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

• Sponsor: Yale University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02673138
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)
• Enrollment: 10
• Location: 1
• Arms: 2
• Duration (Months): 18
• Patients Per Site Per Month: 0.6

Study Details

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	N/A

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
• 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: Jan 1, 2016
• Actual Primary Completion Date: Jan 1, 2017
• Actual Study Completion Date: Jul 1, 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 Names: Invokana

Outcome Measures

Primary Outcome Measures

1. 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.

2. Differences in BHB (Beta-hydroxybutyrate) Levels Following Interruption of Basal [20 hours]

Secondary Outcome Measures

1. Differences in Free Fatty Acid Levels Following Interruption of Basal Subcutaneous Insulin Infusion [20 hours]

2. Differences in Glucagon Levels Following the Interruption of the Basal Subcutaneous Insulin Infusion [20 hours]

Eligibility Criteria

Criteria

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

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

3. History of unstable or rapidly progressing renal disease

4. Conditions of congenital renal glucosuria

5. Renal allograft

6. Recurrent UTI (urinary tract infection)

7. History of Vesico-ureteral-reflux disease

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

9. 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

10. 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

11. History of hypoglycemic seizure within last 3 months

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

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

14. 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

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

16. Recurrent GU (genitourinary) infections

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

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT02673138
• Other Study ID Numbers: 1508016333; 1K12DK094714-01
• First Posted: Feb 3, 2016
• Last Update Posted: Oct 13, 2021
• Last Verified: Sep 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Diabetes Mellitus, Type 1; Canagliflozin

Study Results

Participant Flow

Arm/Group Title	Basal Interruption With or Without Canagliflozin
Arm/Group Description	Subjects will undergo basal interruption with or without canagliflozin during an overnight stay on the research unit canagliflozin: basal interruption with canagliflozin
Period Title: Overall Study
STARTED	10
Started Day 1	10
Ended Day 1	10
Started Day 2	10
Ended Day 2	10
COMPLETED	10
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Basal Interruption With or Without Canagliflozin
Arm/Group Description	Subjects will undergo basal interruption with canagliflozin during an overnight stay on the research unit canagliflozin: basal interruption with canagliflozin
Overall Participants	10
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	10 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	8 80%
Male	2 20%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Basal Interruption	Basal Interruption With Canagliflozin
Arm/Group Description	Subjects will undergo basal interruption without canagliflozin during an overnight stay on the research unit basal interruption without canagliflozin: basal interruption	Subjects will undergo basal interruption with canagliflozin during an overnight stay on the research unit canagliflozin: basal interruption with canagliflozin
Measure Participants	10	10
Mean (Standard Error) [mg/dL]	197 (24)	99 (13)

2. Primary Outcome

Title	Differences in BHB (Beta-hydroxybutyrate) Levels Following Interruption of Basal
Time Frame	20 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Basal Interruption	Basal Interruption With Canagliflozin
Arm/Group Description	Subjects will undergo basal interruption without canagliflozin during an overnight stay on the research unit basal interruption without canagliflozin: basal interruption	Subjects will undergo basal interruption with canagliflozin during an overnight stay on the research unit canagliflozin: basal interruption with canagliflozin
Measure Participants	10	10
Mean (Standard Error) [mmol/L]	1.2 (0.2)	1.5 (0.2)

3. Secondary Outcome

Title	Differences in Free Fatty Acid Levels Following Interruption of Basal Subcutaneous Insulin Infusion
Time Frame	20 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Basal Interruption	Basal Interruption With Canagliflozin
Arm/Group Description	Subjects will undergo basal interruption without canagliflozin during an overnight stay on the research unit basal interruption without canagliflozin: basal interruption	Subjects will undergo basal interruption with canagliflozin during an overnight stay on the research unit canagliflozin: basal interruption with canagliflozin
Measure Participants	10	10
Mean (Standard Error) [mmol/L]	0.8 (0.1)	0.7 (0.1)

4. Secondary Outcome

Title	Differences in Glucagon Levels Following the Interruption of the Basal Subcutaneous Insulin Infusion
Time Frame	20 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Basal Interruption	Basal Interruption With Canagliflozin
Arm/Group Description	Subjects will undergo basal interruption without canagliflozin during an overnight stay on the research unit basal interruption without canagliflozin: basal interruption	Subjects will undergo basal interruption with canagliflozin during an overnight stay on the research unit canagliflozin: basal interruption with canagliflozin
Measure Participants	10	10
Mean (Standard Error) [pg/mL]	14 (5)	36 (15)

Adverse Events

Arm/Group Title	Basal Interruption		Basal Interruption With Canagliflozin
Arm/Group Description	Subjects will undergo basal interruption without canagliflozin during an overnight stay on the research unit basal interruption without canagliflozin: basal interruption		Subjects will undergo basal interruption with canagliflozin during an overnight stay on the research unit canagliflozin: basal interruption with canagliflozin
All Cause Mortality
	Basal Interruption		Basal Interruption With Canagliflozin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)
Serious Adverse Events
	Basal Interruption		Basal Interruption With Canagliflozin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	Basal Interruption		Basal Interruption With Canagliflozin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		1/10 (10%)
Infections and infestations
Vaginal Candidiasis	0/10 (0%)	0	1/10 (10%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.