NCT02276196

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
40

participants targeted

Target at P25-P50 for phase_4

Timeline
Completed

Started Sep 2014

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 1, 2014

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

October 16, 2014

Completed
12 days until next milestone

First Posted

Study publicly available on registry

October 28, 2014

Completed
1.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2016

Completed
Last Updated

April 29, 2016

Status Verified

February 1, 2016

Enrollment Period

1.6 years

First QC Date

October 16, 2014

Last Update Submit

April 28, 2016

Conditions

Diabetic Kidney DiseaseDiabetic NephropathyDiabetes MellitusGlucagon-Like Peptide 1

Outcome Measures

Primary Outcomes (1)

  • 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

Secondary Outcomes (3)

  • Renal damage, measured by urine biomarkers

    8 weeks

  • Renal tubular function

    8 weeks

  • Blood Pressure

    8 weeks

Other Outcomes (9)

  • Body anthropometrics: body weight, height, body mass index, waist circumference

    8 weeks

  • Body fat content

    8 weeks

  • Glycemic variables

    8 weeks

  • +6 more other outcomes

Study Arms (2)

Lixisenatide

EXPERIMENTAL

Lixisenatide will be administered subcutaneously, once daily for 8 weeks

Drug: Lixisenatide

Insulin glulisine

ACTIVE COMPARATOR

Insulin glulisine will be administered subcutaneously, once daily for 8 weeks

Drug: Insulin glulisine

Interventions

LixisenatideDRUG

GLP-1 receptor agonist

Also known as: Lyxumia
Lixisenatide
Insulin glulisineDRUG

Insulin analogue

Also known as: Apidra
Insulin glulisine

Eligibility Criteria

Age35 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

VU Universtiy Medical Center

Amsterdam, 1081 HV, Netherlands

Location

Related Publications (1)

  • 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.

    PMID: 28449402DERIVED

MeSH Terms

Conditions

Diabetic NephropathiesDiabetes Mellitus

Interventions

lixisenatideinsulin glulisine

Condition Hierarchy (Ancestors)

Kidney DiseasesUrologic DiseasesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital DiseasesDiabetes ComplicationsEndocrine System DiseasesGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic Diseases

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD PhD

Study Record Dates

First Submitted

October 16, 2014

First Posted

October 28, 2014

Study Start

September 1, 2014

Primary Completion

April 1, 2016

Study Completion

April 1, 2016

Last Updated

April 29, 2016

Record last verified: 2016-02

Locations

NL(1)