Cardiometabolic Benefit of Reducing Iatrogenic Hyperinsulinemia Using Insulin Adjunctive Therapy in Type 1 Diabetes

NCT ID: NCT06609356

Last Updated: 2025-12-23

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-07-03
• Study Completion Date: 2027-12-31

Brief Summary

This study aims to understand the heart and blood sugar health benefits of using an adjunctive therapy to lower high insulin levels in people with type 1 diabetes. The investigators will also look at people with a specific type of diabetes called Glucokinase-Maturity Onset Diabetes of the Young (GCK-MODY) and those without diabetes to help interpret the results. The investigators will use a medication that helps the body get rid of sugar, called and SGLT2 inhibitor, with the goal to reduce the body's insulin requirements. The investigators believe this could lead to better heart and blood sugar health, including a better response to insulin and more available nitric oxide, a gas that helps blood vessels function well. The investigators will compare heart and blood sugar health risk factors in participants with type 1 diabetes, participants with Glucokinase-Maturity Onset Diabetes of the Young (GCK-MODY), and non-diabetic healthy volunteers under two conditions: high insulin levels typical of type 1 diabetes and normal insulin levels typical of the other two groups.

Conditions

Type 1 Diabetes Mellitus; Glucokinase-Maturity Onset Diabetes of the Young (GCK-MODY); MODY2 Diabetes; Healthy Volunteer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

High insulin

Participants will receive a "high insulin infusion" (Hi-Ins) prior to quantifying insulin resistance and endothelial function. This infusion will result in participants having insulin levels similar to patients with type 1 diabetes for five hours.

Group Type: EXPERIMENTAL

Study Visit 1

Intervention Type: PROCEDURE

Hyperinsulinemic, euglycemic clamp and flow-mediated dilation (FMD) study. The study will randomize participants to first receive a five-hour intravenous insulin infusion to achieve normal plasma insulin concentrations (Eu-Ins) or higher plasma insulin concentrations (Hi-Ins)

Placebo

Intervention Type: DRUG

• T1DM participants in the Hi-Ins study will receive an oral placebo. During the Eu-Ins study they will receive an SGLT2i.
• CGK-MODY participants and healthy volunteers will receive placebo in both studies.

Study Visit 2

Intervention Type: PROCEDURE

Hyperinsulinemic, euglycemic clamp and flow-mediated dilation (FMD) study. Insulin levels infused during the five-hour insulin infusion will be opposite of the first visit.

Normal insulin

Participants will receive a "normal insulin infusion" (Eu-Ins) prior to quantifying insulin resistance and endothelial function. This infusion will result in participants having insulin levels similar to people without diabetes and people with GCK-MODY for five hours.

Group Type: ACTIVE_COMPARATOR

Study Visit 1

Intervention Type: PROCEDURE

Hyperinsulinemic, euglycemic clamp and flow-mediated dilation (FMD) study. The study will randomize participants to first receive a five-hour intravenous insulin infusion to achieve normal plasma insulin concentrations (Eu-Ins) or higher plasma insulin concentrations (Hi-Ins)

Placebo

Intervention Type: DRUG

• T1DM participants in the Hi-Ins study will receive an oral placebo. During the Eu-Ins study they will receive an SGLT2i.
• CGK-MODY participants and healthy volunteers will receive placebo in both studies.

Study Visit 2

Intervention Type: PROCEDURE

Hyperinsulinemic, euglycemic clamp and flow-mediated dilation (FMD) study. Insulin levels infused during the five-hour insulin infusion will be opposite of the first visit.

Sodium Glucose Co-transporter 2 (SGLT2) Inhibitor

Intervention Type: DRUG

Concurrent with starting the five-hour infusion, T1DM participants in the Eu-Ins study will receive an SGLT2i dose (empagliflozin 25 mg).

Interventions

Study Visit 1

Hyperinsulinemic, euglycemic clamp and flow-mediated dilation (FMD) study. The study will randomize participants to first receive a five-hour intravenous insulin infusion to achieve normal plasma insulin concentrations (Eu-Ins) or higher plasma insulin concentrations (Hi-Ins)

Intervention Type: PROCEDURE

Placebo

• T1DM participants in the Hi-Ins study will receive an oral placebo. During the Eu-Ins study they will receive an SGLT2i.
• CGK-MODY participants and healthy volunteers will receive placebo in both studies.

Intervention Type: DRUG

Study Visit 2

Hyperinsulinemic, euglycemic clamp and flow-mediated dilation (FMD) study. Insulin levels infused during the five-hour insulin infusion will be opposite of the first visit.

Intervention Type: PROCEDURE

Sodium Glucose Co-transporter 2 (SGLT2) Inhibitor

Concurrent with starting the five-hour infusion, T1DM participants in the Eu-Ins study will receive an SGLT2i dose (empagliflozin 25 mg).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Age: 18-60 years BMI: 18-28 kg/m² Weight: ≥ 50 kg

T1DM Participants:

Duration of T1DM: 1-30 years HbA1c: 5.7-7.5% Insulin Therapy: Using automated insulin delivery

GCK-MODY Participants:

HbA1c: 5.7-7.5% Genetic Confirmation: Positive GCK sequencing

Control Participants:

HbA1c: less than 5.5%

Exclusion Criteria

Comorbidities:

• Any hospital admissions for diabetic ketoacidosis in the past 6 months
• SBP greater than 140 mmHg and DBP greater than 100 mmHg
• eGFR by MDRD equation of less than 60 mL/min/1.73 m²
• AST or ALT greater than 2.5 times ULN
• Hct less than 35%

Medications:

• Any antioxidant vitamin supplement within 2 weeks before the study
• Any systemic glucocorticoid
• Antipsychotics
• Atenolol, Metoprolol, Propranolol
• Niacin
• Any thiazide diuretic
• Any oral contraceptive pill with greater than 35 mcg ethinyl estradiol
• Growth hormone
• Any immunosuppressant
• Antihypertensive
• Any antihyperlipidemic

Other:

• Pregnancy
• Tanner stage less than 5
• Peri- or post-menopausal women
• Active smoker

T1DM Participants:

Medications: Any diabetes medication except insulin C-peptide: greater than 0.7 ng/mL (fasting)

GCK-MODY Participants:

None specific

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Vanderbilt University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Daniel Moore

Associate Professor of Pediatrics, Division of Pediatric Endocrinology and Diabetes

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Daniel J Moore, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University Medical Center

Locations

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Daniel J Moore, MD, PhD

Role: CONTACT

metabolism@vumc.org

615-322-7427

Facility Contacts

Daniel J Moore, MD, PhD

Role: primary

metabolism@vumc.org

(615) 322- 7427

Wendi Welch, CCRP

Role: backup

wendi.m.welch@vumc.org

Other Identifiers

240996

Identifier Type: -

Identifier Source: org_study_id