LIraglutide and Beta-cell RepAir (LIBRA) Study

NCT01270789 | Completed Phase 3

• 1 other identifier: 10-0230-A
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Type 2 Diabetes

Keywords

beta-cell function; GLP-1 analogue; diabetes

Outcome Measures

Primary Outcomes (1)

• Preservation of beta-cell function measured by Insulin Secretion-Sensitivity Index-2 (ISSI-2)

  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.

  48-weeks

Secondary Outcomes (1)

• Glycemic Control

  48 weeks

Study Arms (2)

Liraglutide

EXPERIMENTAL

Drug: Liraglutide

Placebo

PLACEBO COMPARATOR

Drug: placebo

Interventions

Liraglutide DRUG

Liraglutide administered as once daily sc injection

Also known as: Victoza

Liraglutide

placebo DRUG

placebo administered as once daily sc injection

Placebo

Eligibility Criteria

• Age: 30 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mount Sinai Hospital, Canada: lead
• Novo Nordisk A/S: collaborator

Study Sites (1)

Mount Sinai Hospital

Toronto, Ontario, M5G1X5, Canada

Location

Related Publications (9)

• Nunez Lopez YO, Retnakaran R, Zinman B, Pratley RE, Seyhan AA. Predicting and understanding the response to short-term intensive insulin therapy in people with early type 2 diabetes. Mol Metab. 2019 Feb;20:63-78. doi: 10.1016/j.molmet.2018.11.003. Epub 2018 Nov 16.

  PMID: 30503831 DERIVED

• Kramer CK, Zinman B, Choi H, Connelly PW, Retnakaran R. Impact of the Glucagon Assay When Assessing the Effect of Chronic Liraglutide Therapy on Glucagon Secretion. J Clin Endocrinol Metab. 2017 Aug 1;102(8):2729-2733. doi: 10.1210/jc.2017-00928.

  PMID: 28472325 DERIVED

• Kramer CK, Zinman B, Choi H, Retnakaran R. Predictors of sustained drug-free diabetes remission over 48 weeks following short-term intensive insulin therapy in early type 2 diabetes. BMJ Open Diabetes Res Care. 2016 Aug 1;4(1):e000270. doi: 10.1136/bmjdrc-2016-000270. eCollection 2016.

  PMID: 27547422 DERIVED

• Kramer CK, Zinman B, Choi H, Connelly PW, Retnakaran R. The Impact of Chronic Liraglutide Therapy on Glucagon Secretion in Type 2 Diabetes: Insight From the LIBRA Trial. J Clin Endocrinol Metab. 2015 Oct;100(10):3702-9. doi: 10.1210/jc.2015-2725. Epub 2015 Jul 31.

  PMID: 26230296 DERIVED

• Kramer CK, Zinman B, Choi H, Retnakaran R. Effect of Short-term Intensive Insulin Therapy on Post-challenge Hyperglucagonemia in Early Type 2 Diabetes. J Clin Endocrinol Metab. 2015 Aug;100(8):2987-95. doi: 10.1210/jc.2015-1947. Epub 2015 Jun 16.

  PMID: 26079776 DERIVED

• Stein CM, Kramer CK, Zinman B, Choi H, Opsteen C, Retnakaran R. Clinical predictors and time course of the improvement in beta-cell function with short-term intensive insulin therapy in patients with Type 2 diabetes. Diabet Med. 2015 May;32(5):645-52. doi: 10.1111/dme.12671. Epub 2015 Jan 7.

  PMID: 25495067 DERIVED

• Retnakaran R, Kramer CK, Choi H, Swaminathan B, Zinman B. Liraglutide and the preservation of pancreatic beta-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.

  PMID: 25249651 DERIVED

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

  PMID: 24550219 DERIVED

• Kramer CK, Choi H, Zinman B, Retnakaran R. Determinants of reversibility of beta-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.

  PMID: 24129396 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetes Mellitus

Interventions

Liraglutide

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Ravi Retnakaran, MD

  Mount Sinai Hospital, Canada

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2011
• First Posted: January 5, 2011
• Study Start: January 1, 2011
• Primary Completion: December 1, 2013
• Study Completion: May 1, 2014
• Last Updated: September 12, 2014

Record last verified: 2014-09

Locations

CA (1)