Clinical trial NCT03899402: Triple Therapy in T1DM
Official title: Triple Therapy for Type 1 Diabetes With Insulin, Semaglutide, and Dapagliflozin
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Type 1 Diabetes Mellitus
Lead sponsor: State University of New York at Buffalo
Sponsor class: OTHER
Collaborators: name: University of Glasgow
name: Juvenile Diabetes Research Foundation
First posted: 2019-04-02
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This will be a two-center, randomized, open-label then double-blind, parallel group, placebo and standard of care controlled prospective study in type 1 diabetes.
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in HbA1c following dapagliflozin
timeFrame: 6 months
Secondary outcomes:
measure: Change in HbA1c with triple therapy
timeFrame: 12 months
measure: Change in HbA1c with semaglutide
timeFrame: 6 months
measure: Assessment of hyperglycemia level 1
timeFrame: 12 months
measure: Assessment of hyperglycemia level 2
timeFrame: 12 months
measure: Assessment of hypoglycemia
timeFrame: 12 months
measure: Assessment of percent time glucose in range
timeFrame: 12 months
measure: Fructosamine indices
timeFrame: 12 months
measure: Weekly fasting glucose indices
timeFrame: 12 months
measure: Insulin requirement indices
timeFrame: 12 months
measure: body weight assessment following dapagliflozin
timeFrame: 6 months
measure: body weight assessment following semaglutide
timeFrame: 6 months
measure: body weight assessment following triple therapy
timeFrame: 12 months
measure: Systolic Blood pressure assessment after triple therapy
timeFrame: 12 months
measure: Diastolic Blood pressure assessment
timeFrame: 12 months
measure: Blood pressure medication use
timeFrame: 12 months
measure: Level 2 hypoglycemia assessment
timeFrame: 12 months
measure: Severe (level 3) hypoglycemia assessment
timeFrame: 12 months
measure: Level 1 hyperglycemia assessment
timeFrame: 12 months
measure: Level 2 hyperglycemia assessment
timeFrame: 12 months
measure: serum ketones assessment
timeFrame: 12 months
measure: Urinary ketones assessment
timeFrame: 12 months
measure: Diabetic ketoacidosis assessment
timeFrame: 12 months
Other outcomes:
Locations:
city: Williamsville
country: United States
facility: Diabetes and Endocrinology Research Center of WNY
state: New York
Study officials:
affiliation: State University of NY at Buffalo
name: Husam Ghanim, PhD
role: STUDY_DIRECTOR
References: