SGLT2 Inhibition: Uric Acid Excretion Study

NCT05210517 | Completed Phase 4

• 1 other identifier: DCUREX2021
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Type 2 Diabetes

Outcome Measures

Primary Outcomes (2)

• plasma uric acid

  change in plasma uric acid concentrations

  1 week

• Fractional uric acid excretion

  change creatinine-adjusted fractional uric acid excretion

  one week

Secondary Outcomes (1)

• urinary glucose levels

  one week

Study Arms (4)

No intervention

NO INTERVENTION

Empagliflozin

EXPERIMENTAL

Empagliflozin 25 mg once daily for one week

Drug: Empagliflozin 25 MG

Benzbromarone

EXPERIMENTAL

Benzbromarone 100 mg once daily for one week

Drug: Benzbromaron

Empagliflozin-Benzbromarone

EXPERIMENTAL

Empagliflozin 25 mg once daily for one week combined with Benzbromarone 100 mg once daily for one week

Drug: Empagliflozin 25 MG + benzbromarone 100 mg

Interventions

Empagliflozin 25 MG DRUG

25 once daily one week treatment

Empagliflozin

Benzbromaron DRUG

100 mg once daily 1 one week treatment

Benzbromarone

Empagliflozin 25 MG + benzbromarone 100 mg DRUG

combined treatment once daily for one week

Empagliflozin-Benzbromarone

Eligibility Criteria

• Age: 35 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Amsterdam UMC, location VUmc: lead

Study Sites (1)

VU University Medical Center

Amsterdam, North Holland, 1081HV, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 35322793 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

empagliflozin; Benzbromarone

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD PhD, associate professor of medicine, internist-endocrinologist

Model Details: 4-arm cross over, open label intervention study

Study Record Dates

• First Submitted: January 13, 2022
• First Posted: January 27, 2022
• Study Start: October 1, 2020
• Primary Completion: June 8, 2021
• Study Completion: September 1, 2021
• Last Updated: May 1, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)