Clinical trial NCT01394341: Liraglutide Treatment to Patients With Severe Renal Insufficiency
Official title: Safety and Effect of Liraglutide in Patients With Type 2 Diabetes and Severe Renal Insufficiency
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 2 Diabetes Mellitus
End-stage Renal Disease
Keywords: Liraglutide
Uremia
Dialysis
Type 2 diabetes mellitus
Safety
Efficacy
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: Novo Nordisk A/S
name: The GCP unit at Copenhagen University Hospital
First posted: 2011-07-14
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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


Eligibility criteria: 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

Primary outcomes:
measure: Plasma liraglutide concentration (pmol/L)
timeFrame: 12 weeks
Secondary outcomes:
measure: Hypoglycaemia; minor or major
timeFrame: 12 weeks
measure: Glycaemic control
timeFrame: 12 weeka
measure: Pancreatic beta-cell function
timeFrame: 12 weeks
measure: Cardiovascular risk factors (lipids and blood pressure)
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Copenhagen Ø
country: Denmark
facility: Department of Endocrinology PE, Copenhagen University Hospital, Rigshospitalet
state: Copenhagen
city: Copenhagen Ø
country: Denmark
facility: Department of Nephrology P, Copenhagen University Hospital, Rigshospitalet
state: Copenhagen
city: Hillerød
country: Denmark
facility: Department of Internal Medicine H, Hillerød Hospital
Study officials:
affiliation: Department of Nephrology P, Copenhagen University Hospital, Rigshospitalet
name: Bo Feldt-Rasmussen, Prof, DMSc
role: STUDY_DIRECTOR
affiliation: Department of Nephrology P, Copenhagen University Hospital, Rigshospitalet
name: Thomas Idorn, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Idorn T, Knop FK, Jorgensen MB, Jensen T, Resuli M, Hansen PM, Christensen KB, Holst JJ, Hornum M, Feldt-Rasmussen B. Safety and Efficacy of Liraglutide in Patients With Type 2 Diabetes and End-Stage Renal Disease: An Investigator-Initiated, Placebo-Controlled, Double-Blind, Parallel-Group, Randomized Trial. Diabetes Care. 2016 Feb;39(2):206-13. doi: 10.2337/dc15-1025. Epub 2015 Aug 17.
citation: Idorn T, Knop FK, Jorgensen M, Jensen T, Resuli M, Hansen PM, Christensen KB, Holst JJ, Hornum M, Feldt-Rasmussen B. Safety and efficacy of liraglutide in patients with type 2 diabetes and end-stage renal disease: protocol for an investigator-initiated prospective, randomised, placebo-controlled, double-blinded, parallel intervention study. BMJ Open. 2013 Apr 26;3(4):e002764. doi: 10.1136/bmjopen-2013-002764. Print 2013.