Clinical trial NCT04333823: Adolescent Type 1 Diabetes Treatment With SGLT2i for hyperglycEMia & hyPerfilTration Trial
Official title: Adolescent Type 1 Diabetes Treatment With SGLT2i for hyperglycEMia & hyPerfilTration Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 1
Keywords: Dapagliflozin
Type 1 Diabetes
Adolescent
Hyperfiltration
Hyperglycemia
Lead sponsor: The Hospital for Sick Children
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
name: Juvenile Diabetes Research Foundation
First posted: 2020-04-03
Enrollment: 100
Sex: ALL
Minimum age (years): 12
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 1:1 ratio for treatment with Dapagliflozin or placebo
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Measured Glomerular Filtration Rate (mGFR)
timeFrame: 16 weeks
Secondary outcomes:
measure: Glycated Hemoglobin A1c (HbA1c)
timeFrame: 16 weeks
measure: Adverse events
timeFrame: 16 weeks
measure: Diabetes Ketoacidosis (DKA)
timeFrame: 16 weeks
measure: Hypoglycemic events
timeFrame: 16 weeks
measure: Urinary and Genitourinary Tract Infections
timeFrame: 16 weeks
measure: Blood Glucose Profile
timeFrame: 16 weeks
measure: Glycemic Variability
timeFrame: 16 weeks
measure: Weight
timeFrame: 16 weeks
measure: Body Mass Index (BMI)
timeFrame: 16 weeks
measure: Maturation
timeFrame: 16 weeks
measure: Total Daily Insulin Dose (TDID)
timeFrame: 16 weeks
Other outcomes:
measure: Flow-Mediated Dilation (FMD)
timeFrame: 16 weeks
measure: Pulse Wave Velocity (PWV)
timeFrame: 16 weeks
measure: Heart Rate Variability (HRV)
timeFrame: 16 weeks
measure: Caloric Intake
timeFrame: 16 weeks
measure: Macronutrient Intake
timeFrame: 16 weeks
measure: Treatment Satisfaction
timeFrame: 16 weeks
measure: Diabetes Management
timeFrame: 16 weeks
measure: BOLD MRI
timeFrame: 16 weeks
measure: Exercise Session - Blood Glucose Levels
timeFrame: 4 weeks
measure: Exercise Session - Blood Glucose Variability
timeFrame: 4 weeks
Locations:
city: Aurora
country: United States
facility: Children's Hospital Colorado Anschutz Medical Campus
state: Colorado
city: London
country: Canada
facility: London Health Sciences Centre Children's Hospital
state: Ontario
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
Study officials:
affiliation: The Hospital for Sick Children
name: Farid H Mahmud, MD
role: PRINCIPAL_INVESTIGATOR
References: