Lung DiseasesNCT00037778
Genetic Modifiers of Cystic Fibrosis: Sibling Study
An observational study of Lung Diseases and Cystic Fibrosis, run by Johns Hopkins University at 1 site in United States.
Trial summary
The purpose of this study is to identify modifier genes in cystic fibrosis (CF). Read more about this study
- Who is it for?
- Ages Up to 100 years
- Conditions the study is for
- Lung Diseases, Cystic Fibrosis
- How many people
- 3,459 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2001to Feb 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 Up to 100 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Siblings with cystic fibrosis
Who may be able to join
- Diagnosis of CF
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
About this study
The purpose of this study is to identify modifier genes in cystic fibrosis (CF).
Read the detailed description
BACKGROUND:
CF is a highly variable but inevitably fatal single gene disorder. Several lines of evidence suggest that genetic background contributes to the variability of cystic fibrosis phenotypes. The study will develop CF as a model for the identification of modifier genes by capitalizing on the availability of a large motivated population of affected twins and siblings.
The study is in response to a Request for Applications titled "Genetic Modifiers of Single Gene Defect Diseases" released in August 2000 and co-sponsored by the National Institute of Diabetes, Digestive, and Kidney Diseases.
DESIGN NARRATIVE:
The study has four aims: 1. To identify heritable CF phenotypes by twin study. Intrapair and interpair variance will be determined for selected CF phenotypes, and interclass correlations (monozygotic versus dizygotic) will be performed to identify CF phenotypes with a substantial heritable component. 2. To determine the contribution of genetic and other factors to the variability of CF phenotypes by analysis of affected sibs. Variance component methods will be used to evaluate the CF phenotypes that appear to be heritable based upon other studies or the results of aim 1. 3. To identify biologic phenotypes that correlate with heritable CF phenotypes by clinical study of twins and sibs. Multivariate analysis will be used to find biologic phenotypes associated with CF phenotypes. 4. To identify modifier genes and loci responsible for heritable CF phenotypes by linkage approaches. Identity by descent and transmission disequilibrium methods will be used to test linkage between candidate genes/loci and heritable CF phenotypes. To identify novel loci, genome-wide scans will be performed upon sib pairs selected for extreme concordance or discordance for heritable traits.
- Conditions
- Lung Diseases, Cystic Fibrosis
- Medical subject headings
- Lung Diseases, Cystic Fibrosis
What is being measured
The primary outcome is the main question the study is designed to answer.
Variation among genes in siblings with cystic fibrosis as assessed by DNA
Measured: Single collection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 May 2002 (estimated)
- Study startSep 2001
- Primary completionFeb 2013
- Study completionFeb 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Lung DiseasesStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe 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
- Retrospective
- Enrolment
- 3,459 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor
- Investigators
- Garry Cutting, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00037778
- Sponsor's protocol ID
- 1178
- Other IDs
- R01HL068927
- Status last verified
- Aug 2016
- First submitted
- 20 May 2002
- Last updated
- 31 Aug 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
McWilliams R, Hoover-Fong J, Hamosh A, Beck S, Beaty T, Cutting G. Problematic variation in local institutional review of a multicenter genetic epidemiology study. JAMA. 2003 Jul 16;290(3):360-6. doi: 10.1001/jama.290.3.360.
PubMed 12865377Groman JD, Hefferon TW, Casals T, Bassas L, Estivill X, Des Georges M, Guittard C, Koudova M, Fallin MD, Nemeth K, Fekete G, Kadasi L, Friedman K, Schwarz M, Bombieri C, Pignatti PF, Kanavakis E, Tzetis M, Schwartz M, Novelli G, D'Apice MR, Sobczynska-Tomaszewska A, Bal J, Stuhrmann M, Macek M Jr, Claustres M, Cutting GR. Variation in a repeat sequence determines whether a common variant of the cystic fibrosis transmembrane conductance regulator gene is pathogenic or benign. Am J Hum Genet. 2004 Jan;74(1):176-9. doi: 10.1086/381001. Epub 2003 Dec 18.
PubMed 14685937Boyle MP. Nonclassic cystic fibrosis and CFTR-related diseases. Curr Opin Pulm Med. 2003 Nov;9(6):498-503. doi: 10.1097/00063198-200311000-00009.
PubMed 14534402Hefferon TW, Groman JD, Yurk CE, Cutting GR. A variable dinucleotide repeat in the CFTR gene contributes to phenotype diversity by forming RNA secondary structures that alter splicing. Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3504-9. doi: 10.1073/pnas.0400182101. Epub 2004 Mar 1.
PubMed 14993601
Study at a glance
From the registry record, last updated by the sponsor on 31 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genetic Modifiers of Cystic Fibrosis: Sibling Study
- ClinicalTrials.gov ID
- NCT00037778
- Acronym / sponsor ID
- 1178
- Conditions
- Lung Diseases, Cystic Fibrosis
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 3,459 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Sep 2001
- Primary completion
- Feb 2013 (actual)
- Study completion
- Feb 2013 (actual)
- First posted
- 21 May 2002 (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.
