The Effect of Liraglutide in Patients With Prediabetes and Kidney Failure

Kidney Failure, Chronic Clinical Trial

— LiRA2  

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02284230
• Other study ID #: U1111-1149-7801
• Status: Withdrawn
• Phase: Phase 2
• First received: November 3, 2014
• Last updated: August 21, 2015
• Start date: December 2014
• Est. completion date: August 2015

Study information

• Verified date: August 2015
• Source: Rigshospitalet, Denmark
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Dataprotection AgencyDenmark: The National Committee on Health Research EthicsDenmark: Danish Health and Medicines Authority
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: August 2015
• Est. primary completion date: August 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Kidney Failure, Chronic
• Prediabetic State
• Renal Insufficiency

Intervention

Drug:
• Liraglutide

• Placebo

Locations

Country	Name	City	State
Denmark	Department of Nephrology, Rigshospitalet	Copenhagen

Sponsors (3)

Lead Sponsor	Collaborator
Bo Feldt-Rasmussen	Novo Nordisk A/S, The GCP unit at Copenhagen University Hospital

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	The trial visit of week 26	No
Secondary	Hypoglycemic incidents	Total hypoglycemic episodes during intervention	From the randomisation to trial visit of week 26	Yes
Secondary	Fasting values of glucometabolic hormones	Fasting plasma glucose, proinsulin, insulin and glucagon	The trial visit of week 26	No
Secondary	Insulin resistance	Insulin resistance evaluated by homeostasis model assessment (HOMA)	The trial visit of week 26	No
Secondary	Beta cell function	Beta-cell function evaluated by HOMA	The trial visit of week 26	No
Secondary	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))	The trial visit of week 26	No
Secondary	Blood pressure	Blood Pressure	The trial visit of week 26	No
Secondary	Pulse	Resting pulse	The trial visit of week 26	No
Secondary	Weight	Weight	The trial visit of week 26	No
Secondary	Body composition	Body composition by dual energy x-ray absorptiometry (DXA) scan	The trial visit of week 26	No
Secondary	Cardiac function and perfusion	Cardiac function and perfusion evaluated by Rb-PET/CT scan	The trial visit of week 26	No
Secondary	Cardiac autonomic function	Cardiac autonomic function evaluated by heart rate variability	The trial visit of week 26	No
Secondary	Arterial stiffness	Arterial stiffness evaluated by Augmentation index from Pulse wave analysis	The trial visit of week 26	No
Secondary	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)	The trial visit of week 26	No
Secondary	Prothrombotic state	Prothrombotic state (fibrinogen, activated partial thromboplastin time (APTT) and thromboelastography (TEG))	The trial visit of week 26	No
Secondary	Lipid profile	Lipid profile	The trial visit of week 26	No
Secondary	Plasma liraglutide	Plasma liraglutide	The trial visit of week 26	No