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

Phase 3

Active, not recruiting

• Conditions: Diabetes Mellitus, Type 1
• Interventions: Drug: Placebo; Drug: Dapagliflozin 5mg

• Registration Number: NCT04333823
• Lead Sponsor: The Hospital for Sick Children

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2020-03-30
• Study First Submitted QC: 2020-04-01
• Study First Posted: 2020-04-03
• Study Start: 2020-12-11
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-20
• Last Update Posted: 2023-11-21
• Primary Completion: 2024-05
• Study Completion: 2024-05

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

1. 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.
2. Diagnosis of Type 1 Diabetes, defined by American Diabetes Association Criteria, for at least 12 months.
3. Sex: Male and Female.
4. Age: 12 years to <19 years.
5. 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.
6. On Insulin Therapy: Daily injections, to include TID (three times a day), multiple daily dose insulin injection (MDI, > 3 injections daily) or Pump (CSII).
7. A minimum total daily dose (TDD) of insulin ≥0.6 Units/kilogram/day.
8. 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

1. Pregnancy (positive serum or urine pregnancy test) or breastfeeding.
2. Allergies to any member of SGLT2i class of medications.
3. Type 2 diabetes, Maturity onset Diabetes of Young (MODY) as defined by American Diabetes Association Criteria or pancreatic disorders with resultant impaired pancreatic function.
4. Body Mass Index > 99.9th percentile by age and sex.
5. Presence of severe hypoglycemic event requiring assistance or glucagon rescue medication within 30 days of screening visit.
6. Presence of documented Diabetic Ketoacidosis (DKA) within 90 days of screening visit.
7. Current and/or anticipated adoption of a carbohydrate-restrictive diet
8. Current eating disorder or weight loss >10% of body weight within 90 days of screening visit.
9. Current and or/anticipated systemic corticosteroid therapy for greater than 5 days (not including inhaled, topical, eye or ear drops containing corticosteroids).
10. Current or history of alcohol, drug or substance abuse.
11. Participation in another drug intervention study within the past 30 days.
12. 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.
13. Any concomitant medication known to interfere with the investigational product and/or renal function and/or planned study assessments based on investigators' judgement.
14. 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
15. 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.
16. Known Hypersensitivity to Iohexol

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control (Placebo)	Placebo	Dapagliflozin 5mg tablet taken by mouth once daily for 16 weeks
Intervention (Dapagliflozin)	Dapagliflozin 5mg	Dapagliflozin 5mg tablet taken by mouth once daily for 16 weeks

Primary Outcome Measures

Name	Time	Method
Measured Glomerular Filtration Rate (mGFR)	16 weeks	Change in mGFR from baseline to the end of the 16-week treatment period.

Secondary Outcome Measures

Name	Time	Method
Adverse events	16 weeks	Rate of adverse events reported from baseline to the end of the 16-week treatment period.
Glycated Hemoglobin A1c (HbA1c)	16 weeks	Change in HbA1c from baseline to the end of the 16-week treatment period.
Urinary and Genitourinary Tract Infections	16 weeks	Rate of urinary and genitourinary tract infections reported from baseline to the end of the 16-week treatment period.
Hypoglycemic events	16 weeks	Rate of hypoglycemic events requiring assistance from baseline to the end of the 16-week treatment period.
Diabetes Ketoacidosis (DKA)	16 weeks	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.
Blood Glucose Profile	16 weeks	Change in ambulatory glucose profiles (AGP) from pre-drug initiation to the end of the 16-week treatment period.
Glycemic Variability	16 weeks	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.
Weight	16 weeks	Change in body weight (in kg) from baseline to the end of the 16-week treatment period.
Body Mass Index (BMI)	16 weeks	Change in Body Mass Index in (kg/m\<sup\>2\</sup\>) from baseline to the end of the 16-week treatment period.
Maturation	16 weeks	Assessed by Tanner pubertal staging at baseline and the end of the 16-week treatment period.
Total Daily Insulin Dose (TDID)	16 weeks	Change in the total daily dose of insulin (in IU) from baseline to the end of the 16-week treatment period.

Trial Locations

Locations (3)

Children's Hospital Colorado Anschutz Medical Campus; 🇺🇸 Aurora, Colorado, United States

London Health Sciences Centre Children's Hospital; 🇨🇦 London, Ontario, Canada

The Hospital for Sick Children; 🇨🇦 Toronto, Ontario, Canada