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

Diabetes Mellitus, Type 1 Clinical Trial

— ATTEMPT  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04333823
• Other study ID #: CTO1940
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 11, 2020
• Est. completion date: May 2024

Study information

• Verified date: November 2023
• Source: The Hospital for Sick Children
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 100
• Est. completion date: May 2024
• Est. primary completion date: May 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Hyperglycemia

Intervention

Drug:
• Dapagliflozin 5mg
Dapagliflozin tablet
• Placebo
Sugar pill manufactured to mimic Dapagliflozin 5mg tablet

Locations

Country	Name	City	State
Canada	London Health Sciences Centre Children's Hospital	London	Ontario
Canada	The Hospital for Sick Children	Toronto	Ontario
United States	Children's Hospital Colorado Anschutz Medical Campus	Aurora	Colorado

Sponsors (3)

Lead Sponsor	Collaborator
The Hospital for Sick Children	Canadian Institutes of Health Research (CIHR), Juvenile Diabetes Research Foundation

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Flow-Mediated Dilation (FMD)	Change in flow mediated dilation using high resolution ultrasound from baseline to the end of the 16-week treatment period.	16 weeks
Other	Pulse Wave Velocity (PWV)	Change in pulse pressure waveforms from baseline to the end of the 16-week treatment period.	16 weeks
Other	Heart Rate Variability (HRV)	Change in heart rate variability from baseline to the end of the 16-week treatment period.	16 weeks
Other	Caloric Intake	Change in daily caloric intake (in kcals) from baseline to the end of the 16-week treatment period.	16 weeks
Other	Macronutrient Intake	Change in daily macronutrient intake (carbohydrates, fat, protein) in grams per kcals from baseline to the end of the 16-week treatment period.	16 weeks
Other	Treatment Satisfaction	Assessed using the Diabetes Treatment Satisfaction Questionnaire (DTSQ), using a standardized scoring system.	16 weeks
Other	Diabetes Management	Assessed using the Diabetes Management Questionnaire (DMQ) using a 20 item questionnaire with standardized scoring.	16 weeks
Other	BOLD MRI	Changes in functional renal imaging	16 weeks
Other	Exercise Session - Blood Glucose Levels	Change in blood glucose levels from pre- to post-exercise from baseline to 4 weeks post-drug initiation. Participants in the optional exercise component will undergo a moderate activity exercise session and will have their blood tested before and at the end of the 60-minute session.	4 weeks
Other	Exercise Session - Blood Glucose Variability	Change in time-in-range (TIR) during a moderate activity exercise session from baseline to 4 weeks post-drug initiation. 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.	4 weeks
Primary	Measured Glomerular Filtration Rate (mGFR)	Change in mGFR from baseline to the end of the 16-week treatment period.	16 weeks
Secondary	Glycated Hemoglobin A1c (HbA1c)	Change in HbA1c from baseline to the end of the 16-week treatment period.	16 weeks
Secondary	Adverse events	Rate of adverse events reported from baseline to the end of the 16-week treatment period.	16 weeks
Secondary	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
Secondary	Hypoglycemic events	Rate of hypoglycemic events requiring assistance from baseline to the end of the 16-week treatment period.	16 weeks
Secondary	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
Secondary	Blood Glucose Profile	Change in ambulatory glucose profiles (AGP) from pre-drug initiation to the end of the 16-week treatment period.	16 weeks
Secondary	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
Secondary	Weight	Change in body weight (in kg) from baseline to the end of the 16-week treatment period.	16 weeks
Secondary	Body Mass Index (BMI)	Change in Body Mass Index in (kg/m	16 weeks
Secondary	Maturation	Assessed by Tanner pubertal staging at baseline and the end of the 16-week treatment period.	16 weeks
Secondary	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