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Effect of Liraglutide on Vascular Inflammation in Type-2 Diabetes (LIRAFLAME)

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ClinicalTrials.gov Identifier: NCT03449654
Recruitment Status : Recruiting
First Posted : February 28, 2018
Last Update Posted : February 28, 2018
Sponsor:
Collaborator:
Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet & Cluster for Molecular Imaging, University of Copenhagen, Denmark
Information provided by (Responsible Party):
Peter Rossing, Steno Diabetes Center

Brief Summary:

The objective of this study is to evaluate the mechanism behind the anti-atherogenic effects of liraglutide.

In a randomized, placebo-controlled, double-blind, parallel trial we will included 100 patients with type 2 diabetes. Patients will be randomized 1:1 to an active treatment period of 26 weeks or placebo for 26 weeks.

The primary endpoint is change from baseline to week 26 in vascular inflammation, assessed by Flour Deoxy Glucose (FDG)-Positron Emission Tomography/Computed Tomography (PET/CT)


Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 2 Drug: Liraglutide Drug: Placebo (for liraglutide) Phase 4

Detailed Description:

Despite multifactorial treatment patients with type 2 diabetes are still at high risk of cardiovascular disease. The clinical LEADER trial demonstrated a reduction in cardiovascular events in patients with type 2 diabetes treated with the GLP-1 receptor agonist liraglutide and there are a number of studies indicating that liraglutide has a positive effect on the vascular phenotype. Several of the animal or ex vivo studies suggest an anti-inflammatory mechanism behind this effect. However, no in vivo human studies have been undertaken to test this hypothesis and it would be of significance to determine the precise mechanism since atherosclerosis has large prognostic impact in patients with type 2 diabetes.

The objective of this study is to evaluate the mechanism behind the anti-atherogenic effects of liraglutide.

In a randomized, placebo-controlled, double-blind, parallel trial we will included 100 patients with type 2 diabetes. Patients will be randomized 1:1 to an active treatment period of 26 weeks or placebo for 26 weeks.

The primary endpoint is change from baseline to week 26 in vascular inflammation, assessed by Flour Deoxy Glucose (FDG)-Positron Emission Tomography/Computed Tomography (PET/CT). FDG-PET/CT is currently the only clinically available technique for specific in vivo evaluation of vascular inflammation and for quantification of the effects of medical intervention on plaque inflammation. FDG-PET of arteries has been proven very reproducible and therefore has high power to show a treatment effect in a smaller group of patients.

A number of complementary methods exist that assess different steps in the atherogenesis like endothelial function (e.g. endo-PAT, glycocalyx measurement), artery wall thickening (e.g. carotid intima media thickness), or coronary atherosclerosis (e.g. coronary artery calcium score). For comparison these other methods will be included as secondary endpoints as they are generally more accessible and less expensive.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized, Placebo-controlled, Parallel
Masking: Double (Participant, Investigator)
Masking Description: Dobbelt-blinded
Primary Purpose: Prevention
Official Title: Effect of Liraglutide on Vascular Inflammation in Type-2 Diabetes: A Randomized, Placebo-controlled, Double-blind, Parallel Clinical PET/CT Trial The Liraflame Trial
Actual Study Start Date : October 1, 2017
Estimated Primary Completion Date : October 1, 2019
Estimated Study Completion Date : October 1, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Liraglutide

Arm Intervention/treatment
Liraglutide Drug: Liraglutide
Liraglutid

placebo Drug: Placebo (for liraglutide)
Placebo (for liraglutide)




Primary Outcome Measures :
  1. Change in vascular inflammation [ Time Frame: baseline to week 26 ]
    Change in vascular inflammation assessed by FDG PET/CT


Secondary Outcome Measures :
  1. Change in Endothelial dysfunction [ Time Frame: baseline to week 26 ]
    Change in endothelial dysfunction assessed with endo-PAT

  2. Change in Endothelial dysfunction [ Time Frame: baseline to week 13 and 26 ]
    Change in endothelial dysfunction, assessed as sublingual glycocalyx measurement

  3. Coronary artery calcium score [ Time Frame: baseline to week 26 ]
    Change coronary artery calcium score (absolute values)

