Type 2 DiabetesPhase 4UREXNCT05210517
SGLT2 Inhibition: Uric Acid Excretion Study
A Phase 4 study testing Empagliflozin 25 MG, Benzbromaron and Empagliflozin 25 MG + benzbromarone 100 mg in people with Type 2 Diabetes, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
Trial summary
The current study investigates the effects of SGLT2 inhibitor empagliflozin on uric acid excretion. Read more about this study
- Who is it for?
- Ages 35 to 75 years
- Conditions the study is for
- Type 2 Diabetes
- What is being tested?
- Empagliflozin 25 MG, Benzbromaron and Empagliflozin 25 MG + benzbromarone 100 mg
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Oct 2020to 1 Sep 2021
- Phase
- Phase 4
- 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 35 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Caucasian Men or post-menopausal women Age 35 to 75 Diagnosed with T2D HbA1c from 6.5% to 9.0% (48-75 mmol/mol) body mass index >25 kg/m2 Treated with metformin monotherapy (stable dose for ≥3 months) with or without sulfonylurea Well-controlled blood pressure (i.e., <140/90 mm Hg). In case of previously diagnosed hypertension and/or albuminuria treatment at least a stable dose of a renin-angiotensin system (RAS) inhibitor for ≥3 months at maximal tolerable dose.
Who cannot join
- History of gout history of unstable or rapidly progressing renal or malignant disease (excluding basal cell carcinoma) eGFR <60 mL/min/1.73 m2 Estimated GFR <45 mL/min/1.73m2 (determined by the Modification of Diet in Renal Disease (MDRD) study equation) Hemoglobin level < 7.0 mmol/L Current urinary tract infection and active nephritis Macroalbuminuria; defined as ACR of >300 mg/g. Current/chronic use of the following medication: thiazolidinediones, sulfonylurea derivatives, GLP-1 receptor agonists, DPP-4 inhibitors, SGLT-2 inhibitor, oral glucocorticoids, immune suppressants, antimicrobial agents, chemotherapeutics, antipsychotics, tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MOAIs).
- Patients on diuretics will only be excluded when these drugs cannot be stopped 3 months prior randomization and for the duration of the study.
- Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) will not be allowed, unless used as incidental medication (1-2 tablets) for non-chronic indications (i.e. sports injury, head-ache or back ache). However, no such drugs can be taken within a time-frame of 2 weeks prior to renal-testing Pregnancy History of or actual severe mental disease History of or actual severe somatic disease (e.g. systemic disease) History of or actual malignancy (except basal cell carcinoma) History of or actual pancreatic disease (Unstable) thyroid disease Severe hepatic insufficiency and/or significant abnormal liver function defined as aspartate aminotransferase (AST) >3x upper limit of normal (ULN) Recent (<6 months) history of cardiovascular disease, including Acute coronary syndrome Stroke or transient ischemic neurologic disorder or chronic heart failure (NYHA grade II-IV) Complaints compatible with or established neurogenic bladder and/or incomplete bladder emptying (as determined by ultrasonic bladder scan) Substance abuse (alcohol: defined as >3 units alcohol/day) History of diabetic ketoacidosis (DKA) requiring medical intervention (e.g., emergency room visit and/or hospitalization) within 1 month prior to the Screening visit.
- Recent blood donation (< 6 months) Allergy to any of the agents used in the study Inability to understand the protocol and/or give informed consent Individuals who are investigator site personnel, directly affiliated with the study, or are immediate (spouse, parent, child, or sibling, whether biological or legally adopted) family of investigator site personnel directly affiliated with the study
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
VU University Medical Center
Amsterdam, North Holland, 1081HV
About this study
Official title: Uric Acid Excretion Study: Open-label Randomised Cross Over Study
The current study investigates the effects of SGLT2 inhibitor empagliflozin on uric acid excretion.
Read the detailed description
SGTL2 inhibitors improve cardiovascular and kidney outcomes. The underlying mechanisms are incompletely understood. SGLT2 inhibitors are known to reduce plasma uric acid likely by enhanced urinary uric acid excretion.
In this study the investigators will study the effects of SGLT2 inhibit on uric acid levels and excretion in detail, linking it to the role of glucosuria and Uric acid transporter (URAT1) which in rodents was indispensable for the glucose-lowering effects of SGLT2 inhibition.
