Effect of LIXIsenatide on the Renal System - Full Text View

Purpose

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.

Condition	Intervention	Phase
Diabetic Kidney Disease Diabetic Nephropathy Diabetes Mellitus Glucagon-Like Peptide 1	Drug: Lixisenatide Drug: Insulin glulisine	Phase 4


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
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

Resource links provided by NLM:

Drug Information available for: Insulin Insulin human Insulin glulisine Lixisenatide

U.S. FDA Resources

Further study details as provided by M.H.H. Kramer, VU University Medical Center:

Primary Outcome Measures:

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) [ Time Frame: 8 weeks ]
ml/min

Secondary Outcome Measures:

Renal damage, measured by urine biomarkers [ Time Frame: 8 weeks ]
enzyme immuno assay
Renal tubular function [ Time Frame: 8 weeks ]
e.g. percentage (%)
Blood Pressure [ Time Frame: 8 weeks ]
mmHg

Other Outcome Measures:

Body anthropometrics: body weight, height, body mass index, waist circumference [ Time Frame: 8 weeks ]
kilogram, meters, centimeters
Body fat content [ Time Frame: 8 weeks ]
e.g. percentage (%)
Glycemic variables [ Time Frame: 8 weeks ]
e.g. mmol/l, mmol/mol
Lipid spectrum [ Time Frame: 8 weeks ]
e.g. mmol/l
Inflammatory markers [ Time Frame: 8 weeks ]
e.g. nmol/l
Systemic hemodynamic variables [ Time Frame: 8 weeks ]
e.g. ml/min
Heart rate [ Time Frame: 8 weeks ]
beat per minute
Microvascular function [ Time Frame: 8 weeks ]
e.g. count
Arterial stiffness [ Time Frame: 8 weeks ]
e.g. augmentation index


Enrollment:	40
Study Start Date:	September 2014
Study Completion Date:	April 2016
Primary Completion Date:	April 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Lixisenatide Lixisenatide will be administered subcutaneously, once daily for 8 weeks	Drug: Lixisenatide GLP-1 receptor agonist Other Name: Lyxumia
Active Comparator: Insulin glulisine Insulin glulisine will be administered subcutaneously, once daily for 8 weeks	Drug: Insulin glulisine Insulin analogue Other Name: Apidra

Eligibility


Ages Eligible for Study:	35 Years to 75 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02276196

Locations


Netherlands
VU Universtiy Medical Center
Amsterdam, Netherlands, 1081 HV

Sponsors and Collaborators

VU University Medical Center

More Information


Responsible Party:	M.H.H. Kramer, MD PhD, VU University Medical Center
ClinicalTrials.gov Identifier:	NCT02276196 History of Changes
Other Study ID Numbers:	DC2014ELIX001
Study First Received:	October 16, 2014
Last Updated:	April 28, 2016

Additional relevant MeSH terms:


Diabetes Mellitus Kidney Diseases Diabetic Nephropathies Glucose Metabolism Disorders Metabolic Diseases Endocrine System Diseases Urologic Diseases Diabetes Complications Insulin, Globin Zinc	Insulin glulisine Insulin Glucagon-Like Peptide 1 Hypoglycemic Agents Physiological Effects of Drugs Incretins Hormones Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on July 21, 2017

Effect of LIXIsenatide on the Renal System (ELIXIRS)