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

• ClinicalTrials.gov Identifier: NCT02673138
• Recruitment Status: Completed
• First Posted: February 3, 2016
• Results First Posted: November 29, 2018
• Last Update Posted: October 13, 2021
• Sponsor: Yale University
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Information provided by (Responsible Party): Yale University

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.

Condition or disease	Intervention/treatment	Phase
Type 1 Diabetes	Drug: canagliflozin; Other: basal interruption without canagliflozin	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 10 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Effect of Canagliflozin in T1DM After Interruption of Continuous Subcutaneous Insulin Infusion
• Study Start Date: January 2016
• Actual Primary Completion Date: January 2017
• Actual Study Completion Date: July 2017

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Basal interruption; Subjects will undergo basal interruption without canagliflozin during an overnight stay on the research unit	Other: basal interruption without canagliflozin; basal interruption
Experimental: Basal interruption with canagliflozin; Subjects will undergo basal interruption with canagliflozin during an overnight stay on the research unit	Drug: canagliflozin; basal interruption with canagliflozin; Other Name: Invokana

Outcome Measures

Primary Outcome Measures :

1. Differences in Plasma Glucose Levels Following the Interruption of Basal Subcutaneous Infusion of Insulin [ Time Frame: 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.
2. Differences in BHB (Beta-hydroxybutyrate) Levels Following Interruption of Basal [ Time Frame: 20 hours ]

Secondary Outcome Measures :

1. Differences in Free Fatty Acid Levels Following Interruption of Basal Subcutaneous Insulin Infusion [ Time Frame: 20 hours ]
2. Differences in Glucagon Levels Following the Interruption of the Basal Subcutaneous Insulin Infusion [ Time Frame: 20 hours ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Connecticut

Yale University School of Medicine

New Haven, Connecticut, United States, 06520

Sponsors and Collaborators

Yale University

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

• Principal Investigator: Neha Patel, DO; Yale University

More Information

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT02673138
• Other Study ID Numbers: 1508016333; 1K12DK094714-01 ( U.S. NIH Grant/Contract )
• First Posted: February 3, 2016
• Results First Posted: November 29, 2018
• Last Update Posted: October 13, 2021
• Last Verified: September 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Additional relevant MeSH terms:

Diabetes Mellitus, Type 1; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Canagliflozin; Sodium-Glucose Transporter 2 Inhibitors; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Physiological Effects of Drugs