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

Type 1 Diabetes Clinical Trial

Official title:

Effect of Canagliflozin in T1DM After Interruption of Continuous Subcutaneous Insulin Infusion

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02673138
• Other study ID #: 1508016333
• Secondary ID: 1K12DK094714-01
• Status: Completed
• Phase: N/A
• Start date: January 2016
• Est. completion date: July 2017

Study information

• Verified date: September 2021
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: July 2017
• Est. primary completion date: January 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 1
• Type 1 Diabetes

Intervention

Drug:
• canagliflozin
basal interruption with canagliflozin

Other:
• basal interruption without canagliflozin
basal interruption

Locations

Country	Name	City	State
United States	Yale University School of Medicine	New Haven	Connecticut

Sponsors (2)

Lead Sponsor	Collaborator
Yale University	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Differences in Plasma Glucose Levels Following the Interruption of Basal Subcutaneous Infusion of Insulin	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.	20 hours
Primary	Differences in BHB (Beta-hydroxybutyrate) Levels Following Interruption of Basal		20 hours
Secondary	Differences in Free Fatty Acid Levels Following Interruption of Basal Subcutaneous Insulin Infusion		20 hours
Secondary	Differences in Glucagon Levels Following the Interruption of the Basal Subcutaneous Insulin Infusion		20 hours