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Liraglutide Treatment to Patients With Severe Renal Insufficiency

This study has been completed.
Sponsor:
Collaborators:
Novo Nordisk A/S
The GCP unit at Copenhagen University Hospital
Information provided by (Responsible Party):
Bo Feldt-Rasmussen, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier:
NCT01394341
First received: July 11, 2011
Last updated: October 8, 2013
Last verified: October 2013
  Purpose

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


Condition Intervention Phase
Type 2 Diabetes Mellitus
End-stage Renal Disease
Drug: Liraglutide
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Safety and Effect of Liraglutide in Patients With Type 2 Diabetes and Severe Renal Insufficiency

Resource links provided by NLM:


Further study details as provided by Rigshospitalet, Denmark:

Primary Outcome Measures:
  • Plasma liraglutide concentration (pmol/L) [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    Plasma liraglutide concentration evaluated over time during continuous intervention


Secondary Outcome Measures:
  • Hypoglycaemia; minor or major [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    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)

  • Glycaemic control [ Time Frame: 12 weeka ] [ Designated as safety issue: No ]
    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.

  • Pancreatic beta-cell function [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Pancreatic beta-cell function evaluated from insulin- and C-peptide-secretion during a standard meal test 3 times during the intervention period.

  • Cardiovascular risk factors (lipids and blood pressure) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Blood pressure will be evaluated at each visit and lipid profile (HDL, LDL, total cholesterol and triglyceride) 3 times during the intervention period.


Enrollment: 40
Study Start Date: September 2011
Study Completion Date: October 2013
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: T2D, Dialysis, Liraglutide
Daily liraglutide treatment Chronic dialysis treatment
Drug: Liraglutide
Daily sc. injection, individual dosage
Other Name: Victoza
Placebo Comparator: T2D, Dialysis, Placebo
Daily placebo Chronic dialysis treatment
Drug: Liraglutide
Daily sc. injection, individual dosage
Other Name: Victoza
Active Comparator: T2D, Normal kidney function, Liraglutide
Daily Liraglutide treatment Normal kidney function
Drug: Liraglutide
Daily sc. injection, individual dosage
Other Name: Victoza
Placebo Comparator: T2D, Normal kidney function, Placebo
Daily placebo treatment Normal kidney function
Drug: Liraglutide
Daily sc. injection, individual dosage
Other Name: Victoza

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01394341

Locations
Denmark
Department of Endocrinology PE, Copenhagen University Hospital, Rigshospitalet
Copenhagen Ø, Copenhagen, Denmark, 2100
Department of Nephrology P, Copenhagen University Hospital, Rigshospitalet
Copenhagen Ø, Copenhagen, Denmark, 2100
Department of Internal Medicine H, Hillerød Hospital
Hillerød, Denmark, 3400
Sponsors and Collaborators
Bo Feldt-Rasmussen
Novo Nordisk A/S
The GCP unit at Copenhagen University Hospital
Investigators
Study Director: Bo Feldt-Rasmussen, Prof, DMSc Department of Nephrology P, Copenhagen University Hospital, Rigshospitalet
Principal Investigator: Thomas Idorn, MD Department of Nephrology P, Copenhagen University Hospital, Rigshospitalet
  More Information

No publications provided

Responsible Party: Bo Feldt-Rasmussen, Professor, DMSc, Head of Department, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier: NCT01394341     History of Changes
Other Study ID Numbers: H-3-2011-032, 2010-021922-36
Study First Received: July 11, 2011
Last Updated: October 8, 2013
Health Authority: Denmark: Danish Dataprotection Agency
Denmark: Danish Medicines Agency
Denmark: The Regional Committee on Biomedical Research Ethics

Keywords provided by Rigshospitalet, Denmark:
Liraglutide
Uremia
Dialysis
Type 2 diabetes mellitus
Safety
Efficacy

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Kidney Diseases
Kidney Failure, Chronic
Renal Insufficiency
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Renal Insufficiency, Chronic
Urologic Diseases
Glucagon-Like Peptide 1
Liraglutide
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Hypoglycemic Agents
Incretins
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 20, 2014