The renal effects of lixisenatide (a novel, gut-hormone based diabetes drug) and insulin glulisine (a common, wideley diabetes drug)

Phase 1

• Conditions: Type 2 Diabetes Mellitus; Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

• Registration Number: EUCTR2014-002178-35-NL
• Lead Sponsor: VU University Medical Center

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2014-08-05
• Last Update Posted: 25 November 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 40

Inclusion Criteria

•Type 2 diabetes mellitus
•Caucasian
•Both genders (females must be post-menopausal; no menses >1 year)
•Age: 35 - 75 years
•BMI: 25 - 40 kg/m2
•HbA1c: 6.5 - 10% DCCT (48 - 86 mmol/mol International Federation of Clinical Chemistry)
•Stable treatment with basal insulin glargine and metformin or basal insulin glargine alone
•Fasting plasma glucose (FPG) <10 mmol/L or the use of >50 units of basal insulin glargine
•Hypertension should be under control, i.e. <140/90 mmHg, and treated with a RAAS-interfering agent (ACE-I or ARB) for at least 3 months.
•Albuminuria should be treated with a RAAS-interfering agent (ACE-I or ARB) for at least 3 months.
•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 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40

Exclusion Criteria

•Current/chronic use of the following medication: TZD, SU derivative, GLP-1RA, DPP-4I, 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.
•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
•Hypoglycemia unawareness based on investigator judgment
•History of severe hypoglycemia that required emergency hospital treatment within 3 months prior to screening
•Estimated GFR <60 mL/min/1.73m2 (determined by the Modification of Diet in Renal Disease (MDRD) study equation)
•Pregnancy
•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
•Current atrial fibrillation
•Complaints compatible with or established gastroparesis, neurogenic bladder and/or incomplete bladder emptying (as determined by ultrasonic bladder scan)
•Active liver disease or a 3-fold elevation of liver enzymes (aspartate aminotransferase (AST)/alanine aminotransferase (ALT)) at screening
•History of or actual pancreatic disease
•History of or actual malignancy
•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 (i.e. GLP-1RA, inulin, metacresol (component lixisenatide and insulin glulisine), PAH, latex (component of PAH vial stopper))
•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

Primary Outcome Measures

Name	Time	Method
Main Objective: Primary objective: To assess the long-term effects (i.e. after 8-week drug exposure) of the GLP-1RA lixisenatide versus insulin glulisine on renal hemodynamics (glomerular filtration rate/effective renal plasma flow) in patients with type 2 diabetes;Secondary Objective: Secondary objectives: renal damage, renal tubular function, blood pressure;<br> Primary end point(s): To assess changes from baseline following 8-week treatment with a GLP-1RA versus a single dose of insulin on renal hemodynamics measured as:<br> •Glomerular filtration rate (measured by the inulin-clearance technique)<br> •Effective renal plasma flow (measured by the para-aminohippurate acid clearance technique)<br> ;Timepoint(s) of evaluation of this end point: Renal hemodynamics are assessed at baseline and after 8 weeks of treatment

Secondary Outcome Measures

Name	Time	Method
Timepoint(s) of evaluation of this end point: Secondary endpoints are assessed at baseline and after 8 weeks of treatment;<br> Secondary end point(s): To assess changes from baseline following 8-week treatment with a GLP-1RA versus a single dose of insulin on:<br> •Renal damage, measured by urine biomarkers as:<br> oUrinary albumin excretion (Glomerular)<br> oNeutrophil gelatinase-associated lipocalin and Kidney injury molecule-1 (Tubular)<br> •Renal tubular function, measured as:<br> oFractional sodium-, potassium-, chloride-, calcium-, magnesium-, phosphate- and urea excretion<br> oUrine osmolality<br> •Systolic blood pressure, diastolic blood pressure and mean arterial pressure (measured by oscillometric blood pressure device)<br>