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Triple Therapy in T1DM

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ClinicalTrials.gov Identifier: NCT03899402
Recruitment Status : Recruiting
First Posted : April 2, 2019
Last Update Posted : October 2, 2019
Sponsor:
Collaborator:
University of Glasgow
Information provided by (Responsible Party):
Paresh Dandona, State University of New York at Buffalo

Tracking Information
First Submitted Date  ICMJE March 26, 2019
First Posted Date  ICMJE April 2, 2019
Last Update Posted Date October 2, 2019
Actual Study Start Date  ICMJE May 1, 2019
Estimated Primary Completion Date May 1, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 29, 2019)
Change in HbA1c [ Time Frame: 6 months ]
Change in HbA1c at 6 months following dapagliflozin or placebo therapy in addition to combined semaglutide and insulin treatment.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03899402 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 29, 2019)
  • Change in HbA1c [ Time Frame: 12 months ]
    Change in HbA1c from baseline at 12 months in triple therapy group compared to insulin only group.
  • Change in HbA1c [ Time Frame: 6 months ]
    Change in HbA1c from baseline at 6 months in dual therapy group compared to insulin only group.
  • Assessment of hyperglycemia level 1 [ Time Frame: 12 months ]
    Change in percent Time hyperglycemia Level 1(180-250mg/dl) as assessed by CGM
  • Assessment of hyperglycemia level 2 [ Time Frame: 12 months ]
    Change in percent Time in hyperglycemia Level 2 ( >250mg/dl) as assessed by CGM
  • Assessment of hypoglycemia [ Time Frame: 12 months ]
    Change in percent Time in hypoglycemia Level 1 (54-70mg/dl) as assessed by CGM
  • Assessment of percent time glucose in range [ Time Frame: 12 months ]
    Change in percent Time in Range (70- 180 mg/dl) as assessed by CGM
  • Fructosamine indices [ Time Frame: 12 months ]
    Assessment of fructosamine
  • Weekly fasting glucose indices [ Time Frame: 12 months ]
    Assessment of change of weekly fasting glucose
  • Insulin requirement indices [ Time Frame: 12 months ]
    Assessment of the change in insulin requirement
  • body weight assessment [ Time Frame: 6 months ]
    Change in body weight as assessed by DSQOLS questionnaire at 6 months.
  • body weight assessment [ Time Frame: 6 months ]
    Change in quality of life as assessed by DSQOLS questionnaire at 6 months.
  • body weight assessment [ Time Frame: 12 months ]
    Change in body weight as assessed by DSQOLS questionnaire at 12 months.
  • body weight assessment [ Time Frame: 12 months ]
    Change in quality of life as assessed by DSQOLS questionnaire at 12 months.
  • body weight assessment [ Time Frame: 6 months ]
    Change in body weight as assessed by PAID questionnaire at 6 months.
  • body weight assessment [ Time Frame: 6 months ]
    Change in quality of life as assessed by PAID questionnaire at 6 months.
  • body weight assessment [ Time Frame: 12 months ]
    Change in body weight as assessed by PAID questionnaire at 12 months.
  • body weight assessment [ Time Frame: 12 months ]
    Change in quality of life as assessed by PAID questionnaire at 12 months.
  • Blood pressure assessment [ Time Frame: 12 months ]
    Anti-hypertensive effects including change in systolic BP.
  • Blood pressure assessment [ Time Frame: 12 months ]
    Anti-hypertensive effects including change in diastolic BP
  • Blood pressure assessment [ Time Frame: 12 months ]
    Anti-hypertensive effects including change in numbers of BP medications required.
  • Severe hypoglycemia assessment [ Time Frame: 12 months ]
    Differences in rates of hypoglycemic events Level 2 (<54mg/dl) characterized by altered mental and/or physical status requiring assistance) in standard therapy arm.
  • Severe hypoglycemia assessment [ Time Frame: 12 months ]
    Differences in rates of hypoglycemic events Level 2 (<54mg/dl) characterized by altered mental and/or physical status requiring assistance) in investigative arms.
  • Severe hyperglycemia assessment [ Time Frame: 12 months ]
    Differences in rates of Level 3 hyperglycemia (A severe event characterized by altered mental and/or physical status requiring assistance) between in investigative arms.
  • Severe hyperglycemia assessment [ Time Frame: 12 months ]
    Differences in rates of Level 3 hyperglycemia (A severe event characterized by altered mental and/or physical status requiring assistance) in standard therapy arm.
  • Diabetic ketoacidosis assessment [ Time Frame: 12 months ]
    Differences in rates of diabetic ketoacidosis defined as elevated serum ketones (greater than the upper limit of the normal range) in investigative arms.
