The Effect of Liraglutide in Patients With Prediabetes and Kidney Failure (LiRA2)

August 21, 2015 updated by: Bo Feldt-Rasmussen

Glycaemic and Cardiovascular Efficacy of Liraglutide in Prediabetic Patients With End-stage Renal Disease

The present study will examine the effects of liraglutide treatment during 26 weeks on several cardiovascular risk factors in patients with prediabetes and end-stage renal disease (ESRD). The primary objective is to determine the efficacy of the treatment on glucose tolerance evaluated during a 3h 75g-oral glucose tolerance test (OGTT). Secondary objectives include various clinical and biochemical cardiovascular and safety parameters.

We hypothesise that treatment with liraglutide can improve glucose tolerance in prediabetic patients with ESRD by normalizing plasma glucose excursions during an OGTT and ameliorate other cardiovascular risk factors.

Study Overview

Status

Withdrawn

Intervention / Treatment

Study Type

Interventional

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Copenhagen, Denmark, 2100
        • Department of Nephrology, Rigshospitalet

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • End-stage renal disease treated with chronic maintenance dialysis (haemodialysis or peritoneal dialysis)
  • Impaired glucose tolerance (2h plasma glucose ≥ 7,8 and < 11.1 mmol/l following a 75g-OGTT) and/or impaired fasting glucose (fasting plasma glucose ≥ 6.1 and < 7.0 mmol/l) evaluated at the screening visit

Exclusion Criteria:

  • Diabetes mellitus type 1 or type 2 (diagnose according to WHO criteria)
  • Chronic pancreatitis / previous acute pancreatitis
  • Known or suspected hypersensitivity to trial product(s) or related products
  • Treatment with oral glucocorticoids, calcineurin inhibitors or incretin-based therapy which in the Investigator's opinion could interfere with glucose or lipid metabolism 90 days prior to screening
  • Cancer (except basal cell skin cancer or squamous cell skin cancer) or any other clinically significant disorder, which in the investigator's opinion could interfere with the results of the trial
  • Clinical suspicion of cardiac disease currently investigated
  • Cardiac disease defined as: decompensated heart failure (NYHA class III-IV) and/or diagnosis of unstable angina pectoris and/or myocardial infarction within the last 6 months
  • Body mass index (BMI) <20 kg/m2 and/or >50 kg/m2
  • Females of childbearing potential who are pregnant, breast-feeding, intend to become pregnant or are not using adequate contraceptive methods*
  • Impaired liver function (transaminases > two times upper reference levels)
  • The receipt of any investigational product 90 days prior to this trial
  • Known or suspected abuse of alcohol or narcotics
  • Screening calcitonin ≥ 50 ng/l
  • Subjects with personal or family history of medullary thyroid carcinoma or a personal history of multiple endocrine neoplasia type 2

Lawfully detained, institutionalised and patients who are unable to give informed consent due to physical or mental conditions will not be included.

* Intrauterine devices and hormonal contraceptives (oral pills, patches, implants, vaginal rings, and injections) are considered as adequate contraceptives. Females of childbearing potential must use one of these contraceptives throughout the entire study plus 1 week after last injection with study medication. Surgical sterile (by bilateral vasectomy, tubectomy, hysterectomy or oophorectomy) or postmenopausal (defined as amenorrheic for at least one year) female participants are not considered as having a childbearing potential and are not required to use contraception.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Liraglutide treatment
Subcutaneous, once daily injection of liraglutide, individually dosed up to 1.8 mg/day.
Other Names:
  • Victoza
Placebo Comparator: Placebo treatment
Subcutaneous, once daily injection of placebo, individually dosed up to 1.8 mg/day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Plasma glucose during oral glucose tolerance test at week 26
Time Frame: The trial visit of week 26
Difference between the two treatment arms in plasma glucose concentrations during a 3h 75g-OGTT on the trial visit of week 26
The trial visit of week 26

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hypoglycemic incidents
Time Frame: From the randomisation to trial visit of week 26
Total hypoglycemic episodes during intervention
From the randomisation to trial visit of week 26
Fasting values of glucometabolic hormones
Time Frame: The trial visit of week 26
Fasting plasma glucose, proinsulin, insulin and glucagon
The trial visit of week 26
Insulin resistance
Time Frame: The trial visit of week 26
Insulin resistance evaluated by homeostasis model assessment (HOMA)
The trial visit of week 26
Beta cell function
Time Frame: The trial visit of week 26
Beta-cell function evaluated by HOMA
The trial visit of week 26
Change in glycemic state
Time Frame: The trial visit of week 26
Change in glycemic state following oral glucose tolerance test (normal glucose tolerance (NGT, fasting plasma glucose < 6.1 mmol/l and 2h plasma glucose < 7.8 mmol/l), impaired fasting glucose (IFG, fasting plasma glucose ≥ 6.1 and < 7.0 mmol/l), impaired glucose tolerance (IGT, 2h plasma glucose ≥ 7,8 and < 11.1 mmol/l) and diabetes mellitus (DM, fasting plasma glucose ≥ 7 mmol/l or 2h plasma glucose ≥ 11.1 mmol/l))
The trial visit of week 26
Blood pressure
Time Frame: The trial visit of week 26
Blood Pressure
The trial visit of week 26
Pulse
Time Frame: The trial visit of week 26
Resting pulse
The trial visit of week 26
Weight
Time Frame: The trial visit of week 26
Weight
The trial visit of week 26
Body composition
Time Frame: The trial visit of week 26
Body composition by dual energy x-ray absorptiometry (DXA) scan
The trial visit of week 26
Cardiac function and perfusion
Time Frame: The trial visit of week 26
Cardiac function and perfusion evaluated by Rb-PET/CT scan
The trial visit of week 26
Cardiac autonomic function
Time Frame: The trial visit of week 26
Cardiac autonomic function evaluated by heart rate variability
The trial visit of week 26
Arterial stiffness
Time Frame: The trial visit of week 26
Arterial stiffness evaluated by Augmentation index from Pulse wave analysis
The trial visit of week 26
Cardiovascular and endothelial risk markers
Time Frame: The trial visit of week 26
Cardiovascular and endothelial risk markers (troponin T, troponin I, creatine kinase-MB, high-sensitivity C-reactive protein (hsCRP), plasminogen activator inhibitor 1 (PAI-1), Tissue plasminogen activator (tPA), urat, von Willebrand factor (vWF), vascular endothelial cell adhesion molecule (VCAM), intercellular adhesion molecule (ICAM), TNFalpha, proBNP, E-selectin and asymmetric dimethylarginine)
The trial visit of week 26
Prothrombotic state
Time Frame: The trial visit of week 26
Prothrombotic state (fibrinogen, activated partial thromboplastin time (APTT) and thromboelastography (TEG))
The trial visit of week 26
Lipid profile
Time Frame: The trial visit of week 26
Lipid profile
The trial visit of week 26
Plasma liraglutide
Time Frame: The trial visit of week 26
Plasma liraglutide
The trial visit of week 26

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Bo Feldt-Rasmussen, Prof,MD,DMSc, Rigshospitalet, Denmark

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2014

Primary Completion (Actual)

August 1, 2015

Study Completion (Actual)

August 1, 2015

Study Registration Dates

First Submitted

November 3, 2014

First Submitted That Met QC Criteria

November 3, 2014

First Posted (Estimate)

November 5, 2014

Study Record Updates

Last Update Posted (Estimate)

August 24, 2015

Last Update Submitted That Met QC Criteria

August 21, 2015

Last Verified

August 1, 2015

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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