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Trial · Interventional

CompletedNot applicableResults postedRegistry data

An Investigation Into the Effect of Dapagliflozin on Ketogenesis in Type 1 Diabetes

Overview

Status
Completed
Phase
Not applicable
Enrollment
70 participants (actual)
Sponsor
University at Buffalo · Other
Design
Randomized · Triple masking
Countries
1 country

United States

Start
1 Nov 2016
Primary completion
1 Feb 2021
Completion
24 Oct 2021
First posted
11 Nov 2016 (estimated)
Last update posted
29 Feb 2024
Conditions
Evaluate Ketogenic Stress

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2016201720182019202020212022
  1. N/A

    An Investigation Into the Effect of Dapagliflozin on Ketogenesis in Type 1 Diabetes

    NCT02962492

    1 Nov 2016 to 24 Oct 2021

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

  • Exenatide/Exenatide extended releaseDrug
  • DapagliflozinDrug
  • PlaceboDrug

Arms4

  • Active comparator

    Dapagliflozin Arm:

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

  • Active comparator

    Exenatide extended release Arm:

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

  • Placebo comparator

    Placebo Arm:

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

  • Active comparator

    Exenatide extended release & dapagliflozin Arm:

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

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Change in Beta-hydroxybutyrate Levels in Blood

    Time frame · 12 weeks

    Registry description

    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.

Secondary outcomes(4)
  1. Change in HbA1c Following Treatment

    Time frame · 12 weeks

    Registry description

    Hemoglobin A1c (HbA1c) was measured in basal conditions in all the groups at week 0 and week 12 of treatment. The change in HbA1c from baseline at 12 weeks is calculated as: HbA1c at week 12 - HbA1c at week 0.

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

    Time frame · 12 weeks

    Registry description

    Beta-hydroxybutyrate (BHB) was measured in urine 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.

  3. Change in Plasma Glucagon

    Time frame · 12 weeks

    Registry description

    change in basal plasma glucagon after 12 weeks of dapagliflozin and Bydureon or combination of both treatments compared to baseline

  4. Change in Total Insulin Dose

    Time frame · 12 weeks

    Registry description

    change in total (basal or long acting and short acting) insulin daily dose calculated as daily units/Kg body weight at 12 weeks from baseline (0 week). Long acting or basal insulin dose (in units of insulin) plus short acting (meal) insulin doses administered through the day and reported by patients in patients logs or from insulin pumps are added and divided by body weight in Kg. The reported total insulin dose/Kg represents the average of last 3-7 days before the visit.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeMean· 12 weeks

Change in Beta-hydroxybutyrate Levels in Blood

GroupValue (mM)Spread
Placebo Arm:-0.230.17
Dapagliflozin Arm:0.630.22
Exenatide Extended Release Arm:0.240.21
Exenatide Extended Release & Dapagliflozin Arm:0.310.19
Secondary and other outcome results(4)
Secondary outcomeMean· 12 weeks

Change in HbA1c Following Treatment

GroupValue (Percent of Hemoglobin (%))Spread
Dapagliflozin Arm:-0.30.1
Exenatide Extended Release Arm:-0.40.2
Placebo Arm:-0.10.1
Exenatide Extended Release & Dapagliflozin Arm:-0.90.1
Secondary outcomeMean· 12 weeks

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

GroupValue (mM)Spread
Placebo Arm:1.20.5
Dapagliflozin Arm:0.40.2
Exenatide Extended Release Arm:-0.70.6
Exenatide Extended Release & Dapagliflozin Arm:1.10.4
Secondary outcomeMean· 12 weeks

Change in Plasma Glucagon

GroupValue (pg/ml)Spread
Placebo Arm:22
Dapagliflozin Arm:1610
Exenatide Extended Release Arm:-158
Exenatide Extended Release & Dapagliflozin Arm:-106
Secondary outcomeMean· 12 weeks

Change in Total Insulin Dose

GroupValue (Units/Kg)Spread
Placebo Arm:-0.010.02
Dapagliflozin Arm:-0.020.02
Exenatide Extended Release Arm:-0.050.02
Exenatide Extended Release & Dapagliflozin Arm:-0.040.02

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Placebo Arm:dapagliflozin placebo (oral tablet) and exenatide (5µg acutely)/Exenatide extended release (long term) placebo (subcutaneous injection) Placebo: 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 weeks0 / 110 / 110 / 11
Dapagliflozin Arm:dapagliflozin 10mg (oral tablet) and exenatide (5µg acutely)/Exenatide extended release (long term) placebo (subcutaneous injection) Dapagliflozin: 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 weeks0 / 150 / 150 / 15
Exenatide Extended Release Arm:subcutaneous injection of Exenatide (5µg acutely)/Exenatide extended release (long term) and dapagliflozin placebo Exenatide/Exenatide extended release: 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 weeks0 / 150 / 150 / 15
Exenatide Extended Release & Dapagliflozin Arm:Exenatide (5µg acutely)/Exenatide extended release (long term) and dapagliflozin 10mg Exenatide/Exenatide extended release: 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 Dapagliflozin: 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 weeks0 / 210 / 210 / 21

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years up to 65 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria: * 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 Exclusion Criteria: * 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: 1. Aspartate aminotransferase (AST) \>3x upper limit of normal (ULN) and/or alanine aminotransferase (ALT) \>3x ULN 2. Total bilirubin \>2.0 mg/dL (34.2 µmol/L) 3. Positive serologic evidence of current infectious liver disease including Hepatitis B viral antibody IGM, Hepatitis B surface antigen and Hepatitis C virus antibody 4. 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 * History of gastroparesis * History of medullary thyroid carcinoma or MEN 2 syndrome * History of recurring UTI * Uncontrolled thyroid disease (documented normal TSH), Cushing's syndrome, congenital adrenal hyperplasia or hyperprolactinemia. * Prior history of a malignant disease requiring chemotherapy or patients with a prior history of bladder cancer regardless of treatment * Alcoholism or drug addiction. * Hypertriglyceridemia (\>400 mg/dl). * Any other life-threatening, non-cardiac disease * Uncontrolled hypertension (BP \> 160/95 mm of Hg) * Patients with hypotension or at risk for volume depletion due to co-existing conditions or concomitant medications, such as loop diuretics or recently donated \>500ml of blood should have careful monitoring of their volume status * Pregnant or breastfeeding patients or patient not willing to use two barrier method contraception during study period (unless sterilized or have an IUD) * Use of hormonal medications, anti-obesity drugs or weight loss medications (prescription or OTC) and medications known to exacerbate glucose tolerance (such as isotretinoin, GnRH agonists, glucocorticoids, anabolic steroids, C-19 progestins) stopped for at least 8 weeks. Use of anti-androgens that act peripherally to reduce hirsutism such as 5-alpha reductase inhibitors (finesteride, spironolactone, flutamide) stopped for at least 4 weeks * Presence of hypersensitivity to dapagliflozin or other SGLT2 inhibitors (e.g. anaphylaxis, angioedema, exfoliative skin conditions * Known hypersensitivity or contraindications to use GLP1 receptor agonists (exenatide, liraglutide) * Known hypersensitivity to heparin/ IV catheter equipment. * Eating disorders (anorexia, bulimia) or gastrointestinal disorders * Having a history of bariatric surgery * Debilitating psychiatric disorder such as psychosis or neurological condition that might confound outcome variables * Use of an investigational agent or therapeutic regimen within 30 days of study * Participation in any other concurrent clinical trial

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