RISING-STAR study

JRCT ID: jRCTs051190114

Registered date:02/03/2020

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: type 1 diabetes mellitus
• Date of first enrollment: 04/03/2020
• Target sample size: 60
• Study type: Interventional

Intervention(s)

[Group A] The study subjects are instructed to reduce basal insulin dose 0% (instructed to reduce bolus insulin dose)
Group of the study subjects whose Basal/TDD is less than 0.4. The study subjects are instructed not to reduce basal insulin dose but to reduce bolus insulin dose 10%. The 10% reduction of the bolus insulin dose is instructed by setting CIR to 90%, and the bolus insulin dose is instructed by rounding down the second decimal place of the calculated bolus insulin dose. The study subjects obey the instruction for 3 days after the start of the intervention in principal, and titrate basal and bolus insulin dose by themselves and by the instruction from the attending physician according to "7.6.2. Algorism for Basal Insulin Titration after SGLT2 administration" and "7.6.3. Algorism for Bolus Insulin Titration after SGLT2 administration" from days 4.

[Group B] The study subjects are instructed to reduce basal insulin 10%
Group of the study subjects whose Basal/TDD is 0.4 or higher. The study subjects are instructed to reduce total insulin dose 10% by reducing from basal insulin dose. The units of total insulin dose reduction is instructed by rounding down the first decimal place of calculated 10% of total insulin dose, or rounding up the second decimal place of basal insulin rate in CSII. The study subjects obey the instruction for 3 days after the start of the intervention in principal, and titrate basal and bolus insulin dose by themselves and by the instruction from the attending physician according to "7.6.2. Algorism for Basal Insulin Titration" and "7.6.3. Algorism for Bolus Insulin Titration" from days 4.

Outcome(s)

• Primary Outcome: Frequency of hypoglycemia per day confirmed by self-monitoring of blood glucose (SMBG) during intervention period (administration of SGLT2 inhibitor) (number of hypoglycemia/day)

Secondary Outcome

1. Frequency of ketosis before and after the intervention
Ketosis is defined as plasma beta-hydroxybutyric acid is 600 micromol/L or higher when measured at home or at the research institutions. Frequency of ketosis is defined as the proportion of number of days in which the ketosis occurs in the study subjects during the pre-observation period and the observation period after the intervention.
2. Frequency of hypoglycemia per day before and after the intervention detected by FGM (number of hypoglycemia/day)
3. Change and difference in change between the intervention groups in following items before and after the intervention
- fasting plasma beta-hydroxybutyric acid (ketone body)
- basal insulin dose*, bolus insulin dose*, total insulin dose*, Carbohydrate Insulin Ratio (CIR), Insulin Sensitivity Factor (ISF)
- time of hypoglycemia (percentage of time spent in glucose range =< 70mg/dl), time of hyperglycemia (percentage of time spent in glucose range >= 70mg/dl) time of nocturnal hypoglycemia, detected by FGM
- Vital sign / blood pressure, pulse rate
- body weight, BMI, skeletal muscle mass**, fat mass**
- blood biomarker / red blood cell count, white blood cell count, hemoglobin, hematocrit, blood platelet count, hepatic enzymes (AST, ALT, LDH, ALP, gamma-GTP), UA, T-Chol, HDL, LDL, TG, BUN, Cre, eGFR, BNP**, HbA1c (or glycoalbumin), plasma glucose, serum albumin, CPR**, CPR index**
- urine biomarker / specific gravity, pH, protein, glucose, ketone body, occult blood, urobilinogen, bilirubin, u-mAlb, U-Cre, U-mAlb/Cre ratio
- total ketone body**, beta-hydroxybutyric acid**, acetoacetic acid**
- QOL score (DTSQ)
*measured by daily dose
**measured at visit 2 and 4 only

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: < 80age old
• Gender: Both

Include criteria

Patients who meet all of the following criteria are included in this study:
1. Outpatients in the research institutions in this study who are diagnosed as type 1 diabetes mellitus before 6 months or more of giving their consent
2. Patients who have conducted the intensive insulin therapy for 1 year or longer
3. Patients who are well educated in carbohydrate counting, and who can conduct insulin self-titration
4. Patients with good understanding of the disease and capability to recognize DKA (symptoms and use of ketone meter)
5. Male and female aged 20 years or older and younger than 80 years when giving their consent
6. Patients who provide their consent in a written form

Exclude criteria

Patients who fall into any of the following criteria are excluded from participating in the study. The clinical laboratory values which are the latest and obtained within 3 months before obtaining their consent are used to judge the exclusion criteria:
1. Patients who use SGLT2 inhibitor at giving their content
2. Patients whose eGFR is less than 45 ml/min/1.73m2
3. Patients whose activities of daily living (ADL) is PS2 or higher
4. Patients with dementia or cognitive impairment
5. Patients whose BMI is less than 18.5 kg/m2
6. Patients with history of ketoacidosis within 3 months before giving their consent
7. Patients with history of Cardiovascular disease (myocardial infarction, heart failure, angina pectoris) within 3 months before giving their consent
8. Patients whose HbA1c is 10.5% or higher
9. Patients who had hypoglycemia 14 times or more within 4 weeks before giving their consent
10. Patients with anemia (male: Hb is 13 g/dL or less, female: Hb is 12 g/dL or less), hypoalbuminemia (serum albumin is 3.5 g/dL or less), or nephrotic syndrome (urinary protein is 3.5 g/day or more, and serum albumin is 3.0 g/dL or less) caused by primary diseases other than diabetic nephropathy
11. Patients who are breastfeeding, pregnant, possibly pregnant, or planning to be pregnant
12. Patients with cancer. However, those who have completed treatment and/or show no redevelopment of cancer, as well as manifest some degree of remission can be considered to be participants of this study
13. Patients who meet the contraindication of the study agent
14. Patients who are conducting diet therapy with carbohydrate of less than 40%
15. Patients with poor adherence judged by the attending physician
16. Patients with other conditions that the responsible investigator/subinvestigator thinks inappropriate to participate in the study

Related Information

• Primary Sponsor: Yamazaki Masahiro
• Source(s) of Monetary Support: AstraZeneca K.K.