Clinical trial NCT05065372: MANATEE-T1D: Metformin ANd AutomaTEd Insulin Delivery System Effects on Renal Vascular Resistance, Insulin Sensitivity, and Cardiometabolic Function in Youth With Type 1 Diabetes
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Type 1 Diabetes
Diabetic Kidney Disease
Cardiovascular Diseases
Endothelial Dysfunction
Insulin Sensitivity
Keywords: Type 1 diabetes
Youth
Insulin sensitivity
Cardiovascular function
Diabetic kidney disease
Lead sponsor: Seattle Children's Hospital
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: University of Colorado, Denver
First posted: 2021-10-04
Enrollment: 60
Sex: ALL
Minimum age (years): 12
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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 12-25 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 or an insulin pump in manual mode 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.


Eligibility criteria: Inclusion Criteria:

* T1D and using an automated insulin delivery system or multiple daily insulin injections/manual insulin pump plus continuous glucose monitor for \> 6 months
* Age 12-25 years
* Use of an automated insulin delivery system or multiple daily insulin injections plus a continuous glucose monitor or an insulin pump in manual mode plus a continuous glucose monitor for \> 6 months
* Hemoglobin A1c \< 11%
* No recent episodes of diabetic ketoacidosis (DKA) or hyperglycemic hyperosmolar syndrome (HHS) (within 30 days)
* Pubertal (Tanner stage ≥ 2)
* Weight \> 54 kg and BMI \> 5th percentile for age and sex

Exclusion Criteria:

* Blood pressure \> 140/90 mm Hg
* Hemoglobin \< 9 g/dL
* 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

Primary outcomes:
measure: Renal vascular resistance
timeFrame: 4 months
measure: Glomerular filtration rate
timeFrame: 4 months
Secondary outcomes:
measure: Arterial stiffness
timeFrame: 4 months
measure: Insulin sensitivity
timeFrame: 4 months
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Children's Hospital Colorado/University of Colorado Anschutz Medical Campus
state: Colorado
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
Study officials:
References: