Effect of Canagliflozin in T1DM (Type 1 Diabetes Melitus) After Interruption of Continuous Subcutaneous Insulin Infusion

Not Applicable

Completed

• Conditions: Type 1 Diabetes
• Interventions: Other: basal interruption without canagliflozin; Drug: canagliflozin

• Registration Number: NCT02673138
• Lead Sponsor: Yale University

Brief Summary

This study will be an open-label, cross-over study as subjects will be studied under both study conditions - suspension of subcutaneous insulin infusion via pump during treatment with insulin alone (control) vs. suspension of subcutaneous insulin via pump during treatment with insulin and canagliflozin.

Detailed Description

The study will consist of 4 visits: an enrollment/screening visit, a control visit with pump suspension prior to treatment with canagliflozin, a visit with pump suspension while on canagliflozin and an end of study visit. Each of the pump suspension visits will be approximately 20-hour overnight admissions to the Hospital Research Unit (HRU).

Study Timeline

• Study Start: 2016-01
• Study First Submitted: 2016-02-01
• Study First Submitted QC: 2016-02-01
• Study First Posted: 2016-02-03
• Primary Completion: 2017-01
• Study Completion: 2017-07
• Results First Submitted: 2018-11-01
• Results First Submitted QC: 2018-11-01
• Results First Posted: 2018-11-29
• Status Verified: 2021-09
• Last Update Submitted: 2021-09-17
• Last Update Posted: 2021-10-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

1. Age 18-45 years
2. Clinical diagnosis of T1D (type 1 diabetes) (formal antibody and/or genetic testing will not be required)
3. Duration of T1D ≥ 1 year
4. HbA1c ≤ 9 %
5. Treated with continuous subcutaneous insulin infusion (with or without adjunctive treatment with a SGLT2 inhibitor) for at least 3 months
6. Body weight > 40 kg
7. Be in good general health without other acute or chronic illness that in the judgment of the investigator could interfere with the study or jeopardize subject safety
8. Normal hematocrit
9. Able to give consent
10. Female subjects of reproductive potential must be abstinent or consistently using appropriate family planning methods.

Exclusion Criteria

1. Insulin resistant (defined as requiring > 1.5 units/kg/day at time of study enrollment)

2. Renal impairment, determined as eGFR < 60 ml/minute/1.73m2

   1. History of unstable or rapidly progressing renal disease
   2. Conditions of congenital renal glucosuria
   3. Renal allograft
   4. Recurrent UTI (urinary tract infection)
   5. History of Vesico-ureteral-reflux disease

3. Presence of any medical or psychiatric disorder that may interfere with subject safety or study conduct

4. Use of metformin, thiazolidinedione or GLP1 agonist within 1 month prior to screening visit. For those subjects on canagliflozin or other SGLT2 inhibitors, an alternate study procedure may be utilized as described above

5. Use of any medications (besides insulin or SGLT2 inhibitor) known to effect blood glucose levels, including oral or other systemic glucocorticoid therapy. Inhaled, intranasal, or rectal corticosteroid use is allowed as long as not given within 2 weeks of the closed loop admissions. Use of topical glucocorticoids is allowable as long as affected skin area does not overlap with study device sites

6. History of hypoglycemic seizure within last 3 months

7. History of diabetic ketoacidosis (DKA) requiring medical intervention (ie. emergency room visit and/or hospitalization) within 1 month prior to the screening visit

8. Allergies or contraindication to the contents of canagliflozin tablets or insulin

9. Volume depleted subjects. Subjects at risk for volume depletion due to co-existing conditions or concomitant medications, such as loop diuretics who cannot carefully monitor their volume status should be excluded from the study

10. Female subjects who are pregnant, lactating, or unwilling to be tested for pregnancy

11. Recurrent GU (genitourinary) infections

12. Uncircumcised males secondary to increased risk of development of GU infections

13. History of hypotension, defined as blood pressure (BP) <10th% for age and sex

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Basal interruption	basal interruption without canagliflozin	Subjects will undergo basal interruption without canagliflozin during an overnight stay on the research unit
Basal interruption with canagliflozin	canagliflozin	Subjects will undergo basal interruption with canagliflozin during an overnight stay on the research unit

Primary Outcome Measures

Name	Time	Method
Differences in Plasma Glucose Levels Following the Interruption of Basal Subcutaneous Infusion of Insulin	20 hours	The primary outcome measure for this study will be differences in plasma glucose levels following the interruption of basal subcutaneous infusion of insulin under the two study conditions; i.e., control study during treatment with insulin alone vs. experimental study during treatment with insulin plus canagliflozin or other SGLT2 inhibitor.
Differences in BHB (Beta-hydroxybutyrate) Levels Following Interruption of Basal	20 hours

Secondary Outcome Measures

Name	Time	Method
Differences in Free Fatty Acid Levels Following Interruption of Basal Subcutaneous Insulin Infusion	20 hours
Differences in Glucagon Levels Following the Interruption of the Basal Subcutaneous Insulin Infusion	20 hours

Trial Locations

Locations (1)

Yale University School of Medicine; 🇺🇸 New Haven, Connecticut, United States