The purpose of this study is to identify modifier genes in cystic fibrosis (CF).
Detailed description
BACKGROUND:
CF is a highly variable but inevitably fatal single gene disorder. Several lines of evidence suggest that genetic background contributes to the variability of cystic fibrosis phenotypes. The study will develop CF as a model for the identification of modifier genes by capitalizing on the availability of a large motivated population of affected twins and siblings.
The study is in response to a Request for Applications titled "Genetic Modifiers of Single Gene Defect Diseases" released in August 2000 and co-sponsored by the National Institute of Diabetes, Digestive, and Kidney Diseases.
DESIGN NARRATIVE:
The study has four aims: 1. To identify heritable CF phenotypes by twin study. Intrapair and interpair variance will be determined for selected CF phenotypes, and interclass correlations (monozygotic versus dizygotic) will be performed to identify CF phenotypes with a substantial heritable component. 2. To determine the contribution of genetic and other factors to the variability of CF phenotypes by analysis of affected sibs. Variance component methods will be used to evaluate the CF phenotypes that appear to be heritable based upon other studies or the results of aim 1. 3. To identify biologic phenotypes that correlate with heritable CF phenotypes by clinical study of twins and sibs. Multivariate analysis will be used to find biologic phenotypes associated with CF phenotypes. 4. To identify modifier genes and loci responsible for heritable CF phenotypes by linkage approaches. Identity by descent and transmission disequilibrium methods will be used to test linkage between candidate genes/loci and heritable CF phenotypes. To identify novel loci, genome-wide scans will be performed upon sib pairs selected for extreme concordance or discordance for heritable traits.
Study design
- Observational model
- Family based
- Time perspective
- Retrospective
Who may qualify
- Ages
- Up to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Siblings with cystic fibrosis
Key inclusion criteria (1 listed)
- Diagnosis of CF
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
Variation among genes in siblings with cystic fibrosis as assessed by DNA
Time frame: Single collection
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 31 Aug 2016.
- Background: PubMed 12865377McWilliams R, Hoover-Fong J, Hamosh A, Beck S, Beaty T, Cutting G. Problematic variation in local institutional review of a multicenter genetic epidemiology study. JAMA. 2003 Jul 16;290(3):360-6. doi: 10.1001/jama.290.3.360.
- Background: PubMed 14685937Groman JD, Hefferon TW, Casals T, Bassas L, Estivill X, Des Georges M, Guittard C, Koudova M, Fallin MD, Nemeth K, Fekete G, Kadasi L, Friedman K, Schwarz M, Bombieri C, Pignatti PF, Kanavakis E, Tzetis M, Schwartz M, Novelli G, D'Apice MR, Sobczynska-Tomaszewska A, Bal J, Stuhrmann M, Macek M Jr, Claustres M, Cutting GR. Variation in a repeat sequence determines whether a common variant of the cystic fibrosis transmembrane conductance regulator gene is pathogenic or benign. Am J Hum Genet. 2004 Jan;74(1):176-9. doi: 10.1086/381001. Epub 2003 Dec 18.
- Background: PubMed 14534402Boyle MP. Nonclassic cystic fibrosis and CFTR-related diseases. Curr Opin Pulm Med. 2003 Nov;9(6):498-503. doi: 10.1097/00063198-200311000-00009.
- Background: PubMed 14993601Hefferon TW, Groman JD, Yurk CE, Cutting GR. A variable dinucleotide repeat in the CFTR gene contributes to phenotype diversity by forming RNA secondary structures that alter splicing. Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3504-9. doi: 10.1073/pnas.0400182101. Epub 2004 Mar 1.
Related trials for Lung Diseases
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingObservational study
A Prospective ,Multicenter ,Non-interventional ,Real-world Study Observing Changes in Molecular Markers Osimertinib Targeted Therapy in EGFRm NSCLC
Non Small Cell Lung Cancer
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingPhase 3
A Study Evaluating Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Participants With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers (CodeBreaK 202)
Non-Small Cell Lung Cancer (NSCLC)
Not yet recruitingPhase 1
Phase I Open-Label Safety Trial of Pembrolizumab for Neurological Post- Acute Sequelae of SARS-CoV-2 (PD1-PASC I)
Post-Acute COVID-19 Syndrome
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.
Garry Cutting principal investigator
Johns Hopkins University
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 Lung Diseases and Cystic Fibrosis, run by Johns Hopkins University 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 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 31 Aug 2016. 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 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?
Variation among genes in siblings with cystic fibrosis as assessed by DNA (time frame: Single collection). 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 NCT00037778, which also lists 4 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 31 Aug 2016.