NCT02962492

Brief Summary

The study investigations include evaluation of the acute effects of a single dose of dapagliflozin (10mg), exenatide (5µg), a combination of exenatide and dapagliflozin or placebo under insulinopenic condition and the long term effect under basal conditions before and after 12 weeks treatment with dapagliflozin, Exenatide extended release, a combination of Exenatide extended release and dapagliflozin or placebo on ketogenesis, glucagon and lipolysis.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
70

participants targeted

Target at P50-P75 for not_applicable

Timeline
Completed

Started Nov 2016

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 1, 2016

Completed
8 days until next milestone

First Submitted

Initial submission to the registry

November 9, 2016

Completed
2 days until next milestone

First Posted

Study publicly available on registry

November 11, 2016

Completed
4.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2021

Completed
9 months until next milestone

Study Completion

Last participant's last visit for all outcomes

October 24, 2021

Completed
2.4 years until next milestone

Results Posted

Study results publicly available

February 29, 2024

Completed
Last Updated

February 29, 2024

Status Verified

February 1, 2024

Enrollment Period

4.3 years

First QC Date

November 9, 2016

Results QC Date

November 21, 2022

Last Update Submit

February 3, 2024

Conditions

Evaluate Ketogenic Stress

Keywords

DapagliflozinKetogenesisType 1 DiabetesDKAketonesexenatide/Bydureon

Outcome Measures

Primary Outcomes (1)

  • Change in Beta-hydroxybutyrate Levels in Blood

    Beta-hydroxybutyrate (BHB) was measured in blood during the acute stress conditions in all the groups after single dose intervention at baseline (0 Week) and at 12 weeks of treatment. The magnitude of change at each of these visits was calculated from each visit baseline (0 hr) and the difference between the change at 12 weeks was compared to the change at 0 week and reported as: Change at week 12 - change at week 0.

    12 weeks

Secondary Outcomes (4)

  • Change in HbA1c Following Treatment

    12 weeks

  • Change in Urinary Beta-hydroxybutyrate (BHB) After 12 Weeks of Treatment

    12 weeks

  • Change in Plasma Glucagon

    12 weeks

  • Change in Total Insulin Dose

    12 weeks

Study Arms (4)

Dapagliflozin Arm:

ACTIVE COMPARATOR

dapagliflozin 10mg (oral tablet) and exenatide (5µg acutely)/Exenatide extended release (long term) placebo (subcutaneous injection)

Drug: Dapagliflozin

Exenatide extended release Arm:

ACTIVE COMPARATOR

subcutaneous injection of Exenatide (5µg acutely)/Exenatide extended release (long term) and dapagliflozin placebo

Drug: Exenatide/Exenatide extended release

Placebo Arm:

PLACEBO COMPARATOR

dapagliflozin placebo (oral tablet) and exenatide (5µg acutely)/Exenatide extended release (long term) placebo (subcutaneous injection)

Drug: Placebo

Exenatide extended release & dapagliflozin Arm:

ACTIVE COMPARATOR

Exenatide (5µg acutely)/Exenatide extended release (long term) and dapagliflozin 10mg

Drug: Exenatide/Exenatide extended releaseDrug: Dapagliflozin

Interventions

Exenatide/Exenatide extended releaseDRUG

Eighty (80) patients with T1D will be enrolled and randomized into 4 groups(20 each) to receive placebo, or dapagliflozin, or exenatide (5µg acutely)/Exenatide extended release (long term), or exenatide (5µg acutely)/Exenatide extended release (long term) and dapagliflozin treatments acutely and for 12 weeks

Also known as: Bydureon
Exenatide extended release & dapagliflozin Arm:Exenatide extended release Arm:
DapagliflozinDRUG

Eighty (80) patients with T1D will be enrolled and randomized into 4 groups(20 each) to receive placebo, or dapagliflozin, or exenatide (5µg acutely)/Exenatide extended release (long term), or exenatide (5µg acutely)/Exenatide extended release (long term) and dapagliflozin treatments acutely and for 12 weeks

Also known as: Farxiga
Dapagliflozin Arm:Exenatide extended release & dapagliflozin Arm:
PlaceboDRUG

Eighty (80) patients with T1D will be enrolled and randomized into 4 groups(20 each) to receive placebo, or dapagliflozin, or exenatide (5µg acutely)/Exenatide extended release (long term), or exenatide (5µg acutely)/Exenatide extended release (long term) and dapagliflozin treatments acutely and for 12 weeks

Also known as: Placebo for both active drugs
Placebo Arm:

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Type 1 Diabetes for at least 1 year on continuous subcutaneous insulin infusion (CSII; also known as insulin pump)
  • HbA1c of 7-10% (inclusive)
  • Ages 18-65 years (inclusive of ages 18 and 65)
  • BMI 20-30 kg/m2

You may not qualify if:

  • Inability to give informed consent
  • Inability or refusal to comply with protocol
  • Use of GLP-1 Receptor Agonists in the last 3 months or DPP-IV and SGLT-2 inhibitors therapy in the last 1 month.
  • Risk for pancreatitis (e.g., history of gallstones, alcohol abuse, and hypertriglyceridemia)
  • History of pancreatitis and or chronic pancreatitis
  • Coronary event or procedure (myocardial infarction, unstable angina, coronary artery bypass, surgery or coronary angioplasty) or stroke in the previous 3 months.
  • Congestive Heart Failure class III or IV or tachyarrhythmia.
  • Hepatic disease: Severe hepatic insufficiency and/or significant abnormal liver function defined as:
  • Aspartate aminotransferase (AST) \>3x upper limit of normal (ULN) and/or alanine aminotransferase (ALT) \>3x ULN
  • Total bilirubin \>2.0 mg/dL (34.2 µmol/L)
  • Positive serologic evidence of current infectious liver disease including Hepatitis B viral antibody IGM, Hepatitis B surface antigen and Hepatitis C virus antibody
  • Liver function tests more than 3 times the upper limit of normal
  • Renal impairment (e.g., serum creatinine levels ≥1.4 mg/dL for women, or eGFR \<60 mL/min/1.73 m2) or history of unstable or rapidly progressing renal disease or end stage renal disease.
  • History of unexplained microscopic or gross hematuria, or microscopic hematuria at visit 1, confirmed by a follow-up sample at next scheduled visit.
  • HIV positive
  • +20 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Diabetes and Endocrinology Research Center of WNY

Williamsville, New York, 14221, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1Ketosis

Interventions

Exenatidedapagliflozin

Condition Hierarchy (Ancestors)

Diabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System DiseasesAutoimmune DiseasesImmune System DiseasesAcidosisAcid-Base Imbalance

Intervention Hierarchy (Ancestors)

PeptidesAmino Acids, Peptides, and ProteinsVenomsComplex MixturesToxins, BiologicalBiological Factors

Results Point of Contact

Title
Dr. Paresh Dandona
Organization
State University of NY at Buffalo
dandona@buffalo.edu
7165351850

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
SUNY Distinguished Professor

Study Record Dates

First Submitted

November 9, 2016

First Posted

November 11, 2016

Study Start

November 1, 2016

Primary Completion

February 1, 2021

Study Completion

October 24, 2021

Last Updated

February 29, 2024

Results First Posted

February 29, 2024

Record last verified: 2024-02

Data Sharing

IPD Sharing
Will not share

Locations

US(1)