- Conditions
- Type 2 Diabetes
- Being tested
- Empagliflozin 25 MG, Benzbromaron, Empagliflozin 25 MG + benzbromarone 100 mg
- 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.
Empagliflozin 25 MGDrug
25 once daily one week treatment
BenzbromaronDrug
100 mg once daily 1 one week treatment
Empagliflozin 25 MG + benzbromarone 100 mgDrug
combined treatment once daily for one week
| Study group | Role | What they receive |
|---|---|---|
| No intervention | No intervention | Not described |
| Empagliflozin | Experimental | Empagliflozin 25 mg once daily for one week Receives: Drug: Empagliflozin 25 MG |
| Benzbromarone | Experimental | Benzbromarone 100 mg once daily for one week Receives: Drug: Benzbromaron |
| Empagliflozin-Benzbromarone | Experimental | Empagliflozin 25 mg once daily for one week combined with Benzbromarone 100 mg once daily for one week Receives: Drug: Empagliflozin 25 MG + benzbromarone 100 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
plasma uric acid
change in plasma uric acid concentrations
Measured: 1 week
Fractional uric acid excretion
change creatinine-adjusted fractional uric acid excretion
Measured: one week
Secondary outcomes (1)
urinary glucose levels
glucose concentration urine
Measured: one week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2022
- Study start1 Oct 2020
- Primary completion8 Jun 2021
- Study completion1 Sep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
- More trials run by Amsterdam UMC, location VUmcThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- 4-arm cross over, open label intervention study
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amsterdam UMC, location VUmc
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, D van Raalte, Amsterdam UMC, location VUmc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05210517
- Sponsor's protocol ID
- DCUREX2021
- Acronym
- UREX
- Status last verified
- Apr 2023
- First submitted
- 13 Jan 2022
- Last updated
- 1 May 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Suijk DLS, van Baar MJB, van Bommel EJM, Iqbal Z, Krebber MM, Vallon V, Touw D, Hoorn EJ, Nieuwdorp M, Kramer MMH, Joles JA, Bjornstad P, van Raalte DH. SGLT2 Inhibition and Uric Acid Excretion in Patients with Type 2 Diabetes and Normal Kidney Function. Clin J Am Soc Nephrol. 2022 May;17(5):663-671. doi: 10.2215/CJN.11480821. Epub 2022 Mar 23.
PubMed 35322793
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Uric Acid Excretion Study: Open-label Randomised Cross Over Study
- ClinicalTrials.gov ID
- NCT05210517
- Acronym / sponsor ID
- UREX / DCUREX2021
- Conditions
- Type 2 Diabetes
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Amsterdam UMC, location VUmcUniversity, hospital or other
- Study start
- 1 Oct 2020 (actual)
- Primary completion
- 8 Jun 2021 (actual)
- Study completion
- 1 Sep 2021 (actual)
- First posted
- 27 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The current study investigates the effects of SGLT2 inhibitor empagliflozin on uric acid excretion.
Detailed description
SGTL2 inhibitors improve cardiovascular and kidney outcomes. The underlying mechanisms are incompletely understood. SGLT2 inhibitors are known to reduce plasma uric acid likely by enhanced urinary uric acid excretion.
In this study the investigators will study the effects of SGLT2 inhibit on uric acid levels and excretion in detail, linking it to the role of glucosuria and Uric acid transporter (URAT1) which in rodents was indispensable for the glucose-lowering effects of SGLT2 inhibition.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- 4-arm cross over, open label intervention study
| Arm | Type | Receives |
|---|---|---|
| No intervention | No intervention | – |
| Empagliflozin | Experimental | Drug: Empagliflozin 25 MGEmpagliflozin 25 mg once daily for one week |
| Benzbromarone | Experimental | Drug: BenzbromaronBenzbromarone 100 mg once daily for one week |
| Empagliflozin-Benzbromarone | Experimental | Drug: Empagliflozin 25 MG + benzbromarone 100 mgEmpagliflozin 25 mg once daily for one week combined with Benzbromarone 100 mg once daily for one week |
Who may qualify
- Ages
- 35 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Caucasian Men or post-menopausal women Age 35 to 75 Diagnosed with T2D HbA1c from 6.5% to 9.0% (48-75 mmol/mol) body mass index >25 kg/m2 Treated with metformin monotherapy (stable dose for ≥3 months) with or without sulfonylurea Well-controlled blood pressure (i.e., <140/90 mm Hg). In case of previously diagnosed hypertension and/or albuminuria treatment at least a stable dose of a renin-angiotensin system (RAS) inhibitor for ≥3 months at maximal tolerable dose.