  • Diabetic ketoacidosis assessment [ Time Frame: 12 months ]
    Differences in rates of diabetic ketoacidosis defined as elevated urine ketones (greater than the upper limit of the normal range) in investigative arms.
  • Diabetic ketoacidosis assessment [ Time Frame: 12 months ]
    Differences in rates of diabetic ketoacidosis defined as elevated serum bicarbonate <15 mmol/L in investigative arms.
  • Diabetic ketoacidosis assessment [ Time Frame: 12 months ]
    Differences in rates of diabetic ketoacidosis defined as Blood pH <7.3 in investigative arms.
  • Diabetic ketoacidosis assessment [ Time Frame: 12 months ]
    Differences in rates of diabetic ketoacidosis defined as elevated serum ketones (greater than the upper limit of the normal range) in standard therapy arm.
  • Diabetic ketoacidosis assessment [ Time Frame: 12 months ]
    Differences in rates of diabetic ketoacidosis defined as elevated urine ketones (greater than the upper limit of the normal range) in standard therapy arm.
  • Diabetic ketoacidosis assessment [ Time Frame: 12 months ]
    Differences in rates of diabetic ketoacidosis defined as elevated serum bicarbonate <15 mmol/L in standard therapy arm.
  • Diabetic ketoacidosis assessment [ Time Frame: 12 months ]
    Differences in rates of diabetic ketoacidosis defined as elevated Blood pH <7.3 in standard therapy arm.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Triple Therapy in T1DM
Official Title  ICMJE Triple Therapy for Type 1 Diabetes With Insulin, Semaglutide, and Dapagliflozin
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
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.
Masking: Double (Participant, Investigator)
Masking 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
Condition  ICMJE Type 1 Diabetes Mellitus
Intervention  ICMJE
  • Drug: Insulin
    Standard of care insulin for pump or injection and serves as a control
  • Drug: Semaglutide
    Injectable weekly GLP-1RA given as open label experimental drug
    Other Name: Ozempic
  • Drug: Dapagliflozin
    Oral daily SGLT2 Inhibitor given as experimental drug
    Other Name: Farxigo
  • Drug: Placebo to Dapagliflozin
    Placebo to Dapagliflozin given as a control to the experimental drug
Study Arms  ICMJE
  • Active Comparator: Control
    Standard of care insulin will be used as an active comparator arm for 1/3 of patients (38 patients) for the entire duration of the study.
    Intervention: Drug: Insulin
  • Experimental: Dual Therapy
    Once a week injection of Semaglutide (a GLP-1 receptor agonist) in addition to standard of care insulin for the first six months in 2/3 of patients (76 patients). Semaglutide is a clear, colorless solution that contains 2 mg of semaglutide in a 1.5 mL (1.34 mg/mL) pre-filled, disposable, single-patient-use pen injector. Semaglutide will be started at the 0.25 mg dose for the first two weeks, then increased to 0.5 mg at week 2, and then yet again increased to 1.0 mg at week 4.
    Interventions:
    • Drug: Insulin
    • Drug: Semaglutide
  • Experimental: Triple therapy
    Once a day oral pill (green, plain, diamond shaped film coated 5 mg tablet) of Dapagliflozin (an SGLT-2 inhibitor) added to once a week injection of semaglutide and standard of care insulin in the second 6 months of 1/2 of the dual therapy arm (1/3 of total patients (38 patients)). Dapagliflozin will be started at 5 mg for one week, and then increased to 10 mg for the remainder of the study
    Interventions:
    • Drug: Insulin
    • Drug: Semaglutide
    • Drug: Dapagliflozin
  • Placebo Comparator: Triple therapy control
    Once a day oral pill (green, plain, diamond shaped film coated 5 mg tablet) of the Placebo form of Dapagliflozin added to once a week injection of semaglutide and standard of care insulin in the second 6 months of 1/2 of the dual therapy arm (1/3 of total patients (38 patients)).
    Interventions:
    • Drug: Insulin
    • Drug: Semaglutide
    • Drug: Placebo to Dapagliflozin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 29, 2019)
114
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 1, 2022
Estimated Primary Completion Date May 1, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Paresh Dandona, MD 716-535-1850 dandona@buffalo.edu
Contact: Husam Ghanim, PhD 716-881-8924 ghanim@buffalo.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03899402
Other Study ID Numbers  ICMJE STUDY00002775
1987 ( Other Identifier: Diabetes and Endocrinology Research Foundation )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Paresh Dandona, State University of New York at Buffalo
Study Sponsor  ICMJE State University of New York at Buffalo
Collaborators  ICMJE University of Glasgow
Investigators  ICMJE Not Provided
PRS Account State University of New York at Buffalo
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP