Lynch SyndromeLINEAGENCT06582914
Lynch Syndrome Integrative Epidemiology and Genetics
An observational study of Lynch Syndrome, run by University of Colorado, Denver at 2 sites in United States.
Trial summary
The vision of the "Lynch syndrome INtegrative Epidemiology And GEnetics" (LINEAGE) Consortium is to collaboratively improve the lives and longevity of individuals and families with Lynch syndrome. The mission of the LINEAGE Consortium is to collaboratively improve Lynch syndrome care through high-quality research. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lynch Syndrome
- How many people
- 5,000 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Oct 2024to 31 Dec 2054
- How long will I take part?
- 40 Years
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Individuals with Lynch Syndrome, defined as having a pathogenic or likely pathogenic variant in a mismatch repair gene (MLH1, MSH2, MSH6, PMS2, EPCAM) on germline genetic testing.
Who may be able to join
- • Adults age over 18 years
- Eligible patients must have at least one variant of uncertain significance (VUS), pathogenic or likely pathogenic variant (PV/LPV) in MLH1, MSH2, MSH6, PMS2, or EPCAM, which will be confirmed by genetic testing results (obtained as part of routine care) and a review of the variant in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/).
- Individuals who are an obligate carrier of a LS PV/LPV that is confirmed in the family.
Who cannot join
- Age under 18
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Sonia Kupfer, MD contact
United States2 sites, 2 recruiting
- Recruiting
University of Colorado
Aurora, Colorado, 80045
Sandra Boimbo, MPH, 303-724-8892, Sandra.Boimbo@cuanschutz.edu
Swati G Patel, MD, MS
- Not yet recruiting
University of Chicago
Chicago, Illinois, 60637
Ophir Gilad, 774-702-1000, ophirg@bsd.uchicago.edu
Sonia Kupfer, MD
About this study
Official title: Lynch Syndrome Integrative Epidemiology and Genetics (LINEAGE)
The vision of the "Lynch syndrome INtegrative Epidemiology And GEnetics" (LINEAGE) Consortium is to collaboratively improve the lives and longevity of individuals and families with Lynch syndrome.
The mission of the LINEAGE Consortium is to collaboratively improve Lynch syndrome care through high-quality research. This consortium will provide intellectual and infrastructure support to facilitate development of research questions, collection of standardized data and biospecimens, support of grant applications, and generation of collaborative manuscripts.
Read more
Our aims are to:
- Establish a prospective cohort of individuals with Lynch syndrome II. Collect standardized longitudinal clinical and biosample data to elucidate Lynch Syndrome epidemiology and gene-host interactions III. Promote intervention trials to improve cancer prevention and early detection in Lynch Syndrome
Read the detailed description
The main objective of this consortium is to build a shared resource to drive research in critical areas necessary to understand LS-related neoplasia risk and improve early detection and prevention of LS-associated cancers. This consortium will provide intellectual and infrastructure support to facilitate development of research questions, collection of standardized clinical data and biospecimens, support grant applications, and generate collaborative manuscripts.
Data and samples collected for LINEAGE will allow the consortium to address a variety of topic areas including but not limited to:
- Risk of prevalent and incident colorectal neoplasia among PV/LPV carriers. II. Estimate risk of prevalent and incident extra-colonic neoplasm among PV/LPV carriers.
III. Characterization of post-colonoscopy colorectal cancer among PV/LPV carriers.
IV. Risk factors for prevalent and incident neoplasia.
The LINEAGE Consortium is an observational prospective cohort study, with baseline and annual electronic health record (EHR) abstraction, and electronic participant and provider surveys. The consortium may also collect single or serial biosamples from identified and enrolled LS patients at participating centers.
