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

Primary Purpose

Kidney Failure, Chronic, Prediabetic State

Status
Withdrawn
Phase
Phase 2
Locations
Denmark
Study Type
Interventional
Intervention
Liraglutide
Placebo
Sponsored by
Bo Feldt-Rasmussen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Kidney Failure, Chronic

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Department of Nephrology, Rigshospitalet

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Liraglutide treatment

Placebo treatment

Arm Description

Subcutaneous, once daily injection of liraglutide, individually dosed up to 1.8 mg/day.

Subcutaneous, once daily injection of placebo, individually dosed up to 1.8 mg/day.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Hypoglycemic incidents
Total hypoglycemic episodes during intervention
Fasting values of glucometabolic hormones
Fasting plasma glucose, proinsulin, insulin and glucagon
Insulin resistance
Insulin resistance evaluated by homeostasis model assessment (HOMA)
Beta cell function
Beta-cell function evaluated by HOMA
Change in glycemic state
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))
Blood pressure
Blood Pressure
Pulse
Resting pulse
Weight
Weight
Body composition
Body composition by dual energy x-ray absorptiometry (DXA) scan
Cardiac function and perfusion
Cardiac function and perfusion evaluated by Rb-PET/CT scan
Cardiac autonomic function
Cardiac autonomic function evaluated by heart rate variability
Arterial stiffness
Arterial stiffness evaluated by Augmentation index from Pulse wave analysis
Cardiovascular and endothelial risk markers
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)
Prothrombotic state
Prothrombotic state (fibrinogen, activated partial thromboplastin time (APTT) and thromboelastography (TEG))
Lipid profile
Lipid profile
Plasma liraglutide
Plasma liraglutide

Full Information

First Posted
November 3, 2014
Last Updated
August 21, 2015
Sponsor
Bo Feldt-Rasmussen
Collaborators
Novo Nordisk A/S, The GCP unit at Copenhagen University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT02284230
Brief Title
The Effect of Liraglutide in Patients With Prediabetes and Kidney Failure
Acronym
LiRA2
Official Title
Glycaemic and Cardiovascular Efficacy of Liraglutide in Prediabetic Patients With End-stage Renal Disease
Study Type
Interventional

2. Study Status

Record Verification Date
August 2015
Overall Recruitment Status
Withdrawn
Why Stopped
Inability to recruit participants
Study Start Date
December 2014 (undefined)
Primary Completion Date
August 2015 (Actual)
Study Completion Date
August 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Bo Feldt-Rasmussen
Collaborators
Novo Nordisk A/S, The GCP unit at Copenhagen University Hospital

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Kidney Failure, Chronic, Prediabetic State

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Liraglutide treatment
Arm Type
Active Comparator
Arm Description
Subcutaneous, once daily injection of liraglutide, individually dosed up to 1.8 mg/day.
Arm Title
Placebo treatment
Arm Type
Placebo Comparator
Arm Description
Subcutaneous, once daily injection of placebo, individually dosed up to 1.8 mg/day.
Intervention Type
Drug
Intervention Name(s)
Liraglutide
Other Intervention Name(s)
Victoza
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Plasma glucose during oral glucose tolerance test at week 26
Description
Difference between the two treatment arms in plasma glucose concentrations during a 3h 75g-OGTT on the trial visit of week 26
Time Frame
The trial visit of week 26
Secondary Outcome Measure Information:
Title
Hypoglycemic incidents
Description
Total hypoglycemic episodes during intervention
Time Frame
From the randomisation to trial visit of week 26
Title
Fasting values of glucometabolic hormones
Description
Fasting plasma glucose, proinsulin, insulin and glucagon
Time Frame
The trial visit of week 26
Title
Insulin resistance
Description
Insulin resistance evaluated by homeostasis model assessment (HOMA)
Time Frame
The trial visit of week 26
Title
Beta cell function
Description
Beta-cell function evaluated by HOMA
Time Frame
The trial visit of week 26
Title
Change in glycemic state
Description
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))
Time Frame
The trial visit of week 26
Title
Blood pressure
Description
Blood Pressure
Time Frame
The trial visit of week 26
Title
Pulse
Description
Resting pulse
Time Frame
The trial visit of week 26
Title
Weight
Description
Weight
Time Frame
The trial visit of week 26
Title
Body composition
Description
Body composition by dual energy x-ray absorptiometry (DXA) scan
Time Frame
The trial visit of week 26
Title
Cardiac function and perfusion
Description
Cardiac function and perfusion evaluated by Rb-PET/CT scan
Time Frame
The trial visit of week 26
Title
Cardiac autonomic function
Description
Cardiac autonomic function evaluated by heart rate variability
Time Frame
The trial visit of week 26
Title
Arterial stiffness
Description
Arterial stiffness evaluated by Augmentation index from Pulse wave analysis
Time Frame
The trial visit of week 26
Title
Cardiovascular and endothelial risk markers
Description
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)
Time Frame
The trial visit of week 26
Title
Prothrombotic state
Description
Prothrombotic state (fibrinogen, activated partial thromboplastin time (APTT) and thromboelastography (TEG))
Time Frame
The trial visit of week 26
Title
Lipid profile
Description
Lipid profile
Time Frame
The trial visit of week 26
Title
Plasma liraglutide
Description
Plasma liraglutide
Time Frame
The trial visit of week 26

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bo Feldt-Rasmussen, Prof,MD,DMSc
Organizational Affiliation
Rigshospitalet, Denmark
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Nephrology, Rigshospitalet
City
Copenhagen
ZIP/Postal Code
2100
Country
Denmark

12. IPD Sharing Statement

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The Effect of Liraglutide in Patients With Prediabetes and Kidney Failure

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