Back to resultsTriple Therapy in T1DM
Primary Purpose
Type 1 Diabetes Mellitus
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Insulin
Semaglutide
Dapagliflozin
Placebo to Dapagliflozin
Sponsored by
About this trial
This is an interventional treatment trial for Type 1 Diabetes Mellitus
Eligibility Criteria
Inclusion Criteria:
- 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.
- C-peptide <0.23 nM
- Minimum dose of insulin in Units/kg at entry: 0.5 U/kg for MDI and 0.4 U/kg for CSII
- Regularly measuring blood sugars four or more times daily.
- HbA1c of >7.5%.
- Well versed in CHO counting*
- Age 18-70 years.
- BMI ≥25 kg/m2.
Exclusion Criteria:
- Type 1 diabetes for less than 12 months, type 2 diabetes, chronic pancreatitis, MODY
- Previous use of any agent other than insulin for treatment of diabetes in the last 3 months.
- History of diabetic ketoacidosis (DKA) requiring medical intervention (e.g., emergency room visit and/or hospitalization) within 3 month prior to the screening visit
- 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
- Symptoms of poorly controlled diabetes that would preclude participation in this trial
- Subjects on a commercial weight loss program with ongoing weight loss, or on an intensive exercise program
- History of bariatric surgery or lap-band procedure within 12 months prior to screening
- History of Addison's disease or chronic adrenal insufficiency
- History of diabetes insipidus
- Hepatic disease or cirrhosis with Aspartate Aminotransferase (AST) > 3X Upper limit of normal (ULN) and/or Alanine aminotransferase (ALT) > 3X ULN
- Serum Total Bilirubin > 2X ULN unless exclusively caused by Gilbert's Syndrome
- Hemoglobin < 11.0 g/dL (110 g/L) for men; hemoglobin < 10.0 g/dL (100 g/L) for women.
- 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.
- ESRD on hemodialysis; and or e-GFR < 60 ml/min/1.73m2
- HIV or Hepatitis B/C positive status
- Any other life-threatening, noncardiac disease
- History of pancreatitis
- Women who are pregnant or women of childbearing potential who are not using adequate contraception or who are breast feeding
- Inability to give informed consent
- History of gastroparesis
- History of medullary thyroid carcinoma or MEN 2 syndrome
- History of serious hypersensitivity reaction to these agents
- Painful gallstones
- Alcoholism
- Hypertriglyceridemia (>500 mg/dl)
- Recurrent genital mycotic infection.
- Hypovolemic patients or with chronic renal insufficiency.
- Patients with any malignancy except treated in situ malignancy and basal cell carcinoma of the skin
- Unexplained hematuria
- Patients with a history of diabetic retinopathy
- Use of an investigational agent or therapeutic regimen within 30 days of study
- Participation in any other concurrent interventional clinical trial
Sites / Locations
- Diabetes and Endocrinology Research Center of WNYRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Active Comparator
Experimental
Experimental
Placebo Comparator
Arm Label
Control
Dual Therapy
Triple therapy
Triple therapy control
Arm Description
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.
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.
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
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)).
Outcomes
Primary Outcome Measures
Change in HbA1c
Change in HbA1c at 6 months following dapagliflozin or placebo therapy in addition to combined semaglutide and insulin treatment.
Secondary Outcome Measures
Change in HbA1c
Change in HbA1c from baseline at 12 months in triple therapy group compared to insulin only group.
Change in HbA1c
Change in HbA1c from baseline at 6 months in dual therapy group compared to insulin only group.
