search
Back to results

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

Primary Purpose

Type 1 Diabetes, Diabetic Kidney Disease, Cardiovascular Diseases

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Metformin Hcl 1000Mg Tab
Aminohippurate Sodium 20 % Injection
Iohexol 300 Mg/mL Injectable Solution
Placebo
Sponsored by
University of Colorado, Denver
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Type 1 Diabetes focused on measuring Type 1 diabetes, Youth, Insulin sensitivity, Cardiovascular function, Diabetic kidney disease

Eligibility Criteria

12 Years - 21 Years (Child, Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • University of Colorado Anschutz Medical CampusRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Placebo Comparator

Other

Arm Label

Metformin plus automated insulin delivery system

Placebo plus automated insulin delivery system

Multiple daily insulin injections plus continuous glucose monitor

Arm Description

Some participants with type 1 diabetes using an automated insulin delivery system will be randomized to receive treatment with metformin and will undergo RPF (Aminohippurate Sodium Injections 20%), GFR (Iohexol Inj 300 MG/ML), and insulin sensitivity (hyperinsulinemic-euglycemic clamp) assessments, in additional to assessments of cardiovascular and endothelial function.

Some participants with type 1 diabetes using an automated insulin delivery system will be randomized to receive treatment with a placebo pill which is identical in appearance to the metformin pill and will undergo RPF (Aminohippurate Sodium Injections 20%), GFR (Iohexol Inj 300 MG/ML), and insulin sensitivity (hyperinsulinemic-euglycemic clamp) assessments, in additional to assessments of cardiovascular and endothelial function.

Participants with type 1 diabetes using multiple daily injections plus a continuous glucose monitor will not be randomized to receive medication treatment but will undergo RPF (Aminohippurate Sodium Injections 20%), GFR (Iohexol Inj 300 MG/ML), and insulin sensitivity (hyperinsulinemic-euglycemic clamp) assessments, in additional to assessments of cardiovascular and endothelial function.

Outcomes

Primary Outcome Measures

Renal vascular resistance
Renal plasma flow will be measured by para-aminohippurate clearance and used to calculate renal vascular resistance
Glomerular filtration rate
Measured by iohexol clearance

Secondary Outcome Measures

Arterial stiffness
Measured by SphygmoCor
Endothelial function
Measured by EndoPAT
Insulin sensitivity
Measured by hyperinsulinemic-euglycemic clamp

Full Information

First Posted
September 13, 2021
Last Updated
August 21, 2023
Sponsor
University of Colorado, Denver
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
search

1. Study Identification

Unique Protocol Identification Number
NCT05065372
Brief 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
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 1, 2022 (Actual)
Primary Completion Date
January 1, 2026 (Anticipated)
Study Completion Date
July 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Colorado, Denver
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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 12-21 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 1 Diabetes, Diabetic Kidney Disease, Cardiovascular Diseases, Endothelial Dysfunction, Insulin Sensitivity
Keywords
Type 1 diabetes, Youth, Insulin sensitivity, Cardiovascular function, Diabetic kidney disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Metformin plus automated insulin delivery system
Arm Type
Active Comparator
Arm Description
Some participants with type 1 diabetes using an automated insulin delivery system will be randomized to receive treatment with metformin and will undergo RPF (Aminohippurate Sodium Injections 20%), GFR (Iohexol Inj 300 MG/ML), and insulin sensitivity (hyperinsulinemic-euglycemic clamp) assessments, in additional to assessments of cardiovascular and endothelial function.
Arm Title
Placebo plus automated insulin delivery system
Arm Type
Placebo Comparator
Arm Description
Some participants with type 1 diabetes using an automated insulin delivery system will be randomized to receive treatment with a placebo pill which is identical in appearance to the metformin pill and will undergo RPF (Aminohippurate Sodium Injections 20%), GFR (Iohexol Inj 300 MG/ML), and insulin sensitivity (hyperinsulinemic-euglycemic clamp) assessments, in additional to assessments of cardiovascular and endothelial function.
Arm Title
Multiple daily insulin injections plus continuous glucose monitor
Arm Type
Other
Arm Description
Participants with type 1 diabetes using multiple daily injections plus a continuous glucose monitor will not be randomized to receive medication treatment but will undergo RPF (Aminohippurate Sodium Injections 20%), GFR (Iohexol Inj 300 MG/ML), and insulin sensitivity (hyperinsulinemic-euglycemic clamp) assessments, in additional to assessments of cardiovascular and endothelial function.
Intervention Type
Drug
Intervention Name(s)
Metformin Hcl 1000Mg Tab
Other Intervention Name(s)
Fortamet, Glucophage, Glumetza, Riomet
Intervention Description
Agent used to modify insulin sensitivity
Intervention Type
Drug
Intervention Name(s)
Aminohippurate Sodium 20 % Injection
Other Intervention Name(s)
Sodium 4-amino hippurate (PAH) injection 20% (2g/10 mL), Para-aminohippurate, Aminohippuric acid
Intervention Description
Diagnostic aid/agent used to measure renal plasma flow and calculate renal vascular resistance
Intervention Type
Drug
Intervention Name(s)
Iohexol 300 Mg/mL Injectable Solution
Other Intervention Name(s)
Omnipaque 300
Intervention Description
Diagnostic aid/agent used to measure glomerular filtration rate
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Identical to Metformin Hcl 1000Mg Tab but without metabolic effects
Primary Outcome Measure Information:
Title
Renal vascular resistance
Description
Renal plasma flow will be measured by para-aminohippurate clearance and used to calculate renal vascular resistance
Time Frame
4 months
Title
Glomerular filtration rate
Description
Measured by iohexol clearance
Time Frame
4 months
Secondary Outcome Measure Information:
Title
Arterial stiffness
Description
Measured by SphygmoCor
Time Frame
4 months
Title
Endothelial function
Description
Measured by EndoPAT
Time Frame
4 months
Title
Insulin sensitivity
Description
Measured by hyperinsulinemic-euglycemic clamp
Time Frame
4 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lucy Hall, MS
Phone
720-777-2692
Email
Lucy.Hall@childrenscolorado.org
First Name & Middle Initial & Last Name or Official Title & Degree
Kalie Tommerdahl, MD
Phone
720-777-5898
Email
Kalie.Tommerdahl@childrenscolorado.org
Facility Information:
Facility Name
University of Colorado Anschutz Medical Campus
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lucy Hall, MS
Phone
720-777-2692
Email
Lucy.Hall@childrenscolorado.org
First Name & Middle Initial & Last Name & Degree
Kalie Tommerdahl, MD
Phone
720-777-6128
Email
Kalie.Tommerdahl@childrenscolorado.org
First Name & Middle Initial & Last Name & Degree
Kalie Tommerdahl, MD

12. IPD Sharing Statement

Plan to Share IPD
Undecided

Learn more about this trial

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

We'll reach out to this number within 24 hrs