ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12619000933156

Ethics application status

Approved

Date submitted

5/04/2016

Date registered

4/07/2019

Date last updated

24/11/2020

Date data sharing statement initially provided

4/07/2019

Type of registration

Retrospectively registered

Titles & IDs

Public title

Role of Magnetic Resonance Imaging (MRI) in evaluating the impact of Empagliflozin on kidneys in patients with Type 2 diabetes.

Scientific title

Using MRI to assess impact of add-on Empagliflozin on renal physiology in Type 2 diabetic patients

Secondary ID [1]

NONE

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Type 2 Diabetes Mellitus

Condition category

Condition code

Metabolic and Endocrine

Diabetes

Renal and Urogenital

Kidney disease

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Part 1: Healthy volunteers
Healthy volunteers have bloods taken to assess kidney function (estimated Glomerular Filtration rate) prior to MRI scan with injection of 0.05 mmol/kg Gadoterate meglumine (Dotarem, Aspen Pharmacare). Healthy volunteers are not required to take any medications as part of their participation, other than injection of contrast agent during the MRI scan.
The aim is to optimize a MRI protocol for comprehensive assessment to achieve high quality dynamic contrast enhanced imaging (DCE), phase contrast imaging (PC), arterial spin labelling (ASL), diffusion tensor imaging (DTI) and blood oxygen level dependent imaging (BOLD) imaging within a scan time of 1 hour.

Part 2: Patients with Type 2 Diabetes
Using a crossover design, patients will receive 12-14 weeks’ intervention with add-on oral empagliflozin 10mg tablet versus 50-100mg oral sitagliptin tablet daily in random order (n=18 commencing with empagliflozin, n=18 commencing with sitagliptin), with a 4-6 week washout period between interventions.
Empagliflozin has been dosed at 10mg daily as determined by the associate investigator Endocrinologist. Previous clinical trials have shown that patients who were prescribed Empagliflozin 10mg received the same benefits of SGLT2 inhibition as those prescribed Empagliflozin 25mg with less adverse events relating to Urinary Tract and genital infections. Patients receive one hour education face-to-face at screening and face-to-face at 5 hour study visits prior to commencement of the study drug about: the action of the drug, common, uncommon and rare adverse events, how and when to take the drug, how often to test BGL's, sign and symptoms of hypoglycaemia and how to manage a hypo., importance of maintaining adequate fluid and oral intake when taking empagliflozin due to potential for euglycaemic DKA.
In regular follow up telephone calls throughout the intervention, further education may be provided as required over the phone. A patient may be booked into diabetes clinic for endocrine review if experiencing significant adverse events.
The study nurse explains that patients are to keep the empty tablet packets to return at the following study visit. Tablet packets are then counted and documented in the patient file. The study nurse also maintains regular telephone contact with patients throughout the trial to monitor adherence and any adverse events reported. Weekly calls are maintained for the first 4 weeks of treatment, and then every 4 weeks until completion of the study drug unless in the event of adverse events. Adverse events are followed up until resolved. Weekly calls occur during the wash out phase to ensure patient does not experience uncontrolled hyperglycaemia. Following trial completion, patients are booked into the diabetes clinic within 4 weeks for medication review.

Sitagliptin will be dosed according to patients’ renal function, where 50mg sitagliptin will be prescribed to patients with eGFR less than 60ml/min/1.73m², and 100mg prescribed for patients with eGFR greater than or equal to 60ml/min/1.73m², in line with standard clinical care.

To summarise:
Visit 1 is the screening/ education visit.
Visits 2-5 are face to face 5 hour study visits where patients will undergo an MRI examination and blood tests as described in the protocol. Study drug education will be ongoing, with reinforcement regarding adverse effects, how and when to take the drug, etc. at visits 2 and 4 in particular.

With regard to the timing of the drug interventions:
Visit 2 – Baseline MRI examination/ blood tests for first drug administered (randomised to empagliflozin or sitagliptin)
Visit 3 – post drug MRI examination/ blood tests
Visit 4 – baseline MRI examination/ blood tests for second drug administered (after washout)
Visit 5 – post drug MRI examination/ blood tests

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Sitagliptin will be used as a comparator to distinguish effects of glucose lowering on GFR from independent effects of empagliflozin. Identical testing will be performed following each intervention period.

Control group

Active

Outcomes

Primary outcome [1]

The primary outcome measure for the clinical trial will be change in baseline MRI-derived Glomerular Filtration Rate (GFR) compared to MRI-derived Glomerular Filtration Rate (GFR) following 12-14 weeks empagliflozin to post-treatment.

Timepoint [1]