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Trial registered on ANZCTR


Registration number
ACTRN12621000829819
Ethics application status
Approved
Date submitted
7/05/2021
Date registered
29/06/2021
Date last updated
29/06/2021
Date data sharing statement initially provided
29/06/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
The effect of sodium-glucose transport protein 2 inhibitor and fibrate therapies, alone and in combination, on the serum uric acid concentration in hyperuricaemic people with type 2 diabetes
Scientific title
The effect of sodium-glucose transport protein 2 inhibitor and fibrate therapies, alone and in combination, on the serum uric acid concentration in hyperuricaemic people with type 2 diabetes
Secondary ID [1] 304168 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 diabetes 321861 0
Hyperuricaemia 321862 0
Condition category
Condition code
Metabolic and Endocrine 319587 319587 0 0
Diabetes
Metabolic and Endocrine 319902 319902 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Each participant will be randomised by computer-generated code to receive empagliflozin 25 mg daily orally for one week, fenofibrate 145 mg daily orally for one week, or the combination of empagliflozin 25 mg and fenofibrate 145 mg daily for one week, with each active treatment period separated by a one-week washout period. Tablet checks will be done at each of each active treatment period.
Intervention code [1] 320498 0
Treatment: Drugs
Comparator / control treatment
This is a crossover randomised trial with the participants acting as their own controls. The reference comparatory intervention will be each drug given individually compared when both are taken together.
Control group
Active

Outcomes
Primary outcome [1] 327444 0
Change in fasting serum uric acid
Timepoint [1] 327444 0
Before and after one week of randomly allocated therapy (empagliflozin alone, fenofibrate alone, and empagliflozin plus fenofibrate).
Secondary outcome [1] 395146 0
Acute change in serum uric acid concentration
Timepoint [1] 395146 0
Before dosing and 6 hours after dosing, before and after one week of randomly allocated therapy (empagliflozin alone, fenofibrate alone, and empagliflozin plus fenofibrate).
Secondary outcome [2] 395147 0
Fasting serum uric acid <0.36 mmol/L at the end of treatment
Timepoint [2] 395147 0
After a week of randomly allocated therapy (empagliflozin alone, fenofibrate alone, and empagliflozin plus fenofibrate).
Secondary outcome [3] 395148 0
Change in estimated glomerular filtration rate (eGFR) measured from the serum creatinine and using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation.
Timepoint [3] 395148 0
Before and after one week of randomly allocated therapy (empagliflozin alone, fenofibrate alone, and empagliflozin plus fenofibrate).

Eligibility
Key inclusion criteria
• Type 2 diabetes diagnosed at least 3 months previously and treated with stable oral blood glucose lowering therapies
• Age between 18 and 70 years apart from women of child-bearing age who will be excluded.
• Body mass index between 20 and 40 kg/m²
• Glycated haemoglobin >6.5% and <9.0%
• Hyperuricaemia (serum uric acid above the upper limit of the laboratory reference range i.e. greater than to equal to 0.42 mmol/L)
• No current therapy with either an SGLT2i or a fibrate, or allopurinol or febuxostat
• No history of intolerance or adverse effects with past use of an SGLT2i or a fibrate
• No contraindications to SGLT2i or fibrate use including renal impairment (eGFR <45 mL/min), past history of recurrent genitourinary infections and/or symptomatic postural hypotension
• Stable doses of any medications (such as aspirin and thiazide diuretics) known to influence serum uric acid concentrations
• Stable alcohol intake of <3 standard drinks/day
• No recent history of smoking
• No significant co-morbidity such as cancer or mental health issues that would affect the ability to follow a normal lifestyle and take regular medications including allocated
• Ability to provide written informed consent and to attend all scheduled study assessments
Minimum age
18 Years
Maximum age
70 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Type 1 or other non-Type 2 forms of diabetes
• Diagnosed within the last 3 months
• Recent changes in oral blood glucose lowering therapies
• Age lower than 18 years and greater than 70 years
• Women of child-bearing age
• Body mass index below 20 and greater than40 kg/m²
• Glycated haemoglobin <6.5% and >9.0%
• Normal serum uric acid (below the upper limit of the laboratory reference range or <0.42 mmol/L)
• Current therapy with either an SGLT2i or a fibrate, or allopurinol or febuxostat
• A history of intolerance or adverse effects with past use of an SGLT2i or a fibrate
• Contraindications to SGLT2i or fibrate use including renal impairment (eGFR <45 mL/min), past history of recurrent genitourinary infections and/or symptomatic postural hypotension
• Unstable doses of any medications (such as aspirin and thiazide diuretics) known to influence serum uric acid concentrations
• Alcohol intake of >3 standard drinks/day
• Recent smoking
• Significant co-morbidity such as cancer or mental health issues that would affect the ability to follow a normal lifestyle and take regular medications including allocated
• Inability to provide written informed consent and to attend all scheduled study assessments

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Open label study
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Sequence generation will be by randomised by computer-generated code
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 4
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Sample size: Although a pilot study, the 10 participants in this crossover study will ensure that a true difference in the change in fasting serum uric acid between combination fenofibrate/empagliflozin compared to each of the two other individual treatment arms of =0.04 mmol/L will be detected with a probability of 0.80 and two-sided 0.05 significance level based on the assumption that the standard deviation of the difference in the response variables is 0.04 mmol/L. Although withdrawal is very unlikely based on the low risk of significant side-effects with both therapies, participants who are unable to complete all study procedures (dosing and blood samples) due to tolerability issues or who cannot fulfil study requirements because of work or personal circumstances will be replaced to maintain the sample size required.

