RADIANT: Rare and Atypical Diabetes Network

Sponsor

University of South Florida (Other)

Overall Status

Recruiting

CT.gov ID

NCT05544266

Collaborator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)

2,000

Enrollment

Locations

119

Anticipated Duration (Months)

142.9

Patients Per Site

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RADIANT is a network of 14 clinical sites and several laboratories dedicated to the study of atypical diabetes.

The objective of this study is to define new forms of diabetes and the unique mechanisms underlying these forms of atypical diabetes. The specific aims are to:

Identify and enroll individuals and families with undiagnosed rare and atypical forms of diabetes.
Determine the etiologic basis of the metabolic disorder among individuals and families with novel forms of rare and atypical diabetes.
Understand the pathophysiology of individuals and families with novel forms of rare and atypical forms of diabetes.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus Diabetes Mellitus Progression Glucose Intolerance Glucose Metabolism Disorders Metabolic Disease Endocrine; Complications Endocrine System Diseases

Detailed Description

RADIANT has three distinct stages.

Stage 1:

Stage 1 participants will complete a consent form and a questionnaire to determine the potential for having atypical forms of diabetes. Participants identified as potentially atypical based on questionnaire responses will be asked to provide a blood sample to test for islet autoantibodies and complete additional questionnaires.

The RADIANT Adjudication Committee, which is comprised of a team of experts in diabetes, will assess the data collected in Stage 1 and select and prioritize participants to proceed to Stage 2 and 3 for Whole Genome Sequencing (WGS) and other testing.

Stage 2:

Stage 2 of the study includes genetic screening for known forms of monogenic diabetes. Participants will consent for this stage of the study, complete a family history questionnaire, and have blood collected for DNA and RNA extraction, storage, and analysis. WGS will be performed on all DNA samples. If no pathogenic/likely pathogenic variant in a known monogenic diabetes gene that is thought to explain the participant's diabetes is identified by WGS, RNA Sequencing will be performed at Baylor College of Medicine.

Stage 3:

Stage 3 of the study includes deeper phenotyping. All participants who proceed to Stage 3 will visit a study clinic to consent and complete Stage 3 Standard procedures which include: an Oral Glucose Tolerance Test (OGTT), additional blood collection, a detailed physical exam, and additional questionnaires.

Discovery Team Review:

The work of the Discovery Team is expected to be an iterative process analyzing all data collected up to this point in the study to understand the significance of novel variants. In some instances, the Discovery Team may determine that enrollment of the Proband's family members is necessary. Family members with suspected atypical diabetes will follow the same study procedures as described above. Affected and unaffected family members may also be enrolled for Sanger Sequencing. The Discovery Team may also recommend additional optional procedures to better characterize the participant's form of diabetes.

Study Design

Study Type:

Observational

Anticipated Enrollment :

2000 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Rare and Atypical Diabetes Network

Actual Study Start Date :

Sep 30, 2020

Anticipated Primary Completion Date :

Sep 1, 2030

Anticipated Study Completion Date :

Sep 1, 2030

Outcome Measures

Primary Outcome Measures

Phenotypic and genotypic characterization of previously unknown forms of diabetes using Whole Genome Sequencing (WGS), and deeper phenotyping methods [Through study completion, an average of 3 years.]
Deeper phenotyping methods include both clinical and laboratory assessments. Clinical data includes anthropometric and biometric data, medical histories, and standard questionnaires (ASA24, PROMIS, environmental exposures depression and anxiety). Laboratory data includes WGS, transcriptomics, metabolomics, mitochondrial sequencing, Oral Glucose Tolerance Test (OGTT), and Islet autoantibodies. Clustering methods will be used to define cohorts of similar diabetes genotypes and phenotypes based on this data.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

The following criteria or phenotypes will be considered for suspecting "atypical" participants:

Type 2 diabetes diagnosed at a time when the individual was prepubertal or non-obese
Mendelian pattern, especially with early onset (<18 years old)
Syndromic (multiple systems involved)
Lipodystrophic
Extremes of BMI
"Mitochondrial" characteristics (e.g., myopathy, hearing deficits)
Non-progressive
Rapidly progressive ("fulminant")
Low insulin requirements (<0.5 u/kg/day)
Cyclical hyperglycemia with periods of remission
Lean persons with polycystic ovarian syndrome (PCOS)
History of gestational diabetes (GDM) when lean
Lean insulin-resistant persons
If islet autoantibodies and beta-cell function parameters have been measured (where "A" = islet cell autoantibodies, "B" = beta-cell function):

oA-B- (i.e., lacking islet autoimmunity makers and lacking beta cell function) oA-B+ with unprovoked DKA at initial presentation (i.e., lacking islet autoimmune markers, with preserved beta-cell function, but presenting with unprovoked DKA) oA-B+ of very young onset (pre-pubertal) (i.e., lacking islet autoimmune markers, with preserved beta-cell function, but very early onset T2D-like phenotype)

Exclusion Criteria:

Those with high likelihood of typical type 1, typical type 2, known monogenic, or other known secondary forms of diabetes
Refusal of consent for genetic testing
Islet autoantibody positive (participants who are islet autoantibody positive but present with additional atypical features i.e. syndromic, strong linear family history of diabetes may not be excluded)
Women who are currently pregnant

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Colorado- Denver	Aurora	Colorado	United States	80045
2	University of Chicago	Chicago	Illinois	United States	60637
3	Indiana University	Indianapolis	Indiana	United States	46202
4	University of Maryland	Baltimore	Maryland	United States	21201
5	Massachusetts General Hospital (MGH)	Boston	Massachusetts	United States	02114
6	University of Michigan	Ann Arbor	Michigan	United States	48109
7	Washington University in St. Louis	Saint Louis	Missouri	United States	63110
8	SUNY Downstate Health Sciences University	Brooklyn	New York	United States	11203
9	Columbia University	New York	New York	United States	10032
10	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27514
11	Vanderbilt University	Nashville	Tennessee	United States	37232
12	Baylor College of Medicine	Houston	Texas	United States	77030
13	Seattle Children's	Seattle	Washington	United States	98105
14	University of Washington	Seattle	Washington	United States	98109