Adolescent Type 1 Diabetes Treatment With SGLT2i for hyperglycEMia & hyPerfilTration Trial

Study Overview
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Brief Summary
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The ATTEMPT (Adolescent Type 1 diabetes Treatment with SGLT2i for hyperglycEMia & hyPerfilTration Trial) is a multi-center, double-blinded, randomized, placebo-controlled trial to evaluate the effect of treatment with Dapagliflozin when compared to placebo, in combination with adjustable insulin, on measured GFR in adolescents with T1D 12 to <19 years of age over a 16-week treatment period.

Detailed Description
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The ATTEMPT (Adolescent Type 1 diabetes Treatment with SGLT2i for hyperglycEMia & hyPerfilTration Trial) is designed to evaluate the impact of Dapagliflozin versus placebo in combination with insulin therapy. This trial will assess detailed renal mechanistic evaluations, with direct measurement of GFR, to understand the important physiologic impacts of SGLT2 inhibition on the early onset manifestations and progression of diabetes complications within this age group. Fundamentally, the ATTEMPT trial will provide essential information in establishing a framework for this young cohort to evaluate key physiologic, mechanistic and metabolic outcomes.

Official Title
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Adolescent Type 1 Diabetes Treatment With SGLT2i for hyperglycEMia & hyPerfilTration Trial

Conditions
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Diabetes Mellitus, Type 1

Intervention / Treatment
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* Drug: Dapagliflozin 5mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Capacity to consent; participants or their parents/legal guardians or responsible representatives must be willing and able to give signed informed consent. Participants without capacity must provide assent where applicable. Diagnosis of Type 1 Diabetes, defined by American Diabetes Association Criteria, for at least 12 months. Sex: Male and Female. Age: 12 years to <19 years. HbA1c: 7.0-10 % at time of screening. Participants with a lower (6.5 to <7.0%) or a higher HbA1c (>10.0 to 11.0%) may be considered, based upon investigator discretion, if patient is adherent with study safety criteria, including a good understanding of diabetes management, regular and consistent blood glucose monitoring, appropriate ketone testing and DKA symptom recognition, appropriate adjustment of insulin doses for meals and activity as well as illness. On Insulin Therapy: Daily injections, to include TID (three times a day), multiple daily dose insulin injection (MDI, > 3 injections daily) or Pump (CSII). A minimum total daily dose (TDD) of insulin ≥0.6 Units/kilogram/day. Females of child bearing potential must be willing to use medically acceptable contraception for the duration of the study and at least one week plus 30 days (one menstrual cycle) post last dose of study drug. Exclusion Criteria: Pregnancy (positive serum or urine pregnancy test) or breastfeeding. Allergies to any member of SGLT2i class of medications. Type 2 diabetes, Maturity onset Diabetes of Young (MODY) as defined by American Diabetes Association Criteria or pancreatic disorders with resultant impaired pancreatic function. Body Mass Index > 99.9th percentile by age and sex. Presence of severe hypoglycemic event requiring assistance or glucagon rescue medication within 30 days of screening visit. Presence of documented Diabetic Ketoacidosis (DKA) within 90 days of screening visit. Current and/or anticipated adoption of a carbohydrate-restrictive diet Current eating disorder or weight loss >10% of body weight within 90 days of screening visit. Current and or/anticipated systemic corticosteroid therapy for greater than 5 days (not including inhaled, topical, eye or ear drops containing corticosteroids). Current or history of alcohol, drug or substance abuse. Participation in another drug intervention study within the past 30 days. Presence of a clinically untreated or unstable medical condition (including diagnosed Hypertension, SBP>95%) or laboratory finding that may interfere with any aspect of the study. Any concomitant medication known to interfere with the investigational product and/or renal function and/or planned study assessments based on investigators' judgement. Unable to adhere with study safety criteria, in the investigator's opinion, including a suboptimal understanding of diabetes management that would include regular and consistent blood glucose monitoring, appropriate ketone testing and DKA symptom recognition, appropriate adjustment of insulin doses for meals and activity as well as illness Participants are not allowed to change their insulin administration method (injection to pump or vice versa) throughout the study period, nor change to hybrid or closed loop insulin pumps during the study period. Known Hypersensitivity to Iohexol

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 1:1 ratio for treatment with Dapagliflozin or placebo
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention (Dapagliflozin)<br>Dapagliflozin 5mg tablet taken by mouth once daily for 16 weeks | Drug: Dapagliflozin 5mg<br>* Dapagliflozin tablet<br>* Other names: DIN: 02435462;|
| Placebo Comparator: Control (Placebo)<br>Dapagliflozin 5mg tablet taken by mouth once daily for 16 weeks | Drug: Placebo<br>* Sugar pill manufactured to mimic Dapagliflozin 5mg tablet<br>* Other names: Placebo (for Dapagliflozin);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measured Glomerular Filtration Rate (mGFR) | Change in mGFR from baseline to the end of the 16-week treatment period. | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glycated Hemoglobin A1c (HbA1c) | Change in HbA1c from baseline to the end of the 16-week treatment period. | 16 weeks | 
| Adverse events | Rate of adverse events reported from baseline to the end of the 16-week treatment period. | 16 weeks | 
| Diabetes Ketoacidosis (DKA) | Rate of confirmed DKA events from baseline to the end of the 16-week treatment period. All reported and suspected DKA events will be reviewed for confirmation by the study's DKA Adjudication Committee. | 16 weeks | 
| Hypoglycemic events | Rate of hypoglycemic events requiring assistance from baseline to the end of the 16-week treatment period. | 16 weeks | 
| Urinary and Genitourinary Tract Infections | Rate of urinary and genitourinary tract infections reported from baseline to the end of the 16-week treatment period. | 16 weeks | 
| Blood Glucose Profile | Change in ambulatory glucose profiles (AGP) from pre-drug initiation to the end of the 16-week treatment period. | 16 weeks | 
| Glycemic Variability | Change in time-in-range (TIR) from baseline to the end of the 16-week treatment period as measured by CGM. TIR is defined as the proportion of time (in %) spent with blood glucose levels between 3.9 and 10.0 mmol/L and will be determined using CGM. | 16 weeks | 
| Weight | Change in body weight (in kg) from baseline to the end of the 16-week treatment period. | 16 weeks | 
| Body Mass Index (BMI) | Change in Body Mass Index in (kg/m<sup>2</sup>) from baseline to the end of the 16-week treatment period. | 16 weeks | 
| Maturation | Assessed by Tanner pubertal staging at baseline and the end of the 16-week treatment period. | 16 weeks | 
| Total Daily Insulin Dose (TDID) | Change in the total daily dose of insulin (in IU) from baseline to the end of the 16-week treatment period. | 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dapagliflozin, Type 1 Diabetes, Adolescent, Hyperfiltration, Hyperglycemia