Renohemodynamic Effects of Combined empagliflOzin and LosARta

Phase 1

• Conditions: Diabetes Mellitus type 2; Therapeutic area: Diseases [C] - Hormonal diseases [C19]

• Registration Number: EUCTR2019-003141-15-NL
• Lead Sponsor: Amsterdam University Medical Center - location VU Medical Center

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-06-17
• Last Update Posted: 8 October 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

•Caucasian*
•Both genders (females must be post-menopausal; no menses >1 year; in case of doubt, Follicle-Stimulating Hormone (FSH) will be determined with cut-off defined as >31 U/L)
•Age: 35 - 80 years
•BMI: >25 kg/m2
•HbA1c: 6.5 – 10.0% Diabetes Control and Complications Trial (DCCT) or 48 - 86 mmol/mol International Federation of Clinical Chemistry (IFCC)
•Treatment with a stable dose of metformin and/or SU therapy for at least 3 months prior to inclusion
•Written informed consent

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 12
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 12

Exclusion Criteria

•History of unstable or rapidly progressing renal disease
•Macroalbuminuria; defined as ACR of 300mg/g.
•Estimated GFR <60 mL/min/1.73m2 (determined by the Modification of Diet in Renal Disease (CKD-EPI) study equation)
•Only use of alpha blockers and/or beta blockers are allowed as antihypertensive background therapy. Patients using an antihypertensive agent will be considered if this agent can be stopped (i.e. blood pressure adequate to stop at screening) or replaced by an alpha and/or beta blocker. In these patients, a 4 week wash-out/run-in period will be observed prior to visit 2.
•Current/chronic use of the following medication: SGLT2 inhibitors, RAS inhibitors, TZD, GLP-1RA, DPP-4 inhibitors, glucocorticoids, immune suppressants, antimicrobial agents, chemotherapeutics, antipsychotics, tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs). Subjects on diuretics will only be excluded when these drugs cannot be stopped for the duration of the study.
•Volume depleted patients. Patients at risk for volume depletion due to co-existing conditions or concomitant medications, such as loop diuretics should have careful monitoring of their volume status.
•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 drug can be taken within a time-frame of 2 weeks prior to renal-testing
•History of diabetic ketoacidosis (DKA) requiring medical intervention (e.g. emergency room visit and/or hospitalization) within 1 month prior to the Screening visit.
•Current urinary tract infection and active nephritis
•Recent (<6 months) history of cardiovascular disease, including:
oAcute coronary syndrome
oChronic heart failure (New York Heart Association grade II-IV)
oStroke or transient ischemic neurologic disorder
•Complaints compatible with neurogenic bladder and/or incomplete bladder emptying (as determined by ultrasonic bladder scan)
•Severe hepatic insufficiency and/or significant abnormal liver function defined as aspartate aminotransferase (AST) >3x upper limit of normal (ULN) and/or alanine aminotransferase (ALT) >3x ULN
• (Unstable) thyroid disease; defined as fT4 outside of laboratory reference values or change in treatment within 3 months prior to screening visit
•History of or actual malignancy (except basal cell carcinoma)
•History of or actual severe mental disease
•Substance abuse (alcohol: defined as >4 units/day)
•Allergy to any of the agents used in the study
•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
•Inability to understand the study protocol or give informed consent

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified