Type 1 Diabetes MellitusEarly Phase 1ACT T1DNCT06609356
Cardiometabolic Benefit of Reducing Iatrogenic Hyperinsulinemia Using Insulin Adjunctive Therapy in Type 1 Diabetes
A Early Phase 1 study testing Study Visit 1, Study Visit 2 and Sodium Glucose Co-transporter 2 (SGLT2) Inhibitor in people with Type 1 Diabetes Mellitus and Glucokinase-Maturity Onset Diabetes of the Young (GCK-MODY), run by Vanderbilt University Medical Center at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Type 1 Diabetes Mellitus, Glucokinase-Maturity Onset Diabetes of the Young (GCK-MODY), MODY2 Diabetes
- What is being tested?
- Study Visit 1, Study Visit 2 and Sodium Glucose Co-transporter 2 (SGLT2) Inhibitor
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 27 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Jul 2025to Dec 2027
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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:
Show all 35Show fewer
- 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
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Daniel J Moore, MD, PhD, (615) 322- 7427, metabolism@vumc.org
Wendi Welch, CCRP, wendi.m.welch@vumc.org
About this study
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
- Being tested
- Study Visit 1, Placebo, Study Visit 2, Sodium Glucose Co-transporter 2 (SGLT2) Inhibitor
- 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)
- Medical subject headings
- Diabetes Mellitus, Type 1, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Study Visit 1Procedure or surgery
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)
PlaceboDrug
- 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 2Procedure or surgery
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) InhibitorDrug
Concurrent with starting the five-hour infusion, T1DM participants in the Eu-Ins study will receive an SGLT2i dose (empagliflozin 25 mg).
| Study group | Role | What they receive |
|---|---|---|
| High insulin | Experimental | 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. Receives: Procedure: Study Visit 1; Drug: Placebo; Procedure: Study Visit 2 |
| Normal insulin | Active comparator | 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. Receives: Procedure: Study Visit 1; Drug: Placebo; Procedure: Study Visit 2; Drug: Sodium Glucose Co-transporter 2 (SGLT2) Inhibitor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Aim 1: Tissue glucose disposal (TGD)
The primary outcome will be the difference in tissue glucose disposal (TGD) during a hyperinsulinemic, euglycemic clamp between Eu-Ins and Hi-Ins studies.
Measured: 8 hours
Aim 2: Nitric Oxide (NO) bioavailability
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.
Measured: 8 hours
Secondary outcomes (2)
Secondary outcome for Aim 1: Differences in endogenous glucose production
This study aims to determine the difference in endogenous glucose production at the end of euinsulinemic vs. hyperinsulinemic infusions
Measured: 8 hours
Secondary outcome for Aim 2: Nitroglycerin mediated vasodilation of the brachial artery
Through the use of flow mediated dilation (FMD), the study aims to determine nitroglycerin mediated vasodilation of the brachial artery.
Measured: 8 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2024
- Study start3 Jul 2025
- Primary completionJul 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 1 Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by Vanderbilt University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 27 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Daniel Moore, Vanderbilt University Medical Center
- Investigators
- Daniel J Moore, MD, PhD, Principal investigator, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06609356
- Sponsor's protocol ID
- 240996
- Acronym
- ACT T1D
- Status last verified
- Dec 2025
- First submitted
- 20 Sep 2024
- Last updated
- 23 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie the results reported in a published article after deidentification (text, tables, figures, and appendices).
Study at a glance
From the registry record, last updated by the sponsor on 23 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cardiometabolic Benefit of Reducing Iatrogenic Hyperinsulinemia Using Insulin Adjunctive Therapy in Type 1 Diabetes
- ClinicalTrials.gov ID
- NCT06609356
- Acronym / sponsor ID
- ACT T1D / 240996
- Conditions
- Type 1 Diabetes Mellitus, Glucokinase-Maturity Onset Diabetes of the Young (GCK-MODY), MODY2 Diabetes, Healthy Volunteer
- 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)
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 27 participants (estimated)
- Lead sponsor
- Vanderbilt University Medical CenterUniversity, hospital or other
- Study start
- 3 Jul 2025 (actual)
- Primary completion
- Jul 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 24 Sep 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| High insulin | Experimental | Procedure: Study Visit 1, Drug: Placebo, Procedure: Study Visit 2Participants 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. |
| Normal insulin | Active comparator | Procedure: Study Visit 1, Drug: Placebo, Procedure: Study Visit 2, Drug: Sodium Glucose Co-transporter 2 (SGLT2) InhibitorParticipants 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. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (35 listed)
- Age: 18-60 years BMI: 18-28 kg/m² Weight: ≥ 50 kg
- Duration of T1DM: 1-30 years HbA1c: 5.7-7.5% Insulin Therapy: Using automated insulin delivery
- HbA1c: 5.7-7.5% Genetic Confirmation: Positive GCK sequencing
- HbA1c: less than 5.5%
- Exclusion Criteria: Severe Hypoglycemia: ≥1 episode in the past 3 months
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Study Visit 1Hyperinsulinemic, 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) | Procedure or surgery | High insulin, Normal insulin |
| 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. | Drug | High insulin, Normal insulin |
| Study Visit 2Hyperinsulinemic, euglycemic clamp and flow-mediated dilation (FMD) study. Insulin levels infused during the five-hour insulin infusion will be opposite of the first visit. | Procedure or surgery | High insulin, Normal insulin |
| Sodium Glucose Co-transporter 2 (SGLT2) InhibitorConcurrent with starting the five-hour infusion, T1DM participants in the Eu-Ins study will receive an SGLT2i dose (empagliflozin 25 mg). | Drug | Normal insulin |
Primary outcome
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.
2 secondary outcomes
Secondary outcome for Aim 1: Differences in endogenous glucose production
Time frame: 8 hours
Secondary outcome for Aim 2: Nitroglycerin mediated vasodilation of the brachial artery
Time frame: 8 hours
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Dec 2025.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie the results reported in a published article after deidentification (text, tables, figures, and appendices).
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Daniel J Moore, MD, PhD principal investigator
Vanderbilt University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Study Visit 1, Study Visit 2 and Sodium Glucose Co-transporter 2 (SGLT2) Inhibitor in people with Type 1 Diabetes Mellitus and Glucokinase-Maturity Onset Diabetes of the Young (GCK-MODY), run by Vanderbilt University Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 35 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 23 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Daniel J Moore, MD, PhD (615-322-7427, metabolism@vumc.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Aim 1: Tissue glucose disposal (TGD) (time frame: 8 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Dec 2025.