Oral Hypoglycemic Therapy for Monogenic Variant Carriers of the Joslin Medalist Study

Joslin Diabetes Center

Status and phase: Completed; Phase 3; Phase 2

Conditions: Type 1 Diabetes; Monogenic Diabetes

Treatments: Drug: Metformin Extended Release Oral Tablet; Drug: Sitagliptin

Study type: Interventional

Funder types: Other

Identifiers

NCT04409795

2019-76

Details and patient eligibility

About

The purpose of this study is to evaluate the efficacy of adding oral hypoglycemic agents (OHA) to existing insulin treatment in monogenic variant carriers of the Joslin 50-Year Medalist Study ("Medalists"), who are characterized by ≥50 years of insulin-dependent diabetes. Our primary objective is to evaluate whether the presence of human leukocyte antigen (HLA) high-risk alleles for diabetes (DR3 and/or DR4) can affect the effectiveness of OHA in these subjects.

Enrollment: 3 patients

Sex: All

Ages: Under 85 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Existing participants in the Joslin 50-Year Medalist Study
• Residing in the United States
• Capable of giving informed consent
• Known detectable C-peptide >0.05 ng/mL

Exclusion criteria

• Known diagnosis of cancer or active inflammatory disease such as rheumatoid arthritis, lupus, and inflammatory bowel disease
• Recent history of myocardial infarction, angioplasty, bypass surgery, heart failure, angina, stroke, or uncontrolled hypertension>160/100 during the past 3 months
• Known diagnosis of cognitive dysfunction, dementia or Alzheimer's disease
• Pre-existing liver disease or liver function tests (AST or ALT)>3x the upper limit of normal
• Pre-existing kidney disease (Chronic Kidney Disease Stage IV and below, or estimated glomerular filtration rate<45 mL/min/1.73 m2)
• Active use of immunosuppressants
• Recipients of prior islet cell or pancreas transplantation
• Inability to travel due to frailty or health reasons
• Donated blood within the previous two (2) months

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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3 participants in 2 patient groups

HLA+ Group

Other group

Description:

Participants who are high-risk HLA-DR3 and/or DR4 (+); monogenic variant (+) with rare exome variant ensemble learner (REVEL) score\>0.75; and both glutamic acid decarboxylase (GAD65) and islet antigen (IA2) autoantibody (-)

Treatment:

Drug: Sitagliptin

Drug: Metformin Extended Release Oral Tablet

HLA- Group

Other group

Description:

Participants who are high-risk HLA-DR3 and DR4 (-); with known or yet unknown monogenic variants with REVEL score\>0.75; and either GAD65 and IA2 autoantibody (-), or autoantibody (+) with titers close to the cutoff

Treatment:

Drug: Sitagliptin

Drug: Metformin Extended Release Oral Tablet