Pentalogy of CantrellNCT00083499
Mutations in Genes Associated With Pentalogy of Cantrell
An observational study of Pentalogy of Cantrell, run by National Heart, Lung, and Blood Institute (NHLBI) at 2 sites in United States.
Trial summary
This study will collect blood, urine, and other tissue samples from patients with Pentalogy of Cantrell (POC) and other inherited diseases that may involve mutations in non-muscle myosin II-B heavy chain (MYH10). We will also collect samples from the relatives of affected individuals. Read more about this study
- Who is it for?
- Ages Up to 100 years
- Conditions the study is for
- Pentalogy of Cantrell
- How many people
- 59 participants
- Where
- 2 sitesUnited States
- Study dates
- 15 Sep 2004to 6 Sep 2019
- 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 Up to 100 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Primary clinical
Who may be able to join
- Index Cases
- Those patients who have a diagnosis of POC or other related syndromes (as defined under Study Design) confirmed by telephone discussion between the investigators and the patient s physician.
- Outside Institutions- All ages will be included
- At the Clinical Center - Those subjects that are greater than or equal to 2 years of age and older.
- Relatives of Index Cases
- We may obtain samples from family members and/or relatives of those individuals who have a diagnosis of POC or other related syndrome confirmed by telephone discussion between the investigators and the referring physician with knowledge of the index case.
Show all 13Show fewer
- Outside Institutions - All ages will be included. At the Clinical Center - Those subjects that are greater than or equal to 2 years of age and older
- Fetal tissue:
- We may obtain samples from patients with a fetal diagnosis of POC or other related syndrome with diagnosis confirmed by telephone discussion between the investigators and the referring physician.
- Research use of the fetal tissue in accordance to NIH Division of Intramural Research (DIR) Program fetal tissue policy guidelines:
- No profits will be involved;
- NIH researchers will have no involvement in the termination of pregnancy, and
- The tissue must be obtained in accordance with Federal, state, and local law including those that govern basic research using human fetal tissue and research involving the transplantation of fetal tissue.
Who cannot join
- Subjects seen at the Clinical Center - Those subjects that are less than or equal to 2 years of age and older.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
Baylor College of Medicine
Houston, Texas, 77030
About this study
This study will collect blood, urine, and other tissue samples from patients with Pentalogy of Cantrell (POC) and other inherited diseases that may involve mutations in non-muscle myosin II-B heavy chain (MYH10). We will also collect samples from the relatives of affected individuals. POC is a very rare disorder in which patients have a combination of severe defects of the middle of the chest including the sternum (breastbone), diaphragm, heart, and abdominal wall. The defect are apparent before birth or at birth.
Participants may undergo a medical evaluation that could include a medical history routine blood tests, urine collection, chest x-ray, and electrocardiogram. In addition, blood, urine, saliva, buccal swab or tissue samples may be collected for protein and gene studies. The blood is drawn through a very small needle placed in an arm vein. Children may choose to have a buccal (cheek) sample taken instead of blood draw. Buccal samples can be collected by a cheek swab, in which a soft brush is rubbed on the inside lining of the mouth, or by having the child hold a tablespoon of mouthwash in his or her mouth for a full minute and then spit the mouthwash into a container. In addition, tissue samples may be collected from patients if they undergoing any surgical procedures that may be required as part of their general medical care.
Read more
Some of the cells obtained from patients or their relatives may be used to establish cell lines (a living tissue sample) that can be grown in the laboratory and used for experiments.
...
Read the detailed description
The purpose of this multisite protocol is to collect protein, DNA, and RNA from blood, sputum, urine and/or tissue samples from patients with the diagnosis of Pentalogy of Cantrell (POC) or other related syndromes in order to identify possible causative genes. We will use whole exome/genome sequencing of probands, their parents, and, if available, the affected relatives of probands to look for any exomic/genomic mutations that could be associated with this syndrome. We have produced a mouse model with the mutant mice exhibiting problems with ventral wall closure including extrathoracic location of the heart (ectopia cordis), and defects in the abdominal wall with protrusion of the guts and liver. The mice, which have a single amino acid substitution in nonmuslce myosin II-B, have severe defects in both the heart and brain, and resemble humans born with POC, who manifest these same abnormalities.