- Conditions
- Lynch Syndrome
- Medical subject headings
- Colorectal Neoplasms, Hereditary Nonpolyposis
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 |
|---|---|---|
| Pateints with a germline variant in a mismatch repair gene | Individuals with germline genetic testing results showing a pathogenic, likely pathogenic or variant of uncertain significance in MLH1, MSH2, MSH6, PMS2 or EPCAM. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Colorectal cancer incidence
cases of adenocarcinoma of the colon or rectum diagnosed over the observation period
Measured: 40 years
Secondary outcomes (2)
non-colorectal cancer incidence
new cases of any cancer diagnosed over observation period
Measured: 40 years
precancerous colorectal polyps
new diagnoses of any of the following polyps in the colon or rectum
- tubular adenoma
- villous adenoma
- tubulovillous adenoma
- sessile serrated lesion
- traditional serrated adenoma
Measured: 40 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Sep 2024
- Study start1 Oct 2024
- Primary completion31 Dec 2054 (estimated)
- Study completion31 Dec 2054 (estimated)
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 Lynch SyndromeStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 5,000 participants (estimated)
- Target duration
- 40 Years
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- University of Chicago, University of Kansas, University of Pennsylvania, Johns Hopkins University, City of Hope National Medical Center, Loma Linda University, MedStar Health, University of Arizona, University of Manitoba, University of Michigan, University of North Carolina, University of Pittsburgh, University of Rochester, Dana-Farber Cancer Institute, University of Wisconsin, Madison, The Cleveland Clinic, University of California, San Diego, Kaiser Permanente, Ohio State University, Virginia Mason Hospital/Medical Center, University of Alabama at Birmingham, University of Miami
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06582914
- Sponsor's protocol ID
- 24-0163
- Acronym
- LINEAGE
- Status last verified
- Jan 2025
- First submitted
- 30 Aug 2024
- Last updated
- 15 Jan 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: We do not have IRB approval to do this at this time.
Publications
Yao MD, von Rosenvinge EC, Groden C, Mannon PJ. Multiple endoscopic biopsies in research subjects: safety results from a National Institutes of Health series. Gastrointest Endosc. 2009 Apr;69(4):906-10. doi: 10.1016/j.gie.2008.05.015. Epub 2009 Jan 10.
PubMed 19136110Kind AJH, Buckingham WR. Making Neighborhood-Disadvantage Metrics Accessible - The Neighborhood Atlas. N Engl J Med. 2018 Jun 28;378(26):2456-2458. doi: 10.1056/NEJMp1802313. No abstract available.
PubMed 29949490Dominguez-Valentin M, Sampson JR, Seppala TT, Ten Broeke SW, Plazzer JP, Nakken S, Engel C, Aretz S, Jenkins MA, Sunde L, Bernstein I, Capella G, Balaguer F, Thomas H, Evans DG, Burn J, Greenblatt M, Hovig E, de Vos Tot Nederveen Cappel WH, Sijmons RH, Bertario L, Tibiletti MG, Cavestro GM, Lindblom A, Della Valle A, Lopez-Kostner F, Gluck N, Katz LH, Heinimann K, Vaccaro CA, Buttner R, Gorgens H, Holinski-Feder E, Morak M, Holzapfel S, Huneburg R, Knebel Doeberitz MV, Loeffler M, Rahner N, Schackert HK, Steinke-Lange V, Schmiegel W, Vangala D, Pylvanainen K, Renkonen-Sinisalo L, Hopper JL, Win AK, Haile RW, Lindor NM, Gallinger S, Le Marchand L, Newcomb PA, Figueiredo JC, Thibodeau SN, Wadt K, Therkildsen C, Okkels H, Ketabi Z, Moreira L, Sanchez A, Serra-Burriel M, Pineda M, Navarro M, Blanco I, Green K, Lalloo F, Crosbie EJ, Hill J, Denton OG, Frayling IM, Rodland EA, Vasen H, Mints M, Neffa F, Esperon P, Alvarez K, Kariv R, Rosner G, Pinero TA, Gonzalez ML, Kalfayan P, Tjandra D, Winship IM, Macrae F, Moslein G, Mecklin JP, Nielsen M, Moller P. Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database. Genet Med. 2020 Jan;22(1):15-25. doi: 10.1038/s41436-019-0596-9. Epub 2019 Jul 24.
