exclusion criteria (1 listed)
- Women who do not have recurrent miscarriage and infertility problems.
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
pregnancy outcome
Time frame: 1 month at the end of pregnancy
Pregnancy and delivery of a normal baby is defined as normal outcome
1 secondary outcome
spontaneous abortion
Time frame: abortion before 12 weeks of gestation
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 4 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 Miscarriage, Recurrent and Infertility, 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 1 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 4 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?
pregnancy outcome (time frame: 1 month at the end of pregnancy). 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 4 Oct 2022.