Monogenic Diabetes Misdiagnosed as Type 1

NCT03988764 | Recruiting

• 2 other identifiers: ADDAMCanscreen
• Study Type: observational
• Target: 5,000
• Locations: 1 country
• Sites: 1

Brief Summary

The study has two aims:

1. 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. 2.To discover novel genes whose mutations cause monogenic diabetes misdiagnosed as T1D.

Conditions

Maturity-onset Diabetes in the Young (MODY); Diabetes Mellitus, Type 1; Monogenic Diabetes; Neonatal Diabetes; Wolfram Syndrome; Wolcott-Rallison Syndrome; Mitochondrial Diabetes

Outcome Measures

Primary Outcomes (2)

• Proportion of monogenic diabetes among patients diagnosed as type 1 diabetes.

  The exomes of all patients negative for four T1D autoantibodies will be sequenced and pathogenic variants in genes known to cause monogenic diabetes will be called and annotated. The frequency of genes carrying such variants among these patients will be compared to control exomes from public databases.

  6 years

• Proportion of patients carrying mutations in previously unstudied genes that meet statistical criteria of pathogenicity for monogenic diabetes.

  Exomes not found to carry a mutation (per outcome 1) will be analyzed to discover pathogenic variants in novel genes. Genes mutated in more than one unrelated probands will be statistically evaluated to see if variants in these gene occur more frequently than in control exomes. The number of probands that is needed to fulfill this criterion will depend on the gene's tolerance to protein-altering mutations.

  7 years

Secondary Outcomes (1)

• Risk-prediction score for monogenic diabetes mutation in antibody negative T1D patients

  5 years

Study Arms (2)

Antibody-negative

Patient has been found negative for at least three T1D antibodies. The investigators will proceed with whole exome sequencing

Other: None AHT

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.

Other: None AHT

Interventions

None AHT OTHER

No further intervention planned for either group as part of the current study.

Antibody-negative; Antibody-positive

Eligibility Criteria

• Age: 1 Day - 25 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Cases diagnosed as type 1 diabetes or undetermined type.

You may qualify if:

• Diagnosis of diabetes under the age of 25 as either type 1 or undetermined type.

You may not qualify if:

• Existing T1D autoantibody testing with a positive result

Sponsors & Collaborators

• McGill University Health Centre/Research Institute of the McGill University Health Centre: lead

Study Sites (1)

The Montreal Children's Hospital

Montreal, Quebec, H4A 3J1, Canada

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

serum and purified DNA.

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Wolfram Syndrome; Wolcott-Rallison syndrome

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Deaf-Blind Disorders; Deafness; Hearing Loss; Hearing Disorders; Ear Diseases; Otorhinolaryngologic Diseases; Optic Atrophies, Hereditary; Optic Atrophy; Optic Nerve Diseases; Cranial Nerve Diseases; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Sensation Disorders; Neurologic Manifestations; Blindness; Vision Disorders; Eye Diseases, Hereditary; Eye Diseases; Diabetes Insipidus; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Pituitary Diseases

Central Study Contacts

Constantin Polychronakos, MD

CONTACT

5144124400; constantin.polychronakos@mcgill.ca

Angeliki Makri, MD

CONTACT

5144124400; angeliki.makri@mcgill.ca

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior investigator

Study Record Dates

• First Submitted: June 11, 2019
• First Posted: June 17, 2019
• Study Start: September 24, 2019
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: December 10, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: 15 years
• Access Criteria: Approval, by the sponsor, of a research plan that proposes to use the data to promote diabetes research

Locations

CA (1)