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Rare and Atypical Diabetes Network (RADIANT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05544266
Recruitment Status : Recruiting
First Posted : September 16, 2022
Last Update Posted : September 16, 2022
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
University of South Florida

Study Description
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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:

  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.

Condition or disease
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
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Study Type : Observational
Estimated Enrollment : 2000 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Rare and Atypical Diabetes Network
Actual Study Start Date : September 30, 2020
Estimated Primary Completion Date : September 2030
Estimated Study Completion Date : September 2030
Groups and Cohorts
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Outcome Measures
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Primary Outcome Measures :
  1. Phenotypic and genotypic characterization of previously unknown forms of diabetes using Whole Genome Sequencing (WGS), and deeper phenotyping methods [ Time Frame: 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.


Biospecimen Retention:   Samples With DNA
Whole Blood Serum Plasma DNA RNA Urine Peripheral Blood Monocytes (PBMCs)

Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Probands and family members will be screened for evaluation of suspected atypical diabetes of unknown origin. Among the pool of evaluated individuals, those found to have a known form of diabetes will be excluded from further study. The remaining participants will be prioritized for genetic/genomic analysis and further testing.
Criteria

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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05544266


Contacts
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Contact: Jeffrey Krischer, PhD 813-396-9501 contact@atypicaldiabetesnetwork.org

Locations
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United States, Colorado
University of Colorado- Denver Recruiting
Aurora, Colorado, United States, 80045
Contact: Courtney King    720-848-6683    courtney.king@ucdenver.edu   
Principal Investigator: Neda Rasouli, MD         
United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Contact: Lisa Letourneau    773-702-0829    lletourneau@uchicago.edu   
Principal Investigator: Lou Philipson, MD, PhD         
Principal Investigator: Siri Greeley, MD, PhD         
United States, Indiana
Indiana University Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Gabriela Monaco    765-701-2941    gamonaco@iu.edu   
Principal Investigator: Carmella Evans-Molina, MD, PhD         
United States, Maryland
University of Maryland Recruiting
Baltimore, Maryland, United States, 21201
Contact: Devon Nwaba    410-706-7764    dnwaba@som.umaryland.edu   
Principal Investigator: Toni Pollin, PhD, MS         
United States, Massachusetts
Massachusetts General Hospital (MGH) Recruiting
Boston, Massachusetts, United States, 02114
Contact: Evelyn Greaux    617-726-1729    EGREAUX@mgh.harvard.edu   
Principal Investigator: Miriam Udler, MD, PhD         
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Adam Neidert    734-615-0539    aneidert@med.umich.edu   
Principal Investigator: Elif Oral, MD         
United States, Missouri
Washington University in St. Louis Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Stacy Hurst    314-747-3294    shurst@wustl.edu   
Principal Investigator: Fumihiko Urano, MD, PhD         
United States, New York
SUNY Downstate Health Sciences University Recruiting
Brooklyn, New York, United States, 11203
Contact: Necole Brown    718-270-4693    necole.brown01@downstate.edu   
Principal Investigator: Mary Ann Banerji, MD         
Columbia University Recruiting
New York, New York, United States, 10032
Contact: James Pring    212-851-5489    jp3735@cumc.columbia.edu   
Principal Investigator: Robin Goland, MD         
United States, North Carolina
University of North Carolina at Chapel Hill Recruiting
Chapel Hill, North Carolina, United States, 27514
Contact: Rachel Fraser    984-974-3011    rachael_fraser@med.unc.edu   
Principal Investigator: John Buse, MD, PhD         
United States, Tennessee
Vanderbilt University Recruiting
Nashville, Tennessee, United States, 37232
Contact: Jordan Smith    615-936-6324    tyler.j.smith@vumc.org   
Principal Investigator: Kevin Niswender, MD, PhD         
United States, Texas
Baylor College of Medicine Recruiting
Houston, Texas, United States, 77030
Contact: Iliana Gonzalez    713-798-5777    iliana.gonzalez@bcm.edu   
Principal Investigator: Ashok Balasubramanyam, MD         
Principal Investigator: Maria Redondo, MD, PhD, MPH         
United States, Washington
Seattle Children's Recruiting
Seattle, Washington, United States, 98105
Contact: Beth Loots    206-884-4488    beth.loots@seattlechildrens.org   
Principal Investigator: Cate Pihoker, MD         
University of Washington Recruiting
Seattle, Washington, United States, 98109
Contact: Dori Khakpour    206-616-1354    dorik@uw.edu   
Principal Investigator: Irl B Hirsch, MD         
Sponsors and Collaborators
University of South Florida
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
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Study Chair: Jeffrey Krischer, PhD University of South Florida
More Information
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Responsible Party: University of South Florida
ClinicalTrials.gov Identifier: NCT05544266    
Other Study ID Numbers: RADIANT
5U54DK118638 ( U.S. NIH Grant/Contract )
5U54DK118612 ( U.S. NIH Grant/Contract )
First Posted: September 16, 2022    Key Record Dates
Last Update Posted: September 16, 2022
Last Verified: August 2022

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of South Florida:
RADIANT
Atypical Diabetes
Rare Diabetes
Glucose Intolerance
Additional relevant MeSH terms:
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Diabetes Mellitus
Metabolic Diseases
Glucose Metabolism Disorders
 Glucose Intolerance
Endocrine System Diseases
Hyperglycemia