Fragile X SyndromeNCT01187524
The Natural History of Reproductive and Overall Health in Girls and Women With a Pre-Mutation in the FMR1 Gene; Creation of a Patient Registry
An observational study of Fragile X Syndrome and FMR1 Premutation, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 1 site in United States.
Trial summary
Background: In human DNA, the Fragile X (FMR1) gene helps to regulate the nervous and reproductive systems. If the gene is abnormal, it can cause different kinds of problems, such as abnormal menstrual periods, decreased fertility, muscle tremors, and mental retardation. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Fragile X Syndrome, FMR1 Premutation, Primary Ovairan Insufficiency
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Aug 2010to 31 May 2013
- 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 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Women ages 18 and older
- FMR1 CGG repeats numbering between 55 and 199, as determined by standard Southern blot and PCR techniques.
Who cannot join
- Males
- Children
- Women who do not have an FMR1 pre-mutation (CGG repeat number <55 or >199)
- Inability to make personal medical decisions
- CRITERIA FOR SCREENING FOR THE FMR1 PRE-MUTATION:
- Family history of Fragile X syndrome or mental retardation
- Personal or family history of primary ovarian insufficiency (or POF or premature menopause )
- Personal or famiy history of tremor ataxia syndrome or Parkinson s disease
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: The Natural History of Reproductive and Overall Health in Women With a Pre-Mutation in the FMR1 Gene: Creation of a Patient Registry
Background:
- In human DNA, the Fragile X (FMR1) gene helps to regulate the nervous and reproductive systems. If the gene is abnormal, it can cause different kinds of problems, such as abnormal menstrual periods, decreased fertility, muscle tremors, and mental retardation. An abnormal FMR1 gene can also make a person more susceptible to other medical conditions, such as thyroid problems, high blood pressure, seizures, and depression. More research is needed on how abnormalities in the FMR1 gene can lead to these problems, and how often these problems appear in individuals with an abnormal FMR1 gene.
- Researchers are interested in developing a patient registry of women who have an abnormality in the FMR1 gene. This registry will allow researchers to follow participants over time and study possible effects of this abnormality on their general and reproductive health.
Read more
Objectives:
- To develop a patient registry of women with an abnormal FMR1 gene and monitor their general and reproductive health.
Eligibility:
- Women at least 18 years of age who have an abnormal FMR1 gene on the X chromosome.
Design:
- The following groups of women will be eligible for screening for this study:
- Those who have a family member with Fragile X Syndrome or mental retardation
- Those who have (or have a family member who has) primary ovarian insufficiency, also known as premature menopause
- Those who have (or have a family member who has) certain neurological problems such as tremors or Parkinson's disease.
- Eligible participants will be scheduled for an initial study visit at the National Institutes of Health Clinical Center. Participants who have regular menstrual periods should schedule the visit between days 3 and 8 of the menstrual cycle; those who do not have regular periods may have the visit at any time of the month. In addition, all estrogen-based treatments (such as birth control pills) must be stopped for 2 weeks prior to the study visit.
- Participants will have a full physical examination, provide a medical history, and provide blood samples for immediate and future testing. Participants will return for yearly visits for the same tests for as long as the study continues.
- Participants who have or develop primary ovarian insufficiency related to the FMR1 gene will also have tests to measure bone thickness and will have a vaginal ultrasound to examine the ovaries. These tests will be scheduled for a separate visit, and will be repeated every 5 years for the duration of the study.
Read the detailed description
Spontaneous 46,XX primary ovarian insufficiency (POI) is a cause of decreased fertility in approximately 1% of women before age 40. The most common known genetic cause of 46,XX POI is a pre -mutation in the Fragile X Mental Retardation (FMR1) gene. The FMR1 gene is located on the X-chromosome and contains a CGG repeat in the un-translated region; this CGG repeat is normally present in less than 55 copies, but has a tendency to expand across generations. Greater than 200 CGG copies results in Fragile X Syndrome (FXS), the most common form of heritable mental retardation. A pre-mutation in the FMR1 gene, defined as between 55 and 199 CGG repeats, is associated with POI in women and carries a risk of expanding to the full mutation in a woman s offspring, resulting in a child with FXS. POI that is associated with the FMR1 pre-mutation is known as Fragile X-associated POI ( FXPOI ). Approximately 20% of women with an FMR1 pre-mutation develop FXPOI. Importantly, it is not known why some women with the pre-mutation develop FXPOI and others do not. The primary objective of this study is to characterize the natural history of reproductive function in women who are FMR1 pre-mutation carriers by creating a patient registry that will allow us to follow them longitudinally. Given the relative rarity of this pre-mutation in the general population (<1%), a patient registry is necessary for enrollment of an adequate number of patients for clinically significant analyses to be performed.