Assessment of hyperglycemia level 1
Change in percent Time hyperglycemia Level 1(180-250mg/dl) as assessed by CGM
Assessment of hyperglycemia level 2
Change in percent Time in hyperglycemia Level 2 ( >250mg/dl) as assessed by CGM
Assessment of hypoglycemia
Change in percent Time in hypoglycemia Level 1 (54-70mg/dl) as assessed by CGM
Assessment of percent time glucose in range
Change in percent Time in Range (70- 180 mg/dl) as assessed by CGM
Fructosamine indices
Assessment of fructosamine
Weekly fasting glucose indices
Assessment of change of weekly fasting glucose
Insulin requirement indices
Assessment of the change in insulin requirement
body weight assessment
Change in body weight as assessed by DSQOLS questionnaire at 6 months.
body weight assessment
Change in quality of life as assessed by DSQOLS questionnaire at 6 months.
body weight assessment
Change in body weight as assessed by DSQOLS questionnaire at 12 months.
body weight assessment
Change in quality of life as assessed by DSQOLS questionnaire at 12 months.
body weight assessment
Change in body weight as assessed by PAID questionnaire at 6 months.
body weight assessment
Change in quality of life as assessed by PAID questionnaire at 6 months.
body weight assessment
Change in body weight as assessed by PAID questionnaire at 12 months.
body weight assessment
Change in quality of life as assessed by PAID questionnaire at 12 months.
Blood pressure assessment
Anti-hypertensive effects including change in systolic BP.
Blood pressure assessment
Anti-hypertensive effects including change in diastolic BP
Blood pressure assessment
Anti-hypertensive effects including change in numbers of BP medications required.
Severe hypoglycemia assessment
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
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
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
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
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
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
Differences in rates of diabetic ketoacidosis defined as elevated serum bicarbonate <15 mmol/L in investigative arms.
Diabetic ketoacidosis assessment
Differences in rates of diabetic ketoacidosis defined as Blood pH <7.3 in investigative arms.
Diabetic ketoacidosis assessment
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
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
Differences in rates of diabetic ketoacidosis defined as elevated serum bicarbonate <15 mmol/L in standard therapy arm.
Diabetic ketoacidosis assessment
Differences in rates of diabetic ketoacidosis defined as elevated Blood pH <7.3 in standard therapy arm.
Full Information
NCT ID
NCT03899402
First Posted
March 26, 2019
Last Updated
September 10, 2022
Sponsor
State University of New York at Buffalo
Collaborators
University of Glasgow, Juvenile Diabetes Research Foundation
1. Study Identification
Unique Protocol Identification Number
NCT03899402
Brief Title
Triple Therapy in T1DM
Official Title
Triple Therapy for Type 1 Diabetes With Insulin, Semaglutide, and Dapagliflozin
Study Type
Interventional
2. Study Status
Record Verification Date
September 2022
Overall Recruitment Status
Recruiting
Study Start Date
May 1, 2019 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
March 1, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
State University of New York at Buffalo
Collaborators
University of Glasgow, Juvenile Diabetes Research Foundation
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 1 Diabetes Mellitus
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
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
ParticipantInvestigator
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.
Allocation
Randomized
Enrollment
114 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Control
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Dual Therapy
Arm Type
Experimental
Arm Description
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.
Arm Title
Triple therapy
Arm Type
Experimental
Arm Description
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
Arm Title
Triple therapy control
Arm Type
Placebo Comparator
Arm Description
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)).
Intervention Type
Drug
Intervention Name(s)
Insulin
Intervention Description
Standard of care insulin for pump or injection and serves as a control
Intervention Type
Drug
Intervention Name(s)
Semaglutide
Other Intervention Name(s)
Ozempic
Intervention Description
Injectable weekly GLP-1RA given as open label experimental drug
Intervention Type
Drug
Intervention Name(s)
Dapagliflozin
Other Intervention Name(s)
Farxigo
Intervention Description
Oral daily SGLT2 Inhibitor given as experimental drug
Intervention Type
Drug
Intervention Name(s)
Placebo to Dapagliflozin
Intervention Description
Placebo to Dapagliflozin given as a control to the experimental drug
Primary Outcome Measure Information:
Title
Change in HbA1c
Description
Change in HbA1c at 6 months following dapagliflozin or placebo therapy in addition to combined semaglutide and insulin treatment.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Change in HbA1c
Description
Change in HbA1c from baseline at 12 months in triple therapy group compared to insulin only group.
Time Frame
12 months
Title
Change in HbA1c
Description
Change in HbA1c from baseline at 6 months in dual therapy group compared to insulin only group.
