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

Type 1 Diabetes Clinical Trial

Official title:

A Pilot Trial of Adding Oral Hypoglycemic Therapy to Insulin Treatment in Monogenic Variant Carriers of the Joslin 50-Year Medalist Study

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04409795
• Other study ID #: 2019-76
• Status: Enrolling by invitation
• Phase: Phase 2/Phase 3
• Start date: August 26, 2021
• Est. completion date: December 2024

Study information

• Verified date: March 2024
• Source: Joslin Diabetes Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 21
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Monogenic Diabetes
• Type 1 Diabetes

Intervention

Drug:
• Metformin Extended Release Oral Tablet
Initial oral hypoglycemic agent added to existing insulin treatment
• Sitagliptin
Secondary oral hypoglycemic agent added to existing insulin treatment (for those who are intolerant to or unable to achieve glycemic targets with metformin)

Locations

Country	Name	City	State
United States	Joslin Diabetes Center	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Joslin Diabetes Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Glycated hemoglobin (HbA1c)	Change in HbA1c (%) between the two study groups	3 months and 6 months
Secondary	Daily insulin dose	Change in daily insulin dose (units/kg body weight) between the two study groups	3 months and 6 months
Secondary	Body mass index (BMI)	Change in BMI between the two study groups. Weight and height will be combined to report BMI in kg/m^2.	3 months and 6 months
Secondary	C-peptide	Change in C-peptide (ng/mL) between the two study groups	3 months and 6 months
Secondary	Total cholesterol	Change in total cholesterol (mg/dL) between the two study groups	3 months and 6 months
Secondary	Low density lipoprotein (LDL)-cholesterol	Change in LDL-cholesterol (mg/dL) between the two study groups	3 months and 6 months
Secondary	High density lipoprotein (HDL)-cholesterol	Change in HDL-cholesterol (mg/dL) between the two study groups	3 months and 6 months
Secondary	Triglycerides	Change in triglycerides (mg/dL) between the two study groups	3 months and 6 months
Secondary	Area under the plasma concentration versus time curve (AUC) of C-peptide	Change in AUC of C-peptide between the two study groups, as measured by the hyperglycemic/arginine clamp, at the end of the study	6 months