Effect of LIXIsenatide on the Renal System

Diabetes Mellitus Clinical Trial

— ELIXIRS  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02276196
• Other study ID #: DC2014ELIX001
• Status: Completed
• Phase: Phase 4
• First received: October 16, 2014
• Last updated: April 28, 2016
• Start date: September 2014
• Est. completion date: April 2016

Study information

• Verified date: February 2016
• Source: VU University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: April 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 35 Years to 75 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetic Kidney Disease
• Diabetic Nephropathies
• Diabetic Nephropathy
• Glucagon-Like Peptide 1
• Kidney Diseases

Intervention

Drug:
• Lixisenatide
GLP-1 receptor agonist
• Insulin glulisine
Insulin analogue

Locations

Country	Name	City	State
Netherlands	VU Universtiy Medical Center	Amsterdam

Sponsors (1)

Lead Sponsor	Collaborator
VU University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Body anthropometrics: body weight, height, body mass index, waist circumference	kilogram, meters, centimeters	8 weeks	No
Other	Body fat content	e.g. percentage (%)	8 weeks	No
Other	Glycemic variables	e.g. mmol/l, mmol/mol	8 weeks	No
Other	Lipid spectrum	e.g. mmol/l	8 weeks	No
Other	Inflammatory markers	e.g. nmol/l	8 weeks	Yes
Other	Systemic hemodynamic variables	e.g. ml/min	8 weeks	No
Other	Heart rate	beat per minute	8 weeks	No
Other	Microvascular function	e.g. count	8 weeks	No
Other	Arterial stiffness	e.g. augmentation index	8 weeks	No
Primary	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)	ml/min	8 weeks	No
Secondary	Renal damage, measured by urine biomarkers	enzyme immuno assay	8 weeks	No
Secondary	Renal tubular function	e.g. percentage (%)	8 weeks	No
Secondary	Blood Pressure	mmHg	8 weeks	No