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

NCT04409795 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: 2019-76
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Glycated hemoglobin (HbA1c)

  Change in HbA1c (%) between the two study groups

  3 months and 6 months

Secondary Outcomes (8)

• Daily insulin dose

  3 months and 6 months

• Body mass index (BMI)

  3 months and 6 months

• C-peptide

  3 months and 6 months

• Total cholesterol

  3 months and 6 months

• Low density lipoprotein (LDL)-cholesterol

  3 months and 6 months

Study Arms (2)

HLA+ Group

OTHER

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 (-)

Drug: Metformin Extended Release Oral Tablet; Drug: Sitagliptin

HLA- Group

OTHER

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

Drug: Metformin Extended Release Oral Tablet; Drug: Sitagliptin

Interventions

Metformin Extended Release Oral Tablet DRUG

Initial oral hypoglycemic agent added to existing insulin treatment

HLA+ Group; HLA- Group

Sitagliptin 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; HLA- Group

Eligibility Criteria

• Age: Up to 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Joslin Diabetes Center: lead

Study Sites (1)

Joslin Diabetes Center

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Sitagliptin Phosphate

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines

Study Officials

• George L. King, MD

  Joslin Diabetes Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2019
• First Posted: June 1, 2020
• Study Start: August 26, 2021
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: February 24, 2025

Record last verified: 2025-02

Locations

US (1)