- Conditions
- Pentalogy of Cantrell
- Keywords
- Nonmuscle myosin IIB, Nonmuscle myosin IIA, Pentology of Cantrell, thoracoabdominal syndrdome, Nonmuscle Myosin IIC, Pentalogy of Cantrell, Non-muscle Myosin Heavy Chain Genes
- Medical subject headings
- Pentalogy of Cantrell, MYH9-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Index cases | |
| Group 2 | Relatives of Index Cases | |
| Group 3 | Fetal tissue |
What is being measured
The primary outcome is the main question the study is designed to answer.
Identify the gene(s) mutation (s) that causes Pentalogy of Cantrell
Identification of novel genes related to Pentalogy of Cantrell
Measured: ongoing
Secondary outcomes (2)
Since mutations in NM IIB may not be the sole cause of POC, we also intend to identify any other gene(s) mutation(s) that might be thecause of POC.
Identifying any other gene(s) mutation(s) that might be the cause of POC.
Measured: Ongoing
We may wish to procure tissues from patients with nonmuscle myosin IIA and IIC mutations in order to study the mechanism underlyingthese abnormalities.
Studying the mechanism underlying these abnormalities in procuredtissues from patients with nonmuscle myosin IIA and IIC mutations.
Measured: Ongoing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2004 (estimated)
- Study start15 Sep 2004
- Primary completion6 Sep 2019
- Study completion6 Sep 2019
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 Pentalogy of CantrellStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The 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
- Family based
- Time perspective
- Cross-sectional
- Enrolment
- 59 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Robert S Adelstein, M.D., Principal investigator, National Heart, Lung, and Blood Institute (NHLBI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00083499
- Sponsor's protocol ID
- 040202
- Other IDs
- 04-H-0202
- Status last verified
- Oct 2020
- First submitted
- 25 May 2004
- Last updated
- 8 Oct 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Ma X, Adelstein RS. In vivo studies on nonmuscle myosin II expression and function in heart development. Front Biosci (Landmark Ed). 2012 Jan 1;17(2):545-55. doi: 10.2741/3942.
PubMed 22201759Ma X, Adelstein RS. The role of vertebrate nonmuscle Myosin II in development and human disease. Bioarchitecture. 2014;4(3):88-102. doi: 10.4161/bioa.29766. Epub 2014 Aug 6.
PubMed 25098841Ma X, Adelstein RS. A point mutation in Myh10 causes major defects in heart development and body wall closure. Circ Cardiovasc Genet. 2014 Jun;7(3):257-65. doi: 10.1161/CIRCGENETICS.113.000455. Epub 2014 May 13.
PubMed 24825879
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mutations in Genes Associated With Pentalogy of Cantrell
- ClinicalTrials.gov ID
- NCT00083499
- Acronym / sponsor ID
- 040202
- Conditions
- Pentalogy of Cantrell
- Keywords
- Nonmuscle myosin IIB, Nonmuscle myosin IIA, Pentology of Cantrell, thoracoabdominal syndrdome, Nonmuscle Myosin IIC, Pentalogy of Cantrell, Non-muscle Myosin Heavy Chain Genes
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 59 participants (actual)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- 15 Sep 2004 (actual)
- Primary completion
- 6 Sep 2019 (actual)
- Study completion
- 6 Sep 2019 (actual)
- First posted
- 25 May 2004 (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.
This study will collect blood, urine, and other tissue samples from patients with Pentalogy of Cantrell (POC) and other inherited diseases that may involve mutations in non-muscle myosin II-B heavy chain (MYH10). We will also collect samples from the relatives of affected individuals. POC is a very rare disorder in which patients have a combination of severe defects of the middle of the chest including the sternum (breastbone), diaphragm, heart, and abdominal wall. The defect are apparent before birth or at birth.
