LIraglutide and Beta-cell RepAir (LIBRA) Study - Full Text View

Purpose

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by progressive deterioration in the function of the pancreatic beta-cells, which are the cells that produce and secrete insulin (the hormone primarily responsible for the handling of glucose in the body). We propose a double-blind, randomized controlled study comparing the effect of liraglutide (a novel anti-diabetic drug with beta-cell protective potential) versus placebo, on the preservation of beta-cell function over one year in patients with T2DM. This study may demonstrate an important beta-cell protective capacity of liraglutide.

Condition	Intervention	Phase
Type 2 Diabetes	Drug: Liraglutide Drug: placebo	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Randomized Controlled Study Assessing the Effect of Liraglutide on the Preservation of Beta-Cell Function in Patients With Type 2 Diabetes Mellitus: The LIraglutide and Beta-cell RepAir (LIBRA) Study

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Medicines

Drug Information available for: Liraglutide

U.S. FDA Resources

Further study details as provided by Mount Sinai Hospital, Canada:

Primary Outcome Measures:

Preservation of beta-cell function measured by Insulin Secretion-Sensitivity Index-2 (ISSI-2) [ Time Frame: 48-weeks ] [ Designated as safety issue: No ]
ISSI-2 is a validated OGTT-derived measure of beta-cell function analogous to the disposition index obtained from the intravenous glucose tolerance test. ISSI-2 is defined as the product of (i) insulin secretion measured by the ratio of the area-under-the-insulin-curve (AUCins) to the area-under-the-glucose curve (AUCgluc) and (ii) insulin sensitivity measured by the Matsuda index.

Secondary Outcome Measures:

Glycemic Control [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
- A1c
- Fasting glucose, 2 hour glucose, and AUCgluc on OGTT
- Proportion of participants with A1c <7% at study end
- Glucose tolerance status at study end (NGT, pre-diabetes, diabetes)
- Proportion of participants with fasting glucose in non-diabetic range at study end (ie. <7.0 mmol/L)
- Time to loss of glycemic control


Enrollment:	63
Study Start Date:	January 2011
Study Completion Date:	May 2014
Primary Completion Date:	December 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Liraglutide	Drug: Liraglutide Liraglutide administered as once daily sc injection Other Name: Victoza
Placebo Comparator: Placebo	Drug: placebo placebo administered as once daily sc injection

Detailed Description:

In this study, patients with type 2 diabetes who meet randomization criteria will be randomized to either liraglutide or placebo, with serial assessment of beta-cell function over 48 weeks follow-up. The hypothesis under study is whether liraglutide can preserve beta-cell function.

Eligibility


Ages Eligible for Study:	30 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

men and women between the ages of 30 and 75 years inclusive
physician-diagnosed type 2 diabetes of </= 7 years duration
negative for anti-GAD antibodies
on 0-2 oral anti-diabetic medications
A1c at screening between 5.5% and 9.0% inclusive, if on oral anti-diabetic medications, or between 6.0% and 10.0% inclusive, if not on oral anti-diabetic medications

Exclusion Criteria:

use of insulin, GLP-1 agonist, or dipeptidyl peptidase-4 (DPP-4) inhibitor
type 1 diabetes or secondary forms of diabetes
major illness with life expectancy < 5 years
involvement in another study requiring drug therapy
hypersensitivity to insulin, liraglutide, or metformin
renal dysfunction
hepatic dysfunction
history of pancreatitis
family or personal history of Multiple Endocrine Neoplasia type 2 (MEN-2) or familial medullary thyroid carcinoma
personal history of non-familial medullary thyroid carcinoma
malignant neoplasm requiring chemotherapy, surgery, radiation or palliative therapy within the previous 5 years (with the exception of basal cell skin cancer)
excessive alcohol consumption
unwillingness to undergo multiple daily insulin injection therapy
unwillingness to perform capillary blood glucose monitoring at least 4 times per day during intensive insulin therapy
congestive heart failure
pregnancy

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: NCT01270789

Locations


Canada, Ontario
Mount Sinai Hospital
Toronto, Ontario, Canada, M5G1X5

Sponsors and Collaborators

Mount Sinai Hospital, Canada

Novo Nordisk A/S

Investigators


Principal Investigator:	Ravi Retnakaran, MD	Mount Sinai Hospital, Canada

More Information

No publications provided by Mount Sinai Hospital, Canada

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Retnakaran R, Kramer CK, Choi H, Swaminathan B, Zinman B. Liraglutide and the preservation of pancreatic β-cell function in early type 2 diabetes: the LIBRA trial. Diabetes Care. 2014 Dec;37(12):3270-8. doi: 10.2337/dc14-0893. Epub 2014 Sep 23.

Kramer CK, Choi H, Zinman B, Retnakaran R. Glycemic variability in patients with early type 2 diabetes: the impact of improvement in β-cell function. Diabetes Care. 2014 Apr;37(4):1116-23. doi: 10.2337/dc13-2591. Epub 2014 Feb 18.

Kramer CK, Choi H, Zinman B, Retnakaran R. Determinants of reversibility of β-cell dysfunction in response to short-term intensive insulin therapy in patients with early type 2 diabetes. Am J Physiol Endocrinol Metab. 2013 Dec 1;305(11):E1398-407. doi: 10.1152/ajpendo.00447.2013. Epub 2013 Oct 15.


Responsible Party:	Mount Sinai Hospital, Canada
ClinicalTrials.gov Identifier:	NCT01270789 History of Changes
Other Study ID Numbers:	10-0230-A
Study First Received:	January 4, 2011
Last Updated:	September 10, 2014
Health Authority:	Canada: Health Canada

Keywords provided by Mount Sinai Hospital, Canada:


beta-cell function GLP-1 analogue diabetes

Additional relevant MeSH terms:


Liraglutide Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Hypoglycemic Agents	Incretins Pharmacologic Actions Physiological Effects of Drugs

ClinicalTrials.gov processed this record on March 03, 2015