Clinical trial NCT02673138: Effect of Canagliflozin in T1DM (Type 1 Diabetes Melitus) After Interruption of Continuous Subcutaneous Insulin Infusion
Official title: Effect of Canagliflozin in T1DM After Interruption of Continuous Subcutaneous Insulin Infusion
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type 1 Diabetes
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2016-02-03
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

Eligibility criteria: 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

Primary outcomes:
measure: Differences in Plasma Glucose Levels Following the Interruption of Basal Subcutaneous Infusion of Insulin
timeFrame: 20 hours
measure: Differences in BHB (Beta-hydroxybutyrate) Levels Following Interruption of Basal
timeFrame: 20 hours
Secondary outcomes:
measure: Differences in Free Fatty Acid Levels Following Interruption of Basal Subcutaneous Insulin Infusion
timeFrame: 20 hours
measure: Differences in Glucagon Levels Following the Interruption of the Basal Subcutaneous Insulin Infusion
timeFrame: 20 hours
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
Study officials:
affiliation: Yale University
name: Neha Patel, DO
role: PRINCIPAL_INVESTIGATOR
References: