Recruiting
Early Phase 1

SGLT2 Inhibitor

Sponsor:

Vanderbilt University Medical Center

Code:

NCT06609356

Conditions

Type 1 Diabetes Mellitus

Glucokinase-Maturity Onset Diabetes of the Young (GCK-MODY)

MODY2 Diabetes

Healthy Volunteer

Eligibility Criteria

Sex: All

Age: 18 - 60

Healthy Volunteers: Accepted

Interventions

Study Visit 1

Placebo

Study Visit 2

Sodium Glucose Co-transporter 2 (SGLT2) Inhibitor

Study Details

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 ID

NCT06609356

Start date

Jul 3, 2025

Status verified date

Dec, 2025

Completion date

Dec, 2027

Anticipated

Primary completion date

Jul, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 60

Healthy Volunteers: Accepted

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: Severe Hypoglycemia: ≥1 episode in the past 3 months

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

Study Design

Enrollment

27 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: 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.

active comparator: 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.

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)

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.

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.

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).

Primary outcome measure

  • Aim 1: Tissue glucose disposal (TGD) [ Time Frame: 8 hours ]
  • Aim 2: Nitric Oxide (NO) bioavailability [ Time Frame: 8 hours ]

Central Contacts and Locations

Central contacts

Daniel J Moore, MD, PhD

615-322-7427metabolism@vumc.org

Locations

Vanderbilt University Medical Center

Recruiting

Nashville, Tennessee, United States, 37232

Contacts

Daniel J Moore, MD, PhD

(615) 322- 7427metabolism@vumc.org

Wendi Welch, CCRP

wendi.m.welch@vumc.org

Principal Investigator:

Danield J Moore, MD, PhD

More Information

Sponsor

Vanderbilt University Medical Center

Last update posted

Dec 23, 2025

Last verified

Dec, 2025

Keywords

  • type 1 diabetes mellitus
  • with Glucokinase-Maturity Onset Diabetes of the Young (GCK-MODY)
  • nitric oxide
  • sodium-glucose cotransporter-2 inhibitors (SGLT2i)
  • healthy volunteer
  • insulin sensitivity
  • flow-mediated vasodilation (FMD)

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Vanderbilt University Medical Center on 2025-12-23.