Rare and Atypical Diabetes Network

Diabetes Mellitus Clinical Trial

— RADIANT  

Official title:

Rare and Atypical Diabetes Network

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05544266
• Other study ID #: RADIANT
• Secondary ID: 5U54DK1186385U54
• Status: Recruiting
• Start date: September 30, 2020
• Est. completion date: September 2030

Study information

• Verified date: August 2022
• Source: University of South Florida
• Contact: Jeffrey Krischer, PhD
• Phone: 813-396-9501
• Email: contact[@]atypicaldiabetesnetwork.org
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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:

1. Identify and enroll individuals and families with undiagnosed rare and atypical forms of diabetes.

2. Determine the etiologic basis of the metabolic disorder among individuals and families with novel forms of rare and atypical diabetes.

3. Understand the pathophysiology of individuals and families with novel forms of rare and atypical forms of diabetes.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2000
• Est. completion date: September 2030
• Est. primary completion date: September 2030
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus Progression
• Endocrine System Diseases
• Endocrine; Complications
• Glucose Intolerance
• Glucose Metabolism Disorders
• Metabolic Disease
• Metabolic Diseases

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	University of Colorado- Denver	Aurora	Colorado
United States	University of Maryland	Baltimore	Maryland
United States	Massachusetts General Hospital (MGH)	Boston	Massachusetts
United States	SUNY Downstate Health Sciences University	Brooklyn	New York
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	University of Chicago	Chicago	Illinois
United States	Baylor College of Medicine	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	Vanderbilt University	Nashville	Tennessee
United States	Columbia University	New York	New York
United States	Washington University in St. Louis	Saint Louis	Missouri
United States	Seattle Children's	Seattle	Washington
United States	University of Washington	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
University of South Florida	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phenotypic and genotypic characterization of previously unknown forms of diabetes using Whole Genome Sequencing (WGS), and deeper phenotyping methods	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.	Through study completion, an average of 3 years.