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Type 2 DiabetesPhase 2NCT02558270

Effects of SGLT-2 Inhibition on Hepatic Glucose and Energy Metabolism

A Phase 2 study testing Dapagliflozin in people with Type 2 Diabetes and Metabolically Healthy Controls, run by Medical University of Vienna at 1 site in Austria.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

Inhibition of SGLT2 by specific inhibitors has been shown to reduce the renal threshold for glucose excretion in patients with type 2 diabetes mellitus (T2DM) and control subjects leading to significant renal glucose loss even in the presence of normal glucose concentrations. Read more about this study

Who is it for?
Ages 18 to 75 yearsHealthy volunteers can take part
What is being tested?
Dapagliflozin
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
20 participants
Where
1 siteAustria
Study dates
Jun 2016to Jun 2018
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Type 2 diabetes
  • BMI 23 - 35 kg/m2
  • Age between 18 - 75 years
  • HbA1c < 7.5% while on dietary treatment only or treatment!with!up!to!two!oral!antidiabetic! agents!including!metformin,!alphaAglucosidase!inhibitor,!sulfonyl!urea!or!DPPAIV!inhibitor.
  • Must have given written informed consent and be able to comply with all study requirements
  • Males or females. Aged 18 to 75 years, inclusive, at the time of informed consent
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  • Females: Non-pregnant and non-lactating; surgically sterile (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy), post-menopausal (defined as 12 months of spontaneous amenorrhea in females > 55 years of age or, in females ≤ 55 years, 12 months of spontaneous amenorrhea without an alternative medical cause and FSH levels in the postmenopausal range for the laboratory involved), abstinent, or if engaged in sexual relations of child-bearing potential, subject is using an acceptable contraceptive method.
  • Body Mass Index (BMI) 23 - 35 kg/m2
  • Agree to maintain current diet and exercise regimen. Agree to abstain from alcoholic beverages for at least 48 hours prior to clinic visits and not increase alcohol consumption during the study

Who cannot join

  • smoking
  • pregnancy
  • treatment with more than 2 oral antidiabetic agents or treatment with insulin / SGLT2 inhibitor
  • regular medication
  • tendency towards claustrophobia
  • metal devices or other magnetic material in or on the subjects body which will be hazardous for NMR investigation [heart pacemaker, brain (aneurysm) clip, nerve stimulators, electrodes, ear implants, post coronary by-pass graft (epicardial pace wires), penile implants, colored contact lenses, patch to deliver medications through the skin, coiled spring intrauterine device, vascular filter for blood clots, orthodontic braces, shunt-spinal or ventricular, any metal implants (rods, joints, plates, pins, screws, nails, or clips), embolization coil, or any metal fragments or shrapnel in the body].
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  • 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
  • Creatinine Clearance: <60 mL/min (calculated by Cockcroft-Gault formula) or a measured serum creatinine value of >1.5 mg/dL (133 μmol/L) for male patients and >1.4 mg/dL (124 μmol/L) for female patients, History of unstable or rapidly progressing renal disease
  • History of diabetic ketoacidosis (DKA) requiring medical intervention (eg, emergency room visit and/or hospitalization) within 1 month prior to the Screening visit.
  • Volume depleted patients.
  • Recent Cardiovascular Events in a patient:
  • Acute Coronary Syndrome (ACS) within 2 months prior to enrolment
  • Hospitalization for unstable angina or acute myocardial infarction within 2 months prior to enrolment
  • Acute Stroke or TIA within two months prior to enrolment
  • Less than two months post coronary artery revascularization
  • Congestive heart failure defined as New York Heart Association (NYHA) class IV, unstable or acute congestive heart failure.
  • Treatment with insulin, thiazolidinedione (e.g., pioglitazone), GLP-1 agonist, SGLT2 and other drugs that may affect plasma glucose level (including systemic glucocorticoids) within 3 months prior to screening
  • Clinically!significant!abnormalities!in!medical!history!or!physical!examination + smoking
  • regular medication
  • pregnancy, breast feeding
  • tendency towards claustrophobia
  • metal devices or other magnetic material in or on the subjects body which will be hazardous for NMR investigation [heart pacemaker, brain (aneurysm) clip, nerve stimulators, electrodes, ear implants, post coronary by-pass graft (epicardial pace wires), penile implants, colored contact lenses, patch to deliver medications through the skin, coiled spring intrauterine device, vascular filter for blood clots, orthodontic braces, shunt-spinal or ventricular, any metal implants (rods, joints, plates, pins, screws, nails, or clips), embolization coil, or any metal fragments or shrapnel in the body].
  • 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
  • Creatinine Clearance: <60 mL/min (calculated by Cockcroft-Gault formula) or a measured serum creatinine value of >1.5 mg/dL (133 μmol/L) for male patients and >1.4 mg/dL (124 μmol/L) for female patients, History of unstable or rapidly progressing renal disease
  • Volume depleted patients. Patients at risk for volume depletion due to co-existing conditions

Trial locations and contacts

1 site in 1 country.