Time Frame
6 months
Title
Assessment of hyperglycemia level 1
Description
Change in percent Time hyperglycemia Level 1(180-250mg/dl) as assessed by CGM
Time Frame
12 months
Title
Assessment of hyperglycemia level 2
Description
Change in percent Time in hyperglycemia Level 2 ( >250mg/dl) as assessed by CGM
Time Frame
12 months
Title
Assessment of hypoglycemia
Description
Change in percent Time in hypoglycemia Level 1 (54-70mg/dl) as assessed by CGM
Time Frame
12 months
Title
Assessment of percent time glucose in range
Description
Change in percent Time in Range (70- 180 mg/dl) as assessed by CGM
Time Frame
12 months
Title
Fructosamine indices
Description
Assessment of fructosamine
Time Frame
12 months
Title
Weekly fasting glucose indices
Description
Assessment of change of weekly fasting glucose
Time Frame
12 months
Title
Insulin requirement indices
Description
Assessment of the change in insulin requirement
Time Frame
12 months
Title
body weight assessment
Description
Change in body weight as assessed by DSQOLS questionnaire at 6 months.
Time Frame
6 months
Title
body weight assessment
Description
Change in quality of life as assessed by DSQOLS questionnaire at 6 months.
Time Frame
6 months
Title
body weight assessment
Description
Change in body weight as assessed by DSQOLS questionnaire at 12 months.
Time Frame
12 months
Title
body weight assessment
Description
Change in quality of life as assessed by DSQOLS questionnaire at 12 months.
Time Frame
12 months
Title
body weight assessment
Description
Change in body weight as assessed by PAID questionnaire at 6 months.
Time Frame
6 months
Title
body weight assessment
Description
Change in quality of life as assessed by PAID questionnaire at 6 months.
Time Frame
6 months
Title
body weight assessment
Description
Change in body weight as assessed by PAID questionnaire at 12 months.
Time Frame
12 months
Title
body weight assessment
Description
Change in quality of life as assessed by PAID questionnaire at 12 months.
Time Frame
12 months
Title
Blood pressure assessment
Description
Anti-hypertensive effects including change in systolic BP.
Time Frame
12 months
Title
Blood pressure assessment
Description
Anti-hypertensive effects including change in diastolic BP
Time Frame
12 months
Title
Blood pressure assessment
Description
Anti-hypertensive effects including change in numbers of BP medications required.
Time Frame
12 months
Title
Severe hypoglycemia assessment
Description
Differences in rates of hypoglycemic events Level 2 (<54mg/dl) characterized by altered mental and/or physical status requiring assistance) in standard therapy arm.
Time Frame
12 months
Title
Severe hypoglycemia assessment
Description
Differences in rates of hypoglycemic events Level 2 (<54mg/dl) characterized by altered mental and/or physical status requiring assistance) in investigative arms.
Time Frame
12 months
Title
Severe hyperglycemia assessment
Description
Differences in rates of Level 3 hyperglycemia (A severe event characterized by altered mental and/or physical status requiring assistance) between in investigative arms.
Time Frame
12 months
Title
Severe hyperglycemia assessment
Description
Differences in rates of Level 3 hyperglycemia (A severe event characterized by altered mental and/or physical status requiring assistance) in standard therapy arm.
Time Frame
12 months
Title
Diabetic ketoacidosis assessment
Description
Differences in rates of diabetic ketoacidosis defined as elevated serum ketones (greater than the upper limit of the normal range) in investigative arms.
Time Frame
12 months
Title
Diabetic ketoacidosis assessment
Description
Differences in rates of diabetic ketoacidosis defined as elevated urine ketones (greater than the upper limit of the normal range) in investigative arms.
Time Frame
12 months
Title
Diabetic ketoacidosis assessment
Description
Differences in rates of diabetic ketoacidosis defined as elevated serum bicarbonate <15 mmol/L in investigative arms.
Time Frame
12 months
Title
Diabetic ketoacidosis assessment
Description
Differences in rates of diabetic ketoacidosis defined as Blood pH <7.3 in investigative arms.