Differences in the change in fasting serum uric acid between the three allocated treatments will be assessed using Analysis of Covariance adjusting for differences in baseline serum uric acid between treatments. The same approach will be used to assess treatment effects on eGFR.
Differences in proportions of participants achieving a serum uric acid <0.36 mmol/L after a week of therapy will be assessed using a Chi-squared test. Differences in the change in serum uric acid from 0 to 6 hours at the beginning and end of each week-long treatment period will be analysed using Generalised Linear Modelling.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 19347 0
Fremantle Hospital and Health Service - Fremantle
Recruitment hospital [2] 19348 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 33930 0
6160 - Fremantle
Recruitment postcode(s) [2] 33931 0
6150 - Murdoch

Funding & Sponsors
Funding source category [1] 308547 0
Charities/Societies/Foundations
Name [1] 308547 0
Arthitis Australia
Address [1] 308547 0
Level 2/255 Broadway
GLEBE NSW 2037
Country [1] 308547 0
Australia
Primary sponsor type
Individual
Name
Timothy Davis
Address
University of Western Australia, Medical School, Fremantle Hospital, PO Box 480, Fremantle, Western Australia 6959
Country
Australia
Secondary sponsor category [1] 309397 0
Individual
Name [1] 309397 0
Helen Keen
Address [1] 309397 0
University of Western Australia, Medical School, Fiona Stanley Hospital, 11 Robin Warren Dr, Murdoch WA 6150
Country [1] 309397 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308493 0
University of Western Australia Human Research Ethics Committee
Ethics committee address [1] 308493 0
University of Western Australia, 35 Stirling Hwy, Crawley, WA 6009
Ethics committee country [1] 308493 0
Australia
Date submitted for ethics approval [1] 308493 0
03/02/2021
Approval date [1] 308493 0
24/05/2021
Ethics approval number [1] 308493 0
2021/ET000063

Summary
Brief summary
Gout is the result of high levels of uric acid in the blood depositing in the joints. It can also deposit in the kidneys and is associated with kidney disease, cardiovascular disease and death. The treatment for gout is tablets that lower uric acid in the blood stream, but most people with gout aren’t prescribed uric acid lowering therapies, or simply don’t take their medications. People with diabetes have are more at risk of developing gout than people without diabetes, due to high levels of uric acid in the blood. This study aims to identify the extent to which current diabetes medications may lower uric acid; with the hope of avoiding the need to add additional therapies to treat gout in people who already take many medicines. This is likely to increase adherence to gout therapy in people with diabetes, improving outcomes and decreasing the long term complications of gout including joint pain and death form cardiovascular disease.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 110894 0
Prof Timothy Davis
Address 110894 0
University of Western Australia, Medical School, Fremantle Hospital, PO Box 480, Fremantle, Western Australia 6959
Country 110894 0
Australia
Phone 110894 0
+61 8 94313229
Fax 110894 0
Email 110894 0
tim.davis@uwa.edu.au
Contact person for public queries
Name 110895 0
Prof Timothy Davis
Address 110895 0
University of Western Australia, Medical School, Fremantle Hospital, PO Box 480, Fremantle, Western Australia 6959
Country 110895 0
Australia
Phone 110895 0
+61 8 9431 3229
Fax 110895 0
Email 110895 0
tim.davis@uwa.edu.au
Contact person for scientific queries
Name 110896 0
Prof Timothy Davis
Address 110896 0
University of Western Australia, Medical School, Fremantle Hospital, PO Box 480, Fremantle, Western Australia 6959
Country 110896 0
Australia
Phone 110896 0
+61 8 94313229
Fax 110896 0
Email 110896 0
tim.davis@uwa.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Basic baseline demographic details and serum uric concentrations during the trial
When will data be available (start and end dates)?
March 2022 to December 2022
Available to whom?
Researchers with a genuine interest in utilising the data for further research including met-analyses
Available for what types of analyses?
Novel statistical analyses of study data or meta-analysis with other data sources
How or where can data be obtained?
From the Principal Investigator on reasonable request (email tim.davis@uwa.edu.au)
What supporting documents are/will be available?
Study protocol
Informed consent form
Ethical approval
How or where can supporting documents be obtained?
Type [1] 11613 0
Study protocol
Citation [1] 11613 0
Link [1] 11613 0
Email [1] 11613 0
tim.davis@uwa.edu.au
Other [1] 11613 0
Type [2] 11615 0
Informed consent form
Citation [2] 11615 0
Link [2] 11615 0
Email [2] 11615 0
tim.davis@uwa.edu.au
Other [2] 11615 0
Type [3] 12280 0
Ethical approval
Citation [3] 12280 0
Link [3] 12280 0
Email [3] 12280 0
Other [3] 12280 0
Summary results
No Results