Triple Therapy in T1DM

Type 1 Diabetes Mellitus Clinical Trial

Official title:

Triple Therapy for Type 1 Diabetes With Insulin, Semaglutide, and Dapagliflozin

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03899402
• Other study ID #: STUDY00002775
• Secondary ID: 1987
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: May 1, 2019
• Est. completion date: March 1, 2025

Study information

• Verified date: December 2023
• Source: State University of New York at Buffalo
• Contact: Paresh Dandona, MD
• Phone: 716-535-1850
• Email: dandona[@]buffalo.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To assess whether the addition of dapagliflozin to semaglutide and insulin (triple therapy) improves glycemic control in patients with type 1 diabetes compared with semaglutide and insulin (dual therapy) and insulin only (standard) treatment.

Description:

This will be a 52 week study for type 1 diabetics looking into the effect of semaglutide and dapagliflozin on HbA1c and glycemic control.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 114
• Est. completion date: March 1, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Type 1 Diabetes for at least 1 year on staple use of continuous subcutaneous insulin infusion (CSII) or multiple daily (four or more) injections (MDI) of insulin for last 3 months.

2. C-peptide <0.23 nM

3. Minimum dose of insulin in Units/kg at entry: 0.5 U/kg for MDI and 0.4 U/kg for CSII

4. Regularly measuring blood sugars four or more times daily.

5. HbA1c of >7.5%.

6. Well versed in CHO counting*

7. Age 18-70 years.

8. BMI =25 kg/m2.

Exclusion Criteria:

1. Type 1 diabetes for less than 12 months, type 2 diabetes, chronic pancreatitis, MODY

2. Previous use of any agent other than insulin for treatment of diabetes in the last 3 months.

3. History of diabetic ketoacidosis (DKA) requiring medical intervention (e.g., emergency room visit and/or hospitalization) within 3 month prior to the screening visit

4. Frequent episodes of severe hypoglycemia as defined by more than one episode requiring medical assistance, emergency care (paramedics or emergency room care), and/or glucagon therapy administered by a third-party individual within 1 month prior to the screening visit

5. Symptoms of poorly controlled diabetes that would preclude participation in this trial

6. Subjects on a commercial weight loss program with ongoing weight loss, or on an intensive exercise program

7. History of bariatric surgery or lap-band procedure within 12 months prior to screening

8. History of Addison's disease or chronic adrenal insufficiency

9. History of diabetes insipidus

10. Hepatic disease or cirrhosis with Aspartate Aminotransferase (AST) > 3X Upper limit of normal (ULN) and/or Alanine aminotransferase (ALT) > 3X ULN

11. Serum Total Bilirubin > 2X ULN unless exclusively caused by Gilbert's Syndrome

12. Hemoglobin < 11.0 g/dL (110 g/L) for men; hemoglobin < 10.0 g/dL (100 g/L) for women.

13. Coronary event or procedure (myocardial infarction, unstable angina, coronary artery bypass, surgery or coronary angioplasty) in the previous 3 months or patients with congestive heart failure.

14. ESRD on hemodialysis; and or e-GFR < 60 ml/min/1.73m2

15. HIV or Hepatitis B/C positive status

16. Any other life-threatening, noncardiac disease

17. History of pancreatitis

18. Women who are pregnant or women of childbearing potential who are not using adequate contraception or who are breast feeding

19. Inability to give informed consent

20. History of gastroparesis

21. History of medullary thyroid carcinoma or MEN 2 syndrome

22. History of serious hypersensitivity reaction to these agents

23. Painful gallstones

24. Alcoholism

25. Hypertriglyceridemia (>500 mg/dl)

26. Recurrent genital mycotic infection.

27. Hypovolemic patients or with chronic renal insufficiency.

28. Patients with any malignancy except treated in situ malignancy and basal cell carcinoma of the skin

29. Unexplained hematuria

30. Patients with a history of diabetic retinopathy

31. Use of an investigational agent or therapeutic regimen within 30 days of study

32. Participation in any other concurrent interventional clinical trial

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 1
• Type 1 Diabetes Mellitus

