SGLT2 Inhibition: Uric Acid Excretion Study

Type 2 Diabetes Clinical Trial

— UREX  

Official title:

Uric Acid Excretion Study: Open-label Randomised Cross Over Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05210517
• Other study ID #: DCUREX2021
• Status: Completed
• Phase: Phase 4
• Start date: October 1, 2020
• Est. completion date: September 1, 2021

Study information

• Verified date: April 2023
• Source: Amsterdam UMC, location VUmc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The current study investigates the effects of SGLT2 inhibitor empagliflozin on uric acid excretion.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: September 1, 2021
• Est. primary completion date: June 8, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 35 Years to 75 Years

Eligibility

Inclusion Criteria:

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.

Exclusion Criteria:

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

Related Conditions & MeSH terms

• Type 2 Diabetes

Intervention

Drug:
• Empagliflozin 25 MG
25 once daily one week treatment
• Benzbromaron
100 mg once daily 1 one week treatment
• Empagliflozin 25 MG + benzbromarone 100 mg
combined treatment once daily for one week

Locations

Country	Name	City	State
Netherlands	VU University Medical Center	Amsterdam	Noord-Holland

Sponsors (1)

Lead Sponsor	Collaborator
Amsterdam UMC, location VUmc

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	plasma uric acid	change in plasma uric acid concentrations	1 week
Primary	Fractional uric acid excretion	change creatinine-adjusted fractional uric acid excretion	one week
Secondary	urinary glucose levels	glucose concentration urine	one week