PubMed 31337882Win AK, Jenkins MA, Dowty JG, Antoniou AC, Lee A, Giles GG, Buchanan DD, Clendenning M, Rosty C, Ahnen DJ, Thibodeau SN, Casey G, Gallinger S, Le Marchand L, Haile RW, Potter JD, Zheng Y, Lindor NM, Newcomb PA, Hopper JL, MacInnis RJ. Prevalence and Penetrance of Major Genes and Polygenes for Colorectal Cancer. Cancer Epidemiol Biomarkers Prev. 2017 Mar;26(3):404-412. doi: 10.1158/1055-9965.EPI-16-0693. Epub 2016 Oct 31.
PubMed 27799157
Study at a glance
From the registry record, last updated by the sponsor on 15 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Lynch Syndrome Integrative Epidemiology and Genetics (LINEAGE)
- ClinicalTrials.gov ID
- NCT06582914
- Acronym / sponsor ID
- LINEAGE / 24-0163
- Conditions
- Lynch Syndrome
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 5,000 participants (estimated)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- University of Chicago, University of Kansas, University of Pennsylvania, Johns Hopkins University, City of Hope National Medical Center, Loma Linda University, MedStar Health, University of Arizona, University of Manitoba, University of Michigan, University of North Carolina, University of Pittsburgh, University of Rochester, Dana-Farber Cancer Institute, University of Wisconsin, Madison, The Cleveland Clinic, University of California, San Diego, Kaiser Permanente, Ohio State University, Virginia Mason Hospital/Medical Center, University of Alabama at Birmingham, University of Miami
- Study start
- 1 Oct 2024 (actual)
- Primary completion
- 31 Dec 2054 (estimated)
- Study completion
- 31 Dec 2054 (estimated)
- First posted
- 3 Sep 2024 (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 vision of the "Lynch syndrome INtegrative Epidemiology And GEnetics" (LINEAGE) Consortium is to collaboratively improve the lives and longevity of individuals and families with Lynch syndrome.
The mission of the LINEAGE Consortium is to collaboratively improve Lynch syndrome care through high-quality research. This consortium will provide intellectual and infrastructure support to facilitate development of research questions, collection of standardized data and biospecimens, support of grant applications, and generation of collaborative manuscripts.
Our aims are to:
- Establish a prospective cohort of individuals with Lynch syndrome II. Collect standardized longitudinal clinical and biosample data to elucidate Lynch Syndrome epidemiology and gene-host interactions III. Promote intervention trials to improve cancer prevention and early detection in Lynch Syndrome
Detailed description
The main objective of this consortium is to build a shared resource to drive research in critical areas necessary to understand LS-related neoplasia risk and improve early detection and prevention of LS-associated cancers. This consortium will provide intellectual and infrastructure support to facilitate development of research questions, collection of standardized clinical data and biospecimens, support grant applications, and generate collaborative manuscripts.
Data and samples collected for LINEAGE will allow the consortium to address a variety of topic areas including but not limited to:
- Risk of prevalent and incident colorectal neoplasia among PV/LPV carriers. II. Estimate risk of prevalent and incident extra-colonic neoplasm among PV/LPV carriers.
III. Characterization of post-colonoscopy colorectal cancer among PV/LPV carriers.
IV. Risk factors for prevalent and incident neoplasia.
The LINEAGE Consortium is an observational prospective cohort study, with baseline and annual electronic health record (EHR) abstraction, and electronic participant and provider surveys. The consortium may also collect single or serial biosamples from identified and enrolled LS patients at participating centers.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 40 Years
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pateints with a germline variant in a mismatch repair gene | – | –Individuals with germline genetic testing results showing a pathogenic, likely pathogenic or variant of uncertain significance in MLH1, MSH2, MSH6, PMS2 or EPCAM. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Individuals with Lynch Syndrome, defined as having a pathogenic or likely pathogenic variant in a mismatch repair gene (MLH1, MSH2, MSH6, PMS2, EPCAM) on germline genetic testing.