In order to characterize the natural history of reproductive function in this population, we will longitudinally track reproductive health of participants, including menstrual history, pregnancy rate, and biological (serum) markers of ovarian function. The FMR1 pre-mutation may also be associated with specific general health risks, such as hypertension, thyroid disease, neurological disorders, and psychiatric disorders. A patient registry will also allow us to track development of these and other common medical conditions to determine if women with the FMR1 pre-mutation have increased health risks. Currently, there are no screening guidelines regarding reproductive or general health for women who carry the FMR1 pre-mutation, and observations from longitudinal data will help to develop such guidelines. Finally, standardized guidelines for genetic counseling of women with the FMR1 pre-mutation regarding genetic risk to their children do not exist, and data collected in this study will enable this.
- Conditions
- Fragile X Syndrome, FMR1 Premutation, Primary Ovairan Insufficiency, Premature Ovarian Failure, Premature Menopause
- Keywords
- Patient Registry, FMR1 Gene, Fragile X Syndrome, Primary Ovarian Insufficiency, Premature Ovarian Failure, Premature Ovarian Insufficiency
- Medical subject headings
- Fragile X Syndrome, Primary Ovarian Insufficiency, Menopause, Premature
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2010 (estimated)
- Study start5 Aug 2010
- Study completion31 May 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Fragile X SyndromeStudies of the same condition, open and under way.
- 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
- Time perspective
- Other
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Sponsor type
- US National Institutes of Health
- Investigators
- Lawrence M Nelson, M.D., Principal investigator, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01187524
- Sponsor's protocol ID
- 100144
- Other IDs
- 10-CH-0144
- Status last verified
- 31 May 2013
- First submitted
- 21 Aug 2010
- Last updated
- 6 Oct 2017
- Results posted
- No
Publications
Nelson LM. Clinical practice. Primary ovarian insufficiency. N Engl J Med. 2009 Feb 5;360(6):606-14. doi: 10.1056/NEJMcp0808697.
PubMed 19196677Hagerman RJ, Hagerman PJ. The fragile X premutation: into the phenotypic fold. Curr Opin Genet Dev. 2002 Jun;12(3):278-83. doi: 10.1016/s0959-437x(02)00299-x.
PubMed 12076670Wittenberger MD, Hagerman RJ, Sherman SL, McConkie-Rosell A, Welt CK, Rebar RW, Corrigan EC, Simpson JL, Nelson LM. The FMR1 premutation and reproduction. Fertil Steril. 2007 Mar;87(3):456-65. doi: 10.1016/j.fertnstert.2006.09.004. Epub 2006 Oct 30.
PubMed 17074338
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Natural History of Reproductive and Overall Health in Women With a Pre-Mutation in the FMR1 Gene: Creation of a Patient Registry
- ClinicalTrials.gov ID
- NCT01187524
- Acronym / sponsor ID
- 100144
- Conditions
- Fragile X Syndrome, FMR1 Premutation, Primary Ovairan Insufficiency, Premature Ovarian Failure, Premature Menopause
- Keywords
- Patient Registry, FMR1 Gene, Fragile X Syndrome, Primary Ovarian Insufficiency, Premature Ovarian Failure, Premature Ovarian Insufficiency
- Study type
- Observational
- Recruitment status
- Terminated
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)US National Institutes of Health
- Study start
- 5 Aug 2010
- Study completion
- 31 May 2013
- First posted
- 24 Aug 2010 (estimated)
- 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.
Background:
- In human DNA, the Fragile X (FMR1) gene helps to regulate the nervous and reproductive systems. If the gene is abnormal, it can cause different kinds of problems, such as abnormal menstrual periods, decreased fertility, muscle tremors, and mental retardation. An abnormal FMR1 gene can also make a person more susceptible to other medical conditions, such as thyroid problems, high blood pressure, seizures, and depression. More research is needed on how abnormalities in the FMR1 gene can lead to these problems, and how often these problems appear in individuals with an abnormal FMR1 gene.
- Researchers are interested in developing a patient registry of women who have an abnormality in the FMR1 gene. This registry will allow researchers to follow participants over time and study possible effects of this abnormality on their general and reproductive health.
Objectives:
- To develop a patient registry of women with an abnormal FMR1 gene and monitor their general and reproductive health.
Eligibility:
- Women at least 18 years of age who have an abnormal FMR1 gene on the X chromosome.