Michael Krebs, Prof. MD contact

0140400/431000

michael.krebs@meduniwien.ac.at

Austria1 site, 1 recruiting

  • Medical University Of Vienna, Department of Internal Medicine III

    Vienna, State of Vienna, 1090

    Peter Wolf, MD, 004314040043110, peter.wolf@meduniwien.ac.at

    Recruiting

Other trials in Austria

About this study

Official title: Acute Effects of Sodium GlucOse Co-Transporter 2 (SGLT2) Inhibition on Hepatic Glucose and Energy Metabolism

Inhibition of SGLT2 by specific inhibitors has been shown to reduce the renal threshold for glucose excretion in patients with type 2 diabetes mellitus (T2DM) and control subjects leading to significant renal glucose loss even in the presence of normal glucose concentrations. SGLT2 inhibition with canagliflozin induces a 24h urinary glucose loss of around 70g in healthy subjects.

Recent studies indicate that under fasting and postprandial conditions administration of SGLT-2 inhibitors leads to increase in endogenous (hepatic) glucose production (EGP) potentially counteracting the glucose lowering potency of these drugs. Dapagliflozin has been shown to acutely increase endogenous glucose production (EGP) and plasma glucagon concentrations under postabsorptive conditions within 2 hours after drug ingestion in patients with (T2DM). Glucagon binds to receptors in the liver and activates hepatic gluconeogenesis (GNG) and glycogenolysis, likely contributing to the observed increase in EGP.

So far the likely interrelation between acute changes in hepatic glucose metabolism and energy turnover contributing to increased hepatic glucose production induced by SGLT2 inhibition has not been studied. It is known that out of the 80% of oxygen consumption coupled to ATP synthesis, 7- 10% is used by GNG. However, so far the effects of dapagliflozin on acute changes in gluconeogenesis (GNG) and ATP turnover in hepatic tissue and on the time course of hormones involved in hypoglycaemia counter regulation have not been studied.

Being tested
Dapagliflozin, Placebo
Medical subject headings
Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT02558270
Study groupRoleWhat they receive
patients dapaActive comparatorPatients will be administered Dapagliflozin 10mg
Receives: Drug: Dapagliflozin
patients placeboPlacebo comparatorPatients will be administered a placebo
Receives: Drug: Placebo
controls dapaActive comparatorcontrols will be administered Dapagliflozin 10mg
Receives: Drug: Dapagliflozin
controls placeboPlacebo comparatorcontrols will be administered a placebo
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in endogenous glucose production

    Measured: 420 minutes

Secondary outcomes (5)

  1. Change in hepatic gluconeogenesis

    Measured: 420 minutes

  2. Change in hepatic lipid content

    Measured: 420 minutes

  3. Change in hepatic glycogen content

    Measured: 420 minutes

  4. Changes in hepatic ATP concentrations

    Measured: 420 minutes

  5. Changes in hormones involved in hypoglycemia counter regulation

    Measured: 420 minutes

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Sep 2015 (estimated)
  2. Study startJun 2016
  3. Primary completionDec 2017 (estimated)
  4. Study completionJun 2018 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
20 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02558270
Sponsor's protocol ID
GOETHE_V2
Status last verified
Sep 2016
First submitted
22 Sep 2015
Last updated
27 Sep 2016
Results posted
No
Data monitoring committee
Yes

Publications

  • Wolf P, Fellinger P, Pfleger L, Beiglbock H, Krumpolec P, Barbieri C, Gastaldelli A, Harreiter J, Metz M, Scherer T, Zeyda M, Baumgartner-Parzer S, Marculescu R, Trattnig S, Kautzky-Willer A, Krssak M, Krebs M. Gluconeogenesis, But Not Glycogenolysis, Contributes to the Increase in Endogenous Glucose Production by SGLT-2 Inhibition. Diabetes Care. 2021 Feb;44(2):541-548. doi: 10.2337/dc20-1983. Epub 2020 Dec 14.

    PubMed 33318126

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Dapagliflozin in people with Type 2 Diabetes and Metabolically Healthy Controls, run by Medical University of Vienna at 1 site in Austria.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 27 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Michael Krebs, Prof. MD (0140400/431000, michael.krebs@meduniwien.ac.at), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in endogenous glucose production (time frame: 420 minutes). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02558270, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Sep 2016.

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