Key inclusion criteria (3 listed)
- • Adults age over 18 years
Key exclusion criteria (1 listed)
- Age under 18
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
Colorectal cancer incidence
Time frame: 40 years
cases of adenocarcinoma of the colon or rectum diagnosed over the observation period
2 secondary outcomes
non-colorectal cancer incidence
Time frame: 40 years
precancerous colorectal polyps
Time frame: 40 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jan 2025.
- Background: PubMed 19136110Yao MD, von Rosenvinge EC, Groden C, Mannon PJ. Multiple endoscopic biopsies in research subjects: safety results from a National Institutes of Health series. Gastrointest Endosc. 2009 Apr;69(4):906-10. doi: 10.1016/j.gie.2008.05.015. Epub 2009 Jan 10.
- Background: PubMed 29949490Kind AJH, Buckingham WR. Making Neighborhood-Disadvantage Metrics Accessible - The Neighborhood Atlas. N Engl J Med. 2018 Jun 28;378(26):2456-2458. doi: 10.1056/NEJMp1802313. No abstract available.
- Background: PubMed 31337882Dominguez-Valentin M, Sampson JR, Seppala TT, Ten Broeke SW, Plazzer JP, Nakken S, Engel C, Aretz S, Jenkins MA, Sunde L, Bernstein I, Capella G, Balaguer F, Thomas H, Evans DG, Burn J, Greenblatt M, Hovig E, de Vos Tot Nederveen Cappel WH, Sijmons RH, Bertario L, Tibiletti MG, Cavestro GM, Lindblom A, Della Valle A, Lopez-Kostner F, Gluck N, Katz LH, Heinimann K, Vaccaro CA, Buttner R, Gorgens H, Holinski-Feder E, Morak M, Holzapfel S, Huneburg R, Knebel Doeberitz MV, Loeffler M, Rahner N, Schackert HK, Steinke-Lange V, Schmiegel W, Vangala D, Pylvanainen K, Renkonen-Sinisalo L, Hopper JL, Win AK, Haile RW, Lindor NM, Gallinger S, Le Marchand L, Newcomb PA, Figueiredo JC, Thibodeau SN, Wadt K, Therkildsen C, Okkels H, Ketabi Z, Moreira L, Sanchez A, Serra-Burriel M, Pineda M, Navarro M, Blanco I, Green K, Lalloo F, Crosbie EJ, Hill J, Denton OG, Frayling IM, Rodland EA, Vasen H, Mints M, Neffa F, Esperon P, Alvarez K, Kariv R, Rosner G, Pinero TA, Gonzalez ML, Kalfayan P, Tjandra D, Winship IM, Macrae F, Moslein G, Mecklin JP, Nielsen M, Moller P. Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database. Genet Med. 2020 Jan;22(1):15-25. doi: 10.1038/s41436-019-0596-9. Epub 2019 Jul 24.
- Background: PubMed 27799157Win AK, Jenkins MA, Dowty JG, Antoniou AC, Lee A, Giles GG, Buchanan DD, Clendenning M, Rosty C, Ahnen DJ, Thibodeau SN, Casey G, Gallinger S, Le Marchand L, Haile RW, Potter JD, Zheng Y, Lindor NM, Newcomb PA, Hopper JL, MacInnis RJ. Prevalence and Penetrance of Major Genes and Polygenes for Colorectal Cancer. Cancer Epidemiol Biomarkers Prev. 2017 Mar;26(3):404-412. doi: 10.1158/1055-9965.EPI-16-0693. Epub 2016 Oct 31.
- Individual participant dataSharing planned: No. We do not have IRB approval to do this at this time.
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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.
Sonia Kupfer, MD contact
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 Lynch Syndrome, run by University of Colorado, Denver 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 3 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: looking for participants now, as of the sponsor's last update on 15 Jan 2025. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Swati G Patel, MD, MS (3032170731, swati.patel@cuanschutz.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Colorectal cancer incidence (time frame: 40 years). 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 NCT06582914, 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 15 Jan 2025.