Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
RECRUITING
5000 participants
OBSERVATIONAL
2019-09-24
2025-12-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
1. To (1a) determine the frequency of monogenic diabetes misdiagnosed as type 1 diabetes (T1D) and (2) to define an algorithm for case selection.
2. To discover novel genes whose mutations cause monogenic diabetes misdiagnosed as T1D.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
1. Variant annotation will be focused on known monogenic diabetes genes. Variants rated as pathogenic, likely pathogenic or of unknown significance whose zygosity fits the genetic model, will be confirmed in a clinically certified laboratory and communicated to the treating health care team. End-point is the frequency of such variants compared to their frequency in control, non-T1D exomes.
2. The following variables will be examined for the ability to predict monogenic diabetes: Negativity for all autoantibodies tested, family history, polygenic T1D risk score, age of onset, sex, glycosylated hemoglobin (HbA1c), insulin dose, and presence of syndromic features. Predictors will be analyzed by multiple regression and results subjected to jackknife (leave-one-out) validation. Machine-learning techniques may be used.
Aim 2. Variants outside known genes in non-diagnostic exomes will be annotated and examined under autosomal dominant, recessive, X-linked and mitochondrial inheritance models. Corresponding frequency cutoffs will be 0.0005, 0.01, 0.001 and 0.0005 (if heteroplasmy \>70%). Formal mutation-burden analysis will be based on depth-adjusted data from the Genome Aggregation Database (gnomAD). Genes mutated in more than one unrelated proband will be examined by a statistical approach taking into account the presence of a large number of phenocopies (Akawi et al., Nat Genet. 2015;47:1363-1369). Genes that achieve statistical significance will be tested in additional cohorts with international collaborations.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
CASE_ONLY
PROSPECTIVE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Antibody-negative
Patient has been found negative for at least three T1D antibodies.
The investigators will proceed with whole exome sequencing
None AHT
No further intervention planned for either group as part of the current study.
Antibody-positive
Patient has been found to be positive for at least one T1D autoantibody.
No further studies will be performed as part of the main study.
None AHT
No further intervention planned for either group as part of the current study.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
None AHT
No further intervention planned for either group as part of the current study.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
Exclusion Criteria
1 Day
25 Years
ALL
Yes
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
McGill University Health Centre/Research Institute of the McGill University Health Centre
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Constantin Polychronakos
Senior investigator
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
The Montreal Children's Hospital
Montreal, Quebec, Canada
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
Natalija Popovic, PhD
Role: primary
Angeliki Makri, MD
Role: backup
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
Canscreen
Identifier Type: OTHER
Identifier Source: secondary_id
ADDAM
Identifier Type: -
Identifier Source: org_study_id