MANATEE-T1D: Metformin ANd AutomaTEd Insulin Delivery System Effects on Renal Vascular Resistance, Insulin Sensitivity, and Cardiometabolic Function in Youth With Type 1 Diabetes

Cardiovascular Diseases Clinical Trial

— MANATEE-T1D  

Official title:

MANATEE-T1D: Metformin ANd AutomaTEd Insulin Delivery System Effects on Renal Vascular Resistance, Insulin Sensitivity, and Cardiometabolic Function in Youth With Type 1 Diabetes

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05065372
• Other study ID #: 21-3483
• Secondary ID: K23HL159292
• Status: Recruiting
• Phase: Phase 1
• Start date: July 1, 2022
• Est. completion date: July 31, 2026

Study information

• Verified date: August 2023
• Source: University of Colorado, Denver
• Contact: Lucy Hall, MS
• Phone: 720-777-2692
• Email: Lucy.Hall[@]childrenscolorado.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Diabetic kidney disease and cardiovascular disease remain the leading causes of morbidity and mortality in people with type 1 diabetes and are exacerbated with longer duration of diabetes and time outside goal glycemic range. Yet, type 1 diabetes is a complex disease with pathophysiology that extends beyond beta-cell injury and insulin deficiency to include insulin resistance and renal vascular resistance, factors that accelerate cardiovascular disease risk. We have shown that metformin improved peripheral insulin sensitivity and vascular stiffness in youth with type 1 diabetes on multiple daily insulin injections or standard insulin pumps. However, metformin's effect on kidney and endothelial outcomes, and the effects of type 1 diabetes technologies, with or without metformin, on any cardiovascular or kidney outcome, remains unknown. Automated insulin delivery systems combine an insulin pump, continuous glucose monitor, and control algorithm to modulate background insulin delivery and decrease peripheral insulin exposure while improving time in target range and reducing hypoglycemia. We hypothesize that automated insulin delivery systems, particularly when combined with metformin, may modulate renal vascular resistance and insulin sensitivity, thereby impacting cardiometabolic function. MANATEE-T1D is a randomized, double-blind, placebo-controlled trial of 4 months of metformin 2,000 mg daily in 40 youth aged 12-21 years with type 1 diabetes on automated insulin delivery systems vs. 20 control youth with type 1 diabetes on multiple daily injections plus a continuous glucose monitor which will assess for changes in calculated renal vascular resistance and gold standard measures of whole-body and adipose insulin sensitivity, arterial stiffness, and endothelial function.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: July 31, 2026
• Est. primary completion date: January 1, 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 12 Years to 21 Years

Eligibility

Inclusion Criteria:

• Youth with pancreatic antibody positive type 1 diabetes
• Age 12-21 years
• Use of an automated insulin delivery system or multiple daily insulin injections plus a continuous glucose monitor for > 6 months
• Pubertal
• Weight > 54 kg and BMI > 5th percentile for age and sex
• Hemoglobin A1c < 11%
• No recent episodes of diabetic ketoacidosis (DKA) or hyperglycemic hyperosmolar syndrome (HHS)

Exclusion Criteria:

• Blood pressure > 140/90 mm Hg
• Anemia
• Estimated glomerular filtration rate < 60 mL/min/1.73 m2 or serum creatinine > 1.2 mg/dL or history of urinary albumin to creatinine ratio = 300mg/g or history of acute kidney injury
• Use of anti-diabetic agents except insulin, angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARB's), diuretics, daily non-steroidal anti-inflammatory drugs (NSAIDs) or aspirin, sulfonamides, procaine, thiazosulfone or probenecid
• Seafood or iodine allergy
• Pregnancy or breast feeding for females

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Diabetic Kidney Disease
• Diabetic Nephropathies
• Endothelial Dysfunction
• Hypersensitivity
• Insulin Resistance
• Insulin Sensitivity
• Kidney Diseases
• Type 1 Diabetes

Intervention

Drug:
• Metformin Hcl 1000Mg Tab
Agent used to modify insulin sensitivity
• Aminohippurate Sodium 20 % Injection
Diagnostic aid/agent used to measure renal plasma flow and calculate renal vascular resistance
• Iohexol 300 Mg/mL Injectable Solution
Diagnostic aid/agent used to measure glomerular filtration rate
• Placebo
Identical to Metformin Hcl 1000Mg Tab but without metabolic effects

Locations

Country	Name	City	State
United States	University of Colorado Anschutz Medical Campus	Aurora	Colorado

Sponsors (2)

Lead Sponsor	Collaborator
University of Colorado, Denver	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Renal vascular resistance	Renal plasma flow will be measured by para-aminohippurate clearance and used to calculate renal vascular resistance	4 months
Primary	Glomerular filtration rate	Measured by iohexol clearance	4 months
Secondary	Arterial stiffness	Measured by SphygmoCor	4 months
Secondary	Endothelial function	Measured by EndoPAT	4 months
Secondary	Insulin sensitivity	Measured by hyperinsulinemic-euglycemic clamp	4 months