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Effect of LIXIsenatide on the Renal System (ELIXIRS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02276196
Recruitment Status : Completed
First Posted : October 28, 2014
Last Update Posted : April 29, 2016
Sponsor:
Information provided by (Responsible Party):
M.H.H. Kramer, Amsterdam UMC, location VUmc

Tracking Information
First Submitted Date  ICMJE October 16, 2014
First Posted Date  ICMJE October 28, 2014
Last Update Posted Date April 29, 2016
Study Start Date  ICMJE September 2014
Actual Primary Completion Date April 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 27, 2014)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 27, 2014)
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: October 27, 2014)
  • 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
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Effect of LIXIsenatide on the Renal System
Official Title  ICMJE 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
Brief 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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Diabetic Kidney Disease
  • Diabetic Nephropathy
  • Diabetes Mellitus
  • Glucagon-Like Peptide 1
Intervention  ICMJE
  • Drug: Lixisenatide
    GLP-1 receptor agonist
    Other Name: Lyxumia
  • Drug: Insulin glulisine
    Insulin analogue
    Other Name: Apidra
Study Arms  ICMJE
  • Experimental: Lixisenatide
    Lixisenatide will be administered subcutaneously, once daily for 8 weeks
    Intervention: Drug: Lixisenatide
  • Active Comparator: Insulin glulisine
    Insulin glulisine will be administered subcutaneously, once daily for 8 weeks
    Intervention: Drug: Insulin glulisine
Publications * Tonneijck L, Muskiet MHA, Smits MM, Hoekstra T, Kramer MHH, Danser AHJ, Diamant M, Joles JA, van Raalte DH. Postprandial renal haemodynamic effect of lixisenatide vs once-daily insulin-glulisine in patients with type 2 diabetes on insulin-glargine: An 8-week, randomised, open-label trial. Diabetes Obes Metab. 2017 Dec;19(12):1669-1680. doi: 10.1111/dom.12985. Epub 2017 Jul 25.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 27, 2014)
40
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE April 2016
Actual Primary Completion Date April 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 35 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02276196
Other Study ID Numbers  ICMJE DC2014ELIX001
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party M.H.H. Kramer, Amsterdam UMC, location VUmc
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Amsterdam UMC, location VUmc
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Amsterdam UMC, location VUmc
Verification Date February 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP