DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more

Effect of LIXIsenatide on the Renal System

Information source: VU University Medical Center
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Diabetic Kidney Disease; Diabetic Nephropathy; Diabetes Mellitus; Glucagon-Like Peptide 1

Intervention: Lixisenatide (Drug); Insulin glulisine (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: VU University Medical Center


Based on preclinical and small-sized studies in non-diabetic individuals, incretin-based therapies, i. e. glucagon-like peptide (GLP)-1 receptor agonists and dipeptidyl peptidase-4 inhibitors, may hold promise in preventing the onset and progression of diabetic kidney disease. However, the potential renoprotective effects of these agents, that are believed to be effectuated "beyond glucose control", have not been sufficiently detailed in human diabetes. Therefore, the present study aims to explore the mechanistic and clinical effects of GLP-1 receptor agonists on renal physiology and biomarkers in patients with type 2 diabetes. Forty patients with insulin-treated type 2 diabetes will undergo an eight week intervention with lixisenatide or insulin glulisine in order to assess changes in the outcome parameters.

Clinical Details

Official title: A Phase 4, Mono-center, Randomized, Open Label, Comparator-controlled, Parallel-group, Mechanistic Intervention Trial to Assess the Effect of 8-week Treatment With the Glucagon-like Peptide-1 Receptor Agonist Lixisenatide Versus Insulin Glulisine on Renal Physiology and Biomarkers in Insulin Glargine-treated Patients With Type 2 Diabetes Mellitus

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Changes from baseline following 8-week treatment with a glucagon-like peptide(GLP)-1 receptor agonist versus insulin glulisine on renal hemodynamics, measured as glomerular filtration rate (GFR) / effective renal plasma flow (ERPF)

Secondary outcome:

Renal damage, measured by urine biomarkers

Renal tubular function

Blood Pressure


Minimum age: 35 Years. Maximum age: 75 Years. Gender(s): Both.


Inclusion Criteria:

- Patients with type 2 diabetes (HbA1c: 6. 5-10. 0% or 48-86 mmol/mol)

- Stable treatment with basal insulin glargine (dose ±20%) and metformin or basal

insulin glargine (dose ±20%) alone for at least 3 months

- Fasting plasma glucose <10 mmol/L or the use of >50 units of basal insulin glargine

- Females must be post-menopausal

- Caucasian

- Age: 35 - 75 years

- Body Mass Index: >25 kg/m2

- Hypertension should be under control, i. e. <140/90 mmHg, and treated with an

angiotensin-converting enzyme inhibitor or angiotensin-II-receptor blocker for at least 3 months.

- Albuminuria should be treated with an angiotensin-converting enzyme inhibitor (ACE-I)

or angiotensin-II-receptor blocker (ARB) for at least 3 months. Exclusion Criteria:

- Current/chronic use of the following medication: thiazolidinediones, sulfonylurea

derivatives, GLP-1 receptor agonists, dipeptidyl peptidase (DPP)-4 inhibitors, glucocorticoids, immune suppressants, antimicrobial agents, chemotherapeutics, antipsychotics, tricyclic antidepressants and monoamine oxidase inhibitors. 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 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: acute coronary

syndrome, chronic heart failure (New York Heart Association grade II-IV), stroke or transient ischemic neurologic disorder

- 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/alanine aminotransferase) at screening

- History of or actual pancreatic disease

- 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

Locations and Contacts

VU Universtiy Medical Center, Amsterdam 1081 HV, Netherlands; Recruiting
Lennart Tonneijck, MD, Phone: +31-(0)20-4440651, Email: l.tonneijck@vumc.nl
Mark H.H. Kramer, MD PhD, Principal Investigator
Additional Information

Starting date: September 2014
Last updated: February 13, 2015

Page last updated: August 23, 2015

-- advertisement -- The American Red Cross
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017