Design:
- The following groups of women will be eligible for screening for this study:
- Those who have a family member with Fragile X Syndrome or mental retardation
- Those who have (or have a family member who has) primary ovarian insufficiency, also known as premature menopause
- Those who have (or have a family member who has) certain neurological problems such as tremors or Parkinson's disease.
- Eligible participants will be scheduled for an initial study visit at the National Institutes of Health Clinical Center. Participants who have regular menstrual periods should schedule the visit between days 3 and 8 of the menstrual cycle; those who do not have regular periods may have the visit at any time of the month. In addition, all estrogen-based treatments (such as birth control pills) must be stopped for 2 weeks prior to the study visit.
- Participants will have a full physical examination, provide a medical history, and provide blood samples for immediate and future testing. Participants will return for yearly visits for the same tests for as long as the study continues.
- Participants who have or develop primary ovarian insufficiency related to the FMR1 gene will also have tests to measure bone thickness and will have a vaginal ultrasound to examine the ovaries. These tests will be scheduled for a separate visit, and will be repeated every 5 years for the duration of the study.
Detailed description
Spontaneous 46,XX primary ovarian insufficiency (POI) is a cause of decreased fertility in approximately 1% of women before age 40. The most common known genetic cause of 46,XX POI is a pre -mutation in the Fragile X Mental Retardation (FMR1) gene. The FMR1 gene is located on the X-chromosome and contains a CGG repeat in the un-translated region; this CGG repeat is normally present in less than 55 copies, but has a tendency to expand across generations. Greater than 200 CGG copies results in Fragile X Syndrome (FXS), the most common form of heritable mental retardation. A pre-mutation in the FMR1 gene, defined as between 55 and 199 CGG repeats, is associated with POI in women and carries a risk of expanding to the full mutation in a woman s offspring, resulting in a child with FXS. POI that is associated with the FMR1 pre-mutation is known as Fragile X-associated POI ( FXPOI ). Approximately 20% of women with an FMR1 pre-mutation develop FXPOI. Importantly, it is not known why some women with the pre-mutation develop FXPOI and others do not. The primary objective of this study is to characterize the natural history of reproductive function in women who are FMR1 pre-mutation carriers by creating a patient registry that will allow us to follow them longitudinally. Given the relative rarity of this pre-mutation in the general population (<1%), a patient registry is necessary for enrollment of an adequate number of patients for clinically significant analyses to be performed.
In order to characterize the natural history of reproductive function in this population, we will longitudinally track reproductive health of participants, including menstrual history, pregnancy rate, and biological (serum) markers of ovarian function. The FMR1 pre-mutation may also be associated with specific general health risks, such as hypertension, thyroid disease, neurological disorders, and psychiatric disorders. A patient registry will also allow us to track development of these and other common medical conditions to determine if women with the FMR1 pre-mutation have increased health risks. Currently, there are no screening guidelines regarding reproductive or general health for women who carry the FMR1 pre-mutation, and observations from longitudinal data will help to develop such guidelines. Finally, standardized guidelines for genetic counseling of women with the FMR1 pre-mutation regarding genetic risk to their children do not exist, and data collected in this study will enable this.
Study design
- Time perspective
- Other
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
Key exclusion criteria (8 listed)
- Males
- Children
- Women who do not have an FMR1 pre-mutation (CGG repeat number <55 or >199)
- Inability to make personal medical decisions
- Family history of Fragile X syndrome or mental retardation
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
Not reported in the source record.
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2017.
- Background: PubMed 19196677Nelson LM. Clinical practice. Primary ovarian insufficiency. N Engl J Med. 2009 Feb 5;360(6):606-14. doi: 10.1056/NEJMcp0808697.
- Background: PubMed 12076670Hagerman RJ, Hagerman PJ. The fragile X premutation: into the phenotypic fold. Curr Opin Genet Dev. 2002 Jun;12(3):278-83. doi: 10.1016/s0959-437x(02)00299-x.
- Background: PubMed 17074338Wittenberger MD, Hagerman RJ, Sherman SL, McConkie-Rosell A, Welt CK, Rebar RW, Corrigan EC, Simpson JL, Nelson LM. The FMR1 premutation and reproduction. Fertil Steril. 2007 Mar;87(3):456-65. doi: 10.1016/j.fertnstert.2006.09.004. Epub 2006 Oct 30.
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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.
Lawrence M Nelson, M.D. principal investigator
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
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 Fragile X Syndrome and FMR1 Premutation, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 1 site in United States.
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 2 inclusion and 8 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: stopped early, as of the sponsor's last update on 6 Oct 2017. 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 United States. 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 was stopped early. Results are not available in the source record.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01187524, which also lists 3 linked publications.
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 6 Oct 2017.