Intervention

Drug:
• Insulin
Standard of care insulin for pump or injection and serves as a control
• Semaglutide
Injectable weekly GLP-1RA given as open label experimental drug
• Dapagliflozin
Oral daily SGLT2 Inhibitor given as experimental drug
• Placebo to Dapagliflozin
Placebo to Dapagliflozin given as a control to the experimental drug

Locations

Country	Name	City	State
United States	Diabetes and Endocrinology Research Center of WNY	Williamsville	New York

Sponsors (3)

Lead Sponsor	Collaborator
State University of New York at Buffalo	Juvenile Diabetes Research Foundation, University of Glasgow

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in HbA1c following dapagliflozin	Change in HbA1c at 6 months following dapagliflozin or placebo therapy in addition to combined semaglutide and insulin treatment.	6 months
Secondary	Change in HbA1c with triple therapy	Change in HbA1c from baseline at 12 months in triple therapy group compared to insulin only group.	12 months
Secondary	Change in HbA1c with semaglutide	Change in HbA1c from baseline at 6 months in dual therapy group (insulin and semaglutide) compared to insulin only group.	6 months
Secondary	Assessment of hyperglycemia level 1	Change in percent Time hyperglycemia Level 1(180-250mg/dl) as assessed by CGM	12 months
Secondary	Assessment of hyperglycemia level 2	Change in percent Time in hyperglycemia Level 2 ( >250mg/dl) as assessed by CGM	12 months
Secondary	Assessment of hypoglycemia	Change in percent Time in hypoglycemia Level 1 (54-70mg/dl) as assessed by CGM	12 months
Secondary	Assessment of percent time glucose in range	Change in percent Time in Range (70- 180 mg/dl) as assessed by CGM	12 months
Secondary	Fructosamine indices	Assessment of fructosamine	12 months
Secondary	Weekly fasting glucose indices	Assessment of change of weekly fasting glucose	12 months
Secondary	Insulin requirement indices	Assessment of the change in insulin requirement	12 months
Secondary	body weight assessment following dapagliflozin	Change in body weight at 6 months between dapagliflozin and placebo groups.	6 months
Secondary	body weight assessment following semaglutide	Change in body weight at 6 months following starting semaglutide compared to standard of care (SOC) group.	6 months
Secondary	body weight assessment following triple therapy	Change in body weight as assessed at 12 months on dapagliflozin and semaglutide compared to SOC therapy.	12 months
Secondary	Systolic Blood pressure assessment after triple therapy	Anti-hypertensive effects including change in systolic BP on dapagliflozin and semaglutide compared to SOC therapy.	12 months
Secondary	Diastolic Blood pressure assessment	Anti-hypertensive effects including change in diastolic BP on dapagliflozin and semaglutide compared to SOC therapy.	12 months
Secondary	Blood pressure medication use	Anti-hypertensive effects including change in numbers of BP medications required in patients dapagliflozin and semaglutide compared to SOC therapy.	12 months
Secondary	Level 2 hypoglycemia assessment	Differences in rates of hypoglycemic events Level 2 (<54mg/dl) between triple therapy and in standard therapy arm.	12 months
Secondary	Severe (level 3) hypoglycemia assessment	Differences in rates of hypoglycemic events Level 3 (<54mg/dl) characterized by altered mental and/or physical status requiring assistance) between triple therapy and in standard therapy arm.	12 months
Secondary	Level 1 hyperglycemia assessment	Differences in rates of Level 1 hyperglycemia (glucose levels >180mg/dl and <250mg dl) between triple therapy and in standard therapy arm.	12 months
Secondary	Level 2 hyperglycemia assessment	Differences in rates of Level 2 hyperglycemia (glucose levels <250mg dl) between triple therapy and in standard therapy arm.	12 months
Secondary	serum ketones assessment	Differences in rates of diabetic ketoacidosis defined as elevated serum ketones (greater than the upper limit of the normal range) in investigative arms.	12 months
Secondary	Urinary ketones assessment	Differences in rates of diabetic ketoacidosis defined as elevated urine ketones (greater than the upper limit of the normal range) in investigative arms.	12 months
Secondary	Diabetic ketoacidosis assessment	Differences in rates of diabetic ketoacidosis defined as Blood pH <7.3 in investigative arms.	12 months