NCT06609356 · Vanderbilt University Medical Center
Cardiometabolic Benefit of Reducing Iatrogenic Hyperinsulinemia Using Insulin Adjunctive Therapy in Type 1 Diabetes
(ACT T1D)
What this study is about
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.
View original scientific description
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.
Interventions
PROCEDURE
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)
DRUG
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.
PROCEDURE
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.
DRUG
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 measures
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.
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.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
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
- Any thiazide diuretic
- Any oral contraceptive pill with greater than 35 mcg ethinyl estradiol
- Growth hormone
- Any immunosuppressant
- Antihypertensive
- Any antihyperlipidemic Other:
- 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
Where
- Nashville, Tennessee
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Dec 23, 2025 · Source of record for eligibility and locations