Time Frame
12 months
Title
Diabetic ketoacidosis assessment
Description
Differences in rates of diabetic ketoacidosis defined as elevated serum ketones (greater than the upper limit of the normal range) in standard therapy arm.
Time Frame
12 months
Title
Diabetic ketoacidosis assessment
Description
Differences in rates of diabetic ketoacidosis defined as elevated urine ketones (greater than the upper limit of the normal range) in standard therapy arm.
Time Frame
12 months
Title
Diabetic ketoacidosis assessment
Description
Differences in rates of diabetic ketoacidosis defined as elevated serum bicarbonate <15 mmol/L in standard therapy arm.
Time Frame
12 months
Title
Diabetic ketoacidosis assessment
Description
Differences in rates of diabetic ketoacidosis defined as elevated Blood pH <7.3 in standard therapy arm.
Time Frame
12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
C-peptide <0.23 nM
Minimum dose of insulin in Units/kg at entry: 0.5 U/kg for MDI and 0.4 U/kg for CSII
Regularly measuring blood sugars four or more times daily.
HbA1c of >7.5%.
Well versed in CHO counting*
Age 18-70 years.
BMI ≥25 kg/m2.
Exclusion Criteria:
Type 1 diabetes for less than 12 months, type 2 diabetes, chronic pancreatitis, MODY
Previous use of any agent other than insulin for treatment of diabetes in the last 3 months.
History of diabetic ketoacidosis (DKA) requiring medical intervention (e.g., emergency room visit and/or hospitalization) within 3 month prior to the screening visit
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
Symptoms of poorly controlled diabetes that would preclude participation in this trial
Subjects on a commercial weight loss program with ongoing weight loss, or on an intensive exercise program
History of bariatric surgery or lap-band procedure within 12 months prior to screening
History of Addison's disease or chronic adrenal insufficiency
History of diabetes insipidus
Hepatic disease or cirrhosis with Aspartate Aminotransferase (AST) > 3X Upper limit of normal (ULN) and/or Alanine aminotransferase (ALT) > 3X ULN
Serum Total Bilirubin > 2X ULN unless exclusively caused by Gilbert's Syndrome
Hemoglobin < 11.0 g/dL (110 g/L) for men; hemoglobin < 10.0 g/dL (100 g/L) for women.
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.
ESRD on hemodialysis; and or e-GFR < 60 ml/min/1.73m2
HIV or Hepatitis B/C positive status
Any other life-threatening, noncardiac disease
History of pancreatitis
Women who are pregnant or women of childbearing potential who are not using adequate contraception or who are breast feeding
Inability to give informed consent
History of gastroparesis
History of medullary thyroid carcinoma or MEN 2 syndrome
History of serious hypersensitivity reaction to these agents
Painful gallstones
Alcoholism
Hypertriglyceridemia (>500 mg/dl)
Recurrent genital mycotic infection.
Hypovolemic patients or with chronic renal insufficiency.
Patients with any malignancy except treated in situ malignancy and basal cell carcinoma of the skin
Unexplained hematuria
Patients with a history of diabetic retinopathy
Use of an investigational agent or therapeutic regimen within 30 days of study
Participation in any other concurrent interventional clinical trial
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Paresh Dandona, MD
Phone
716-535-1850
Email
dandona@buffalo.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Husam Ghanim, PhD
Phone
716-881-8924
Email
ghanim@buffalo.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Husam Ghanim, PhD
Organizational Affiliation
State University of NY at Buffalo
Official's Role
Study Director
Facility Information:
Facility Name
Diabetes and Endocrinology Research Center of WNY
City
Williamsville
State/Province
New York
ZIP/Postal Code
14221
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jeanne Hejna, LPN
Phone
716-535-1850
Email
jeannehe@buffalo.edu
First Name & Middle Initial & Last Name & Degree
Husam A Ghanim, PhD
Phone
716-535-1852
Email
ghanim@buffalo.edu
12. IPD Sharing Statement
Plan to Share IPD
No
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Triple Therapy in T1DM
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