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

NCT ID: NCT04409795

Last Updated: 2025-02-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-08-26
• Study Completion Date: 2024-12-31

Brief Summary

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.

Conditions

Type 1 Diabetes; Monogenic Diabetes

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

HLA+ Group

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 (-)

Group Type: OTHER

Metformin Extended Release Oral Tablet

Intervention Type: DRUG

Initial oral hypoglycemic agent added to existing insulin treatment

Sitagliptin

Intervention Type: DRUG

Secondary oral hypoglycemic agent added to existing insulin treatment (for those who are intolerant to or unable to achieve glycemic targets with metformin)

HLA- Group

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

Group Type: OTHER

Metformin Extended Release Oral Tablet

Intervention Type: DRUG

Initial oral hypoglycemic agent added to existing insulin treatment

Sitagliptin

Intervention Type: DRUG

Secondary oral hypoglycemic agent added to existing insulin treatment (for those who are intolerant to or unable to achieve glycemic targets with metformin)

Interventions

Metformin Extended Release Oral Tablet

Initial oral hypoglycemic agent added to existing insulin treatment

Intervention Type: DRUG

Sitagliptin

Secondary oral hypoglycemic agent added to existing insulin treatment (for those who are intolerant to or unable to achieve glycemic targets with metformin)

Intervention Type: DRUG

Eligibility Criteria

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

• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Joslin Diabetes Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

George L. King, MD

Role: PRINCIPAL_INVESTIGATOR

Joslin Diabetes Center

Locations

Joslin Diabetes Center

Boston, Massachusetts, United States

Countries

United States

Other Identifiers

2019-76

Identifier Type: -

Identifier Source: org_study_id