Back to results

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

Primary Purpose

Type 1 Diabetes, Monogenic Diabetes

Status

Enrolling by invitation

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Metformin Extended Release Oral Tablet

Sitagliptin

About this trial

This is an interventional treatment trial for Type 1 Diabetes

Eligibility Criteria

undefined - 85 Years (Child, Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

Joslin Diabetes Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Arm Label

HLA+ Group

HLA- Group

Arm 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 (-)

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

Outcomes

Primary Outcome Measures

Glycated hemoglobin (HbA1c)

Change in HbA1c (%) between the two study groups

Secondary Outcome Measures

Daily insulin dose

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

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.

C-peptide

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

Total cholesterol

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

Low density lipoprotein (LDL)-cholesterol

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

High density lipoprotein (HDL)-cholesterol

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

Triglycerides

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

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

Full Information

NCT ID

NCT04409795

First Posted

November 14, 2019

Last Updated

February 22, 2023

Sponsor

Joslin Diabetes Center

1. Study Identification

Unique Protocol Identification Number

NCT04409795

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

February 2023

Overall Recruitment Status

Enrolling by invitation

Study Start Date

August 26, 2021 (Actual)

Primary Completion Date

October 2024 (Anticipated)

Study Completion Date

October 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Joslin Diabetes Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Type 1 Diabetes, Monogenic Diabetes

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

21 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

HLA+ Group

Arm Type

Other

Arm Description

Arm Title

HLA- Group

Arm Type

Other

Arm Description

Intervention Type

Drug

Intervention Name(s)

Metformin Extended Release Oral Tablet

Intervention Description

Initial oral hypoglycemic agent added to existing insulin treatment

Intervention Type

Drug

Intervention Name(s)

Sitagliptin

Intervention Description

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

Primary Outcome Measure Information:

Title

Glycated hemoglobin (HbA1c)

Description

Change in HbA1c (%) between the two study groups

Time Frame

3 months and 6 months

Secondary Outcome Measure Information:

Title

Daily insulin dose

Description

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

Time Frame

3 months and 6 months

Title

Body mass index (BMI)

Description

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

Time Frame

3 months and 6 months

Title

C-peptide

Description

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

Time Frame

3 months and 6 months

Title

Total cholesterol

Description

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

Time Frame

3 months and 6 months

Title

Low density lipoprotein (LDL)-cholesterol

Description

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

Time Frame

3 months and 6 months

Title

High density lipoprotein (HDL)-cholesterol

Description

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

Time Frame

3 months and 6 months

Title

Triglycerides

Description

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

Time Frame

3 months and 6 months

Title

Area under the plasma concentration versus time curve (AUC) of C-peptide

Description

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

Time Frame

6 months

10. Eligibility

Sex

All

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

George L. King, MD

Organizational Affiliation

Joslin Diabetes Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Joslin Diabetes Center

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02215

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs