Liraglutide Treatment to Patients With Severe Renal Insufficiency

Type 2 Diabetes Mellitus Clinical Trial

Official title:

Safety and Effect of Liraglutide in Patients With Type 2 Diabetes and Severe Renal Insufficiency

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01394341
• Other study ID #: H-3-2011-032
• Secondary ID: 2010-021922-36
• Status: Completed
• Phase: Phase 4
• First received: July 11, 2011
• Last updated: October 8, 2013
• Start date: September 2011
• Est. completion date: October 2013

Study information

• Verified date: October 2013
• Source: Rigshospitalet, Denmark
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Dataprotection AgencyDenmark: Danish Medicines AgencyDenmark: The Regional Committee on Biomedical Research Ethics
• Study type: Interventional

Clinical Trial Summary

Incretin-based therapy for the treatment of patients with type 2 diabetes mellitus (T2D) is new and fundamentally different from the classical treatments with oral antidiabetic agents and insulin. The novel and original aspect of this investigator-initiated study is the focus on treatment with an incretin-based agent (the GLP-1 analogue liraglutide) in T2D patients with severely reduced kidney function. At present there is virtually no knowledge of the physiology and clinical implications of the role of incretin hormones and incretin-based therapy in this group of diabetic patients.The aim of the study is to establish an evidence-based rationale for introducing a GLP-1 analogue to the limited armamentarium of antidiabetic drugs for patients with type T2D and severe renal insufficiency. The overall hypothesis is that patients with T2D and severe renal insufficiency will tolerate and benefit from treatment with the GLP-1 analogue liraglutide, hereby improving glycaemic control and reducing risk factors of cardiovascular disease

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: October 2013
• Est. primary completion date: October 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

Inclusion criteria - patients with T2D in dialysis

• Male or female; aged 18-85 years

• End-stage renal disease

• Chronic dialysis treatment (minimum 3 months)

• T2D (diagnosed according to WHO criteria)

• Treated with diet/lifestyle intervention, oral antidiabetic drugs (SU, glitazones) and/or insulin

• Documented beta cell function (evaluated by a glucagon test)

Inclusion criteria - patients with T2D and normal kidney function

• Male or female; aged 18-85 years

• Normal kidney function: Plasma creatinine <0.105 mmol/L for men and <0.090 mmol/L for women

• T2D (diagnosed according to WHO criteria)

• Treated with diet/lifestyle intervention, oral antidiabetic drugs (SU, glitazones) and/or insulin

• Documented beta cell function (evaluated by a glucagon test)

• Hemoglobin A1c =6.5%

Exclusion Criteria - both groups

• Type 1 diabetes mellitus

• Chronic pancreatitis / previous acute pancreatitis

• Known or suspected hypersensitivity to trial product(s) or related products

• Treatment with oral glucocorticoids, calcineurin inhibitors, dipeptidyl peptidase 4 (DPP4) inhibitors or other drugs, 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 investigators' opinion could interfere with the results of the trial

• Inflammatory bowel disease

• 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 = 18.5 kg/m2 or = 50.0 kg/m2

• Females of childbearing potential who are pregnant, breast-feeding, intend to become pregnant or are not using adequate contraceptive methods

• Clinical signs of diabetic gastroparesis

• Impaired liver function (transaminases >two times upper reference levels)

• 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

Study Design

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• End-stage Renal Disease
• Kidney Failure, Chronic
• Renal Insufficiency
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Liraglutide
Daily sc. injection, individual dosage

Locations

Country	Name	City	State
Denmark	Department of Endocrinology PE, Copenhagen University Hospital, Rigshospitalet	Copenhagen Ø	Copenhagen
Denmark	Department of Nephrology P, Copenhagen University Hospital, Rigshospitalet	Copenhagen Ø	Copenhagen
Denmark	Department of Internal Medicine H, Hillerød Hospital	Hillerød

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 liraglutide concentration (pmol/L)	Plasma liraglutide concentration evaluated over time during continuous intervention	12 weeks	Yes
Secondary	Hypoglycaemia; minor or major	Number of hypoglycaemic episodes during intervention. Minor (blood glucose <3.1 mmol/L, no need for assistance). Major (blood glucose <3.1 mmol/L, assistance from third person required)	12 weeks	Yes
Secondary	Glycaemic control	Glycaemic control evaluated from 3 daily measurements of blood glucose, from 4 periods of 24-hour tissue glucose measurements (5 days each) and from HbA1c during the intervention period.	12 weeka	No
Secondary	Pancreatic beta-cell function	Pancreatic beta-cell function evaluated from insulin- and C-peptide-secretion during a standard meal test 3 times during the intervention period.	12 weeks	No
Secondary	Cardiovascular risk factors (lipids and blood pressure)	Blood pressure will be evaluated at each visit and lipid profile (HDL, LDL, total cholesterol and triglyceride) 3 times during the intervention period.	12 weeks	No