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

• Sponsor: Joslin Diabetes Center (Other)
• Overall Status: Enrolling by invitation
• CT.gov ID: NCT04409795
• Collaborator: (none)
• Enrollment: 21
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 37.2
• Patients Per Site Per Month: 0.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Type 1 Diabetes; Monogenic Diabetes	Drug: Metformin Extended Release Oral Tablet; Drug: Sitagliptin	Phase 2/Phase 3

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 21 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Pilot Trial of Adding Oral Hypoglycemic Therapy to Insulin Treatment in Monogenic Variant Carriers of the Joslin 50-Year Medalist Study
• Actual Study Start Date: Aug 26, 2021
• Anticipated Primary Completion Date: Oct 1, 2024
• Anticipated Study Completion Date: Oct 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Other: 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 (-)	Drug: Metformin Extended Release Oral Tablet; Initial oral hypoglycemic agent added to existing insulin treatment; 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)
Other: 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	Drug: Metformin Extended Release Oral Tablet; Initial oral hypoglycemic agent added to existing insulin treatment; 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)

Outcome Measures

Primary Outcome Measures

1. Glycated hemoglobin (HbA1c) [3 months and 6 months]

   Change in HbA1c (%) between the two study groups

Secondary Outcome Measures

1. Daily insulin dose [3 months and 6 months]

   Change in daily insulin dose (units/kg body weight) between the two study groups

2. Body mass index (BMI) [3 months and 6 months]

   Change in BMI between the two study groups. Weight and height will be combined to report BMI in kg/m^2.

3. C-peptide [3 months and 6 months]

   Change in C-peptide (ng/mL) between the two study groups

4. Total cholesterol [3 months and 6 months]

   Change in total cholesterol (mg/dL) between the two study groups

5. Low density lipoprotein (LDL)-cholesterol [3 months and 6 months]

   Change in LDL-cholesterol (mg/dL) between the two study groups

6. High density lipoprotein (HDL)-cholesterol [3 months and 6 months]

   Change in HDL-cholesterol (mg/dL) between the two study groups

7. Triglycerides [3 months and 6 months]

   Change in triglycerides (mg/dL) between the two study groups

8. Area under the plasma concentration versus time curve (AUC) of C-peptide [6 months]

   Change in AUC of C-peptide between the two study groups, as measured by the hyperglycemic/arginine clamp, at the end of the study

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Joslin Diabetes Center	Boston	Massachusetts	United States	02215

Sponsors and Collaborators

• Joslin Diabetes Center

Investigators

• Principal Investigator: George L. King, MD, Joslin Diabetes Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Joslin Diabetes Center
• ClinicalTrials.gov Identifier: NCT04409795
• Other Study ID Numbers: 2019-76
• First Posted: Jun 1, 2020
• Last Update Posted: Jan 5, 2022
• Last Verified: Jan 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Diabetes Mellitus; Metformin; Sitagliptin Phosphate

Study Results

No Results Posted as of Jan 5, 2022