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NCT Number: NCT06609356

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

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.

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Key information

Conditions

Type 1 Diabetes Mellitus Autoimmune Diseases Diabetes Mellitus Diabetes Mellitus, Type 1 Endocrine System Diseases Glucokinase-Maturity Onset Diabetes of the Young (GCK-MODY) Glucose Metabolism Disorders Healthy Volunteer Hyperinsulinism Immune System Diseases Insulin Resistance MODY2 Diabetes Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year–60 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Early Phase 1

Primary location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location status: Recruiting

Location contact

Daniel J Moore, MD, PhD

CONTACT

[email protected]

(615) 322- 7427

Danield J Moore, MD, PhD

PRINCIPAL_INVESTIGATOR

Wendi Welch, CCRP

CONTACT

[email protected]

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Study Visit 1

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

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

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

Drug

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

Primary outcomes

  1. Aim 1: Tissue glucose disposal (TGD)

    Time frame: 8 hours

    The primary outcome will be the difference in tissue glucose disposal (TGD) during a hyperinsulinemic, euglycemic clamp between Eu-Ins and Hi-Ins studies.

  2. Aim 2: Nitric Oxide (NO) bioavailability

    Time frame: 8 hours

    This study aims to determine the difference in hyperinsulinemia-mediated suppression of nitric oxide (NO) bioavailability between Eu-Ins and Hi-Ins studies, as measured by flow mediated dilation (FMD) of the brachial artery.

Secondary outcomes

  1. Secondary outcome for Aim 1: Differences in endogenous glucose production

    Time frame: 8 hours

    This study aims to determine the difference in endogenous glucose production at the end of euinsulinemic vs. hyperinsulinemic infusions

  2. Secondary outcome for Aim 2: Nitroglycerin mediated vasodilation of the brachial artery

    Time frame: 8 hours

    Through the use of flow mediated dilation (FMD), the study aims to determine nitroglycerin mediated vasodilation of the brachial artery.

Study contacts

Contact information is provided by the study sponsor or research team.

Daniel J Moore, MD, PhD

CONTACT

[email protected]

615-322-7427

Sponsors and collaborators

Lead sponsor

Vanderbilt University Medical Center

Other

Registry information

Acronym: ACT T1D

Important dates

Study start
2025
Primary completion
2027
Study completion
2027
First posted
Sep 24, 2024
Registry last updated
Dec 23, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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