SGLT2 Inhibitor Adjunctive Therapy to Closed Loop Control in Type 1 Diabetes Mellitus

NCT ID: NCT04201496

Last Updated: 2022-08-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-24
• Study Completion Date: 2021-09-07

Brief Summary

The primary purpose of this study is to evaluate the safety and efficacy of combining SGLT2 inhibitors with closed loop control (CLC).

Detailed Description

The first five participants will be enrolled in a Pilot Study to use the Basal-IQ with Empagliflozin 10 mg daily for approximately two weeks. These participants will participate in an estimated 36-48-hour hotel admission to initiate use of Closed Loop Control. The safety data from the Pilot Study will be presented to the Data Safety Monitoring Board (DSMB) for review.

Upon DSMB approval, approximately 40 participants will be randomized 1:1 in a crossover design. Participants will use empagliflozin 5 mg daily. This main study is a randomized control trial where approximately 50 participants, aged 18 to less than 65 y.o. at time of consent, will be in the trial for up to 10 weeks.

With empagliflozin:

• Control-IQ (CiQ) x 4 weeks (CiQ-EMPA) then Basal-IQ x 2 weeks (BiQ-EMPA)
• Basal-IQ x 2 weeks (BiQ-EMPA) then CiQ x 4 weeks (CiQ-EMPA)

Without empagliflozin:

• CiQ x 4 weeks (CiQ-NO EMPA) then Basal-IQ x 2 weeks (BiQ-NO EMPA)
• Basal-IQ x 2 weeks (BiQ-NO EMPA) then CiQ x 4 weeks (CiQ-NO EMPA)

Conditions

Type 1 Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Empagliflozin + Control-IQ x 4 wks then Basal-IQ x 2 wks

Control-IQ x 4 weeks (CiQ-EMPA) then Basal-IQ x 2 weeks (BiQ-EMPA)

Group Type: EXPERIMENTAL

Empagliflozin + Control-IQ x 4 wks then Basal-IQ x 2 wks

Intervention Type: COMBINATION_PRODUCT

Participants with be provided with Empagliflozin to take daily for approximately 10 weeks. Along with the study medication, participants will initially use the Tandem t:slim insulin pump with Control-IQ Technology for 4 weeks. Participants will then transition to using the Tandem t:slim insulin pump with Basal-IQ Technology for 2 weeks.

Empagliflozin + Basal-IQ x 2 wks then CiQ x 4 wks

Basal-IQ x 2 weeks (BiQ-EMPA) then Control-IQ x 4 weeks (CiQ-EMPA)

Group Type: EXPERIMENTAL

Empagliflozin + Basal-IQ x 2 wks then Control-IQ x 4 wks

Intervention Type: COMBINATION_PRODUCT

Participants with be provided with Empagliflozin to take daily for approximately 10 weeks. Along with the study medication, participants will initially use the Tandem t:slim insulin pump with Basal-IQ Technology for 2 weeks. Participants will then transition to using the Tandem t:slim insulin pump with Control-IQ Technology for 4 weeks.

No Empagliflozin + Control-IQ x 4 wks then Basal-IQ x 2 wks

Control-IQ x 4 weeks (CiQ-NO EMPA) then Basal-IQ x 2 weeks (BiQ-NO EMPA)

Group Type: ACTIVE_COMPARATOR

No Empagliflozin + Control-IQ x 4 wks then Basal-IQ x 2 wks

Intervention Type: DEVICE

Participants will initially use the Tandem t:slim insulin pump with Control-IQ Technology for 4 weeks. Participants will then transition to using the Tandem t:slim insulin pump with Basal-IQ Technology for 2 weeks. Empaglizflozin will not be provided to this group.

No Empagliflozin + Basal-IQ x 2 wks then Control-IQ x 4 wks

Basal-IQ x 2 weeks (BiQ-NO EMPA) then Control-IQ x 4 weeks (CiQ-NO EMPA)

Group Type: ACTIVE_COMPARATOR

No Empagliflozin + Basal-IQ x 2 wks then Control-IQ x 4 wks

Intervention Type: DEVICE

Participants will initially use the Tandem t:slim insulin pump with Basal-IQ Technology for 2 weeks. Participants will then transition to using the Tandem t:slim insulin pump with Control-IQ Technology for 4 weeks. Empaglizflozin will not be provided to this group.

Interventions

Empagliflozin + Control-IQ x 4 wks then Basal-IQ x 2 wks

Participants with be provided with Empagliflozin to take daily for approximately 10 weeks. Along with the study medication, participants will initially use the Tandem t:slim insulin pump with Control-IQ Technology for 4 weeks. Participants will then transition to using the Tandem t:slim insulin pump with Basal-IQ Technology for 2 weeks.

Intervention Type: COMBINATION_PRODUCT

Empagliflozin + Basal-IQ x 2 wks then Control-IQ x 4 wks

Participants with be provided with Empagliflozin to take daily for approximately 10 weeks. Along with the study medication, participants will initially use the Tandem t:slim insulin pump with Basal-IQ Technology for 2 weeks. Participants will then transition to using the Tandem t:slim insulin pump with Control-IQ Technology for 4 weeks.