Participants may undergo a medical evaluation that could include a medical history routine blood tests, urine collection, chest x-ray, and electrocardiogram. In addition, blood, urine, saliva, buccal swab or tissue samples may be collected for protein and gene studies. The blood is drawn through a very small needle placed in an arm vein. Children may choose to have a buccal (cheek) sample taken instead of blood draw. Buccal samples can be collected by a cheek swab, in which a soft brush is rubbed on the inside lining of the mouth, or by having the child hold a tablespoon of mouthwash in his or her mouth for a full minute and then spit the mouthwash into a container. In addition, tissue samples may be collected from patients if they undergoing any surgical procedures that may be required as part of their general medical care.
Some of the cells obtained from patients or their relatives may be used to establish cell lines (a living tissue sample) that can be grown in the laboratory and used for experiments.
...
Detailed description
The purpose of this multisite protocol is to collect protein, DNA, and RNA from blood, sputum, urine and/or tissue samples from patients with the diagnosis of Pentalogy of Cantrell (POC) or other related syndromes in order to identify possible causative genes. We will use whole exome/genome sequencing of probands, their parents, and, if available, the affected relatives of probands to look for any exomic/genomic mutations that could be associated with this syndrome. We have produced a mouse model with the mutant mice exhibiting problems with ventral wall closure including extrathoracic location of the heart (ectopia cordis), and defects in the abdominal wall with protrusion of the guts and liver. The mice, which have a single amino acid substitution in nonmuslce myosin II-B, have severe defects in both the heart and brain, and resemble humans born with POC, who manifest these same abnormalities.
Study design
- Observational model
- Family based
- Time perspective
- Cross-sectional
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group 1 | – | –Index cases |
| Group 2 | – | –Relatives of Index Cases |
| Group 3 | – | –Fetal tissue |
Who may qualify
- Ages
- Up to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Primary clinical
Key inclusion criteria (13 listed)
- Relatives of Index Cases
- We may obtain samples from family members and/or relatives of those individuals who have a diagnosis of POC or other related syndrome confirmed by telephone discussion between the investigators and the referring physician with knowledge of the index case.
- Outside Institutions - All ages will be included. At the Clinical Center - Those subjects that are greater than or equal to 2 years of age and older
- Fetal tissue:
- We may obtain samples from patients with a fetal diagnosis of POC or other related syndrome with diagnosis confirmed by telephone discussion between the investigators and the referring physician.
Key exclusion criteria (1 listed)
- Subjects seen at the Clinical Center - Those subjects that are less than or equal to 2 years of age and older.
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
Identify the gene(s) mutation (s) that causes Pentalogy of Cantrell
Time frame: ongoing
Identification of novel genes related to Pentalogy of Cantrell
2 secondary outcomes
Since mutations in NM IIB may not be the sole cause of POC, we also intend to identify any other gene(s) mutation(s) that might be thecause of POC.
Time frame: Ongoing
We may wish to procure tissues from patients with nonmuscle myosin IIA and IIC mutations in order to study the mechanism underlyingthese abnormalities.
Time frame: Ongoing
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 8 Oct 2020.
- Background: PubMed 22201759Ma X, Adelstein RS. In vivo studies on nonmuscle myosin II expression and function in heart development. Front Biosci (Landmark Ed). 2012 Jan 1;17(2):545-55. doi: 10.2741/3942.
- Background: PubMed 25098841Ma X, Adelstein RS. The role of vertebrate nonmuscle Myosin II in development and human disease. Bioarchitecture. 2014;4(3):88-102. doi: 10.4161/bioa.29766. Epub 2014 Aug 6.
- Background: PubMed 24825879Ma X, Adelstein RS. A point mutation in Myh10 causes major defects in heart development and body wall closure. Circ Cardiovasc Genet. 2014 Jun;7(3):257-65. doi: 10.1161/CIRCGENETICS.113.000455. Epub 2014 May 13.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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.
Robert S Adelstein, M.D. principal investigator
National Heart, Lung, and Blood Institute (NHLBI)
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Pentalogy of Cantrell, run by National Heart, Lung, and Blood Institute (NHLBI) at 2 sites 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 13 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 8 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 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?
Identify the gene(s) mutation (s) that causes Pentalogy of Cantrell (time frame: ongoing). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00083499, 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 8 Oct 2020; AzTrials last refreshed its copy on 7 Nov 2026.