Key exclusion criteria (4 listed)
- History of gout history of unstable or rapidly progressing renal or malignant disease (excluding basal cell carcinoma) eGFR <60 mL/min/1.73 m2 Estimated GFR <45 mL/min/1.73m2 (determined by the Modification of Diet in Renal Disease (MDRD) study equation) Hemoglobin level < 7.0 mmol/L Current urinary tract infection and active nephritis Macroalbuminuria; defined as ACR of >300 mg/g. Current/chronic use of the following medication: thiazolidinediones, sulfonylurea derivatives, GLP-1 receptor agonists, DPP-4 inhibitors, SGLT-2 inhibitor, oral glucocorticoids, immune suppressants, antimicrobial agents, chemotherapeutics, antipsychotics, tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MOAIs).
- Patients on diuretics will only be excluded when these drugs cannot be stopped 3 months prior randomization and for the duration of the study.
- Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) will not be allowed, unless used as incidental medication (1-2 tablets) for non-chronic indications (i.e. sports injury, head-ache or back ache). However, no such drugs can be taken within a time-frame of 2 weeks prior to renal-testing Pregnancy History of or actual severe mental disease History of or actual severe somatic disease (e.g. systemic disease) History of or actual malignancy (except basal cell carcinoma) History of or actual pancreatic disease (Unstable) thyroid disease Severe hepatic insufficiency and/or significant abnormal liver function defined as aspartate aminotransferase (AST) >3x upper limit of normal (ULN) Recent (<6 months) history of cardiovascular disease, including Acute coronary syndrome Stroke or transient ischemic neurologic disorder or chronic heart failure (NYHA grade II-IV) Complaints compatible with or established neurogenic bladder and/or incomplete bladder emptying (as determined by ultrasonic bladder scan) Substance abuse (alcohol: defined as >3 units alcohol/day) History of diabetic ketoacidosis (DKA) requiring medical intervention (e.g., emergency room visit and/or hospitalization) within 1 month prior to the Screening visit.
- Recent blood donation (< 6 months) Allergy to any of the agents used in the study Inability to understand the protocol and/or give informed consent Individuals who are investigator site personnel, directly affiliated with the study, or are immediate (spouse, parent, child, or sibling, whether biological or legally adopted) family of investigator site personnel directly affiliated with the study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Empagliflozin 25 MG25 once daily one week treatment | Drug | Empagliflozin |
| Benzbromaron100 mg once daily 1 one week treatment | Drug | Benzbromarone |
| Empagliflozin 25 MG + benzbromarone 100 mgcombined treatment once daily for one week | Drug | Empagliflozin-Benzbromarone |
Primary outcome
plasma uric acid
Time frame: 1 week
change in plasma uric acid concentrations
Fractional uric acid excretion
Time frame: one week
change creatinine-adjusted fractional uric acid excretion
1 secondary outcome
urinary glucose levels
Time frame: one week
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2023.
- Derived from this study: PubMed 35322793Suijk DLS, van Baar MJB, van Bommel EJM, Iqbal Z, Krebber MM, Vallon V, Touw D, Hoorn EJ, Nieuwdorp M, Kramer MMH, Joles JA, Bjornstad P, van Raalte DH. SGLT2 Inhibition and Uric Acid Excretion in Patients with Type 2 Diabetes and Normal Kidney Function. Clin J Am Soc Nephrol. 2022 May;17(5):663-671. doi: 10.2215/CJN.11480821. Epub 2022 Mar 23.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Empagliflozin 25 MG, Benzbromaron and Empagliflozin 25 MG + benzbromarone 100 mg in people with Type 2 Diabetes, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
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 1 inclusion and 4 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: finished, as of the sponsor's last update on 1 May 2023. 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 Netherlands. 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
plasma uric acid (time frame: 1 week). The study lists 2 primary outcomes in all. 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 NCT05210517, 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 1 May 2023.