Intervention Type: COMBINATION_PRODUCT

No Empagliflozin + Control-IQ x 4 wks then Basal-IQ x 2 wks

Participants will initially use the Tandem t:slim insulin pump with Control-IQ Technology for 4 weeks. Participants will then transition to using the Tandem t:slim insulin pump with Basal-IQ Technology for 2 weeks. Empaglizflozin will not be provided to this group.

Intervention Type: DEVICE

No Empagliflozin + Basal-IQ x 2 wks then Control-IQ x 4 wks

Participants will initially use the Tandem t:slim insulin pump with Basal-IQ Technology for 2 weeks. Participants will then transition to using the Tandem t:slim insulin pump with Control-IQ Technology for 4 weeks. Empaglizflozin will not be provided to this group.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

1. Age ≥18.0 and ≤65 years old at time of consent

2. Clinical diagnosis, based on investigator assessment, of type 1 diabetes for at least one year

3. Currently using an insulin pump for at least six months

4. Currently using insulin for at least six months

5. Using insulin parameters such as carbohydrate ratio and correction factors consistently on their pump in order to dose insulin for meals or corrections

6. Access to internet and willingness to upload data during the study as needed

7. For females, not currently known to be pregnant or breastfeeding

8. If female and sexually active, must agree to use a form of contraception to prevent pregnancy while a participant in the study. A negative serum or urine pregnancy test will be required for all females of childbearing potential. Participants who become pregnant will be discontinued from the study. Also, participants who during the study develop and express the intention to become pregnant within the timespan of the study will be discontinued.

9. Willingness to suspend use of any personal CGM for the duration of the clinical trial once the study CGM is in use

10. Willingness to switch to lispro (Humalog) or aspart (Novolog) if not using already, and to use no other insulin besides lispro (Humalog) or aspart (Novolog) during the study

11. Total daily insulin dose (TDD) at least 10 U/day

12. Willingness not to start any new non-insulin glucose-lowering agent during the course of the trial (including metformin, GLP-1 agonists, pramlintide, DPP-4 inhibitors, biguanides, sulfonylureas and naturaceuticals)

13. Willingness to eat at least 100 grams of carbohydrates per day

14. An understanding and willingness to follow the protocol and signed informed consent

15. Pilot Participants: Agree to hotel/research house admission with other Pilot participants on a date selected by the study team.

Exclusion Criteria

1. Hemoglobin A1c >9%

2. History of diabetic ketoacidosis (DKA) in the 12 months prior to enrollment

3. Severe hypoglycemia resulting in seizure or loss of consciousness in the 12 months prior to enrollment

4. Pregnancy or intent to become pregnant during the trial

5. Currently breastfeeding or planning to breastfeed

6. Currently being treated for a seizure disorder

7. Planned surgery during study duration

8. History of cardiac arrhythmia (except for benign premature atrial contractions and benign premature ventricular contractions which are permitted)

9. Clinically significant electrocardiogram (ECG) abnormality at time of Screening, as interpreted by the study medical physician

10. Use of diuretics (e.g. Lasix, Thiazides)

11. History of chronic or recurrent genital infections

12. eGFR lab value below 60 mL/min/1.73 m2

13. Treatment with any non-insulin glucose-lowering agent (including metformin, GLP-1 agonists, pramlintide, DPP-4 inhibitors, SGLT-2 inhibitors, biguanides, sulfonylureas and naturaceuticals)

14. A known medical condition that in the judgment of the investigator might interfere with the completion of the protocol such as the following examples:

1. Severe renal impairment, end-stage renal disease, or dialysis

2. Inpatient psychiatric treatment in the past six months

3. Presence of a known adrenal disorder

4. Abnormal liver function test results (Transaminase>2 times the upper limit of normal); testing required for subjects taking medications known to affect liver function or with diseases known to affect liver function

5. Uncontrolled thyroid disease

15. Severe renal impairment, end-stage renal disease, or dialysis

16. Use of an automated insulin delivery mechanism that is not downloadable by the subject or study team

17. Current enrollment in another clinical trial, unless approved by the investigator of both studies or if clinical trial is a non-interventional registry trial

18. Alcohol restricted to no more than 2 drinks per night in men and no more than 1 drink per night in women

19. Low carb diet (less than 100g per day)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

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

NIH

Sponsor Role: collaborator

Tandem Diabetes Care, Inc.

INDUSTRY

Sponsor Role: collaborator

DexCom, Inc.

INDUSTRY

Sponsor Role: collaborator

Ananda Basu, MD

OTHER

Sponsor Role: lead

Responsible Party

Ananda Basu, MD

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Ananda Basu, MD

Role: PRINCIPAL_INVESTIGATOR

University of Virginia

Ralf Nass, MD

Role: STUDY_CHAIR

University of Virginia

Locations

University of Virginia, Center for Diabetes Technology

Charlottesville, Virginia, United States

Countries

United States

References

Garcia-Tirado J, Farhy L, Nass R, Kollar L, Clancy-Oliveri M, Basu R, Kovatchev B, Basu A. Automated Insulin Delivery with SGLT2i Combination Therapy in Type 1 Diabetes. Diabetes Technol Ther. 2022 Jul;24(7):461-470. doi: 10.1089/dia.2021.0542. Epub 2022 Mar 14.

Reference Type: DERIVED

PMID: 35255229 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

DP3DK106785

Identifier Type: NIH

Identifier Source: secondary_id

View Link

190017

Identifier Type: -

Identifier Source: org_study_id