Effect of Canagliflozin in T1DM (Type 1 Diabetes Melitus) After Interruption of Continuous Subcutaneous Insulin Infusion
Primary Purpose
Type 1 Diabetes
Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
canagliflozin
basal interruption without canagliflozin
Sponsored by
About this trial
This is an interventional treatment trial for Type 1 Diabetes
Eligibility Criteria
Inclusion Criteria:
- Age 18-45 years
- Clinical diagnosis of T1D (type 1 diabetes) (formal antibody and/or genetic testing will not be required)
- Duration of T1D ≥ 1 year
- HbA1c ≤ 9 %
- Treated with continuous subcutaneous insulin infusion (with or without adjunctive treatment with a SGLT2 inhibitor) for at least 3 months
- Body weight > 40 kg
- 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
- Normal hematocrit
- Able to give consent
- Female subjects of reproductive potential must be abstinent or consistently using appropriate family planning methods.
Exclusion Criteria:
- Insulin resistant (defined as requiring > 1.5 units/kg/day at time of study enrollment)
Renal impairment, determined as eGFR < 60 ml/minute/1.73m2
- History of unstable or rapidly progressing renal disease
- Conditions of congenital renal glucosuria
- Renal allograft
- Recurrent UTI (urinary tract infection)
- History of Vesico-ureteral-reflux disease
- Presence of any medical or psychiatric disorder that may interfere with subject safety or study conduct
- 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
- 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
- History of hypoglycemic seizure within last 3 months
- History of diabetic ketoacidosis (DKA) requiring medical intervention (ie. emergency room visit and/or hospitalization) within 1 month prior to the screening visit
- Allergies or contraindication to the contents of canagliflozin tablets or insulin
- 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
- Female subjects who are pregnant, lactating, or unwilling to be tested for pregnancy
- Recurrent GU (genitourinary) infections
- Uncircumcised males secondary to increased risk of development of GU infections
- History of hypotension, defined as blood pressure (BP) <10th% for age and sex
Sites / Locations
- Yale University School of Medicine
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Basal interruption
Basal interruption with canagliflozin
Arm Description
Subjects will undergo basal interruption without canagliflozin during an overnight stay on the research unit
Subjects will undergo basal interruption with canagliflozin during an overnight stay on the research unit
Outcomes
Primary Outcome Measures
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.
Differences in BHB (Beta-hydroxybutyrate) Levels Following Interruption of Basal
Secondary Outcome Measures
Differences in Free Fatty Acid Levels Following Interruption of Basal Subcutaneous Insulin Infusion
Differences in Glucagon Levels Following the Interruption of the Basal Subcutaneous Insulin Infusion
Full Information
NCT ID
NCT02673138
First Posted
February 1, 2016
Last Updated
September 17, 2021
Sponsor
Yale University
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
1. Study Identification
Unique Protocol Identification Number
NCT02673138
Brief Title
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
2. Study Status
Record Verification Date
September 2021
Overall Recruitment Status
Completed
Study Start Date
January 2016 (undefined)
Primary Completion Date
January 2017 (Actual)
Study Completion Date
July 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Yale University
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
4. Oversight
Data Monitoring Committee
No
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 1 Diabetes
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Basal interruption
Arm Type
Active Comparator
Arm Description
Subjects will undergo basal interruption without canagliflozin during an overnight stay on the research unit
Arm Title
Basal interruption with canagliflozin
Arm Type
Experimental
Arm Description
Subjects will undergo basal interruption with canagliflozin during an overnight stay on the research unit
Intervention Type
Drug
Intervention Name(s)
canagliflozin
Other Intervention Name(s)
Invokana
Intervention Description
basal interruption with canagliflozin
Intervention Type
Other
Intervention Name(s)
basal interruption without canagliflozin
Intervention Description
basal interruption
Primary Outcome Measure Information:
Title
Differences in Plasma Glucose Levels Following the Interruption of Basal Subcutaneous Infusion of Insulin
Description
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.
Time Frame
20 hours
Title
Differences in BHB (Beta-hydroxybutyrate) Levels Following Interruption of Basal
Time Frame
20 hours
Secondary Outcome Measure Information:
Title
Differences in Free Fatty Acid Levels Following Interruption of Basal Subcutaneous Insulin Infusion
Time Frame
20 hours
Title
Differences in Glucagon Levels Following the Interruption of the Basal Subcutaneous Insulin Infusion
Time Frame
20 hours
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age 18-45 years
Clinical diagnosis of T1D (type 1 diabetes) (formal antibody and/or genetic testing will not be required)
Duration of T1D ≥ 1 year
HbA1c ≤ 9 %
Treated with continuous subcutaneous insulin infusion (with or without adjunctive treatment with a SGLT2 inhibitor) for at least 3 months
Body weight > 40 kg
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
Normal hematocrit
Able to give consent
Female subjects of reproductive potential must be abstinent or consistently using appropriate family planning methods.
Exclusion Criteria:
Insulin resistant (defined as requiring > 1.5 units/kg/day at time of study enrollment)
Renal impairment, determined as eGFR < 60 ml/minute/1.73m2
History of unstable or rapidly progressing renal disease
Conditions of congenital renal glucosuria
Renal allograft
Recurrent UTI (urinary tract infection)
History of Vesico-ureteral-reflux disease
Presence of any medical or psychiatric disorder that may interfere with subject safety or study conduct
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
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
History of hypoglycemic seizure within last 3 months
History of diabetic ketoacidosis (DKA) requiring medical intervention (ie. emergency room visit and/or hospitalization) within 1 month prior to the screening visit
Allergies or contraindication to the contents of canagliflozin tablets or insulin
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
Female subjects who are pregnant, lactating, or unwilling to be tested for pregnancy
Recurrent GU (genitourinary) infections
Uncircumcised males secondary to increased risk of development of GU infections
History of hypotension, defined as blood pressure (BP) <10th% for age and sex
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Neha Patel, DO
Organizational Affiliation
Yale University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Yale University School of Medicine
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Effect of Canagliflozin in T1DM (Type 1 Diabetes Melitus) After Interruption of Continuous Subcutaneous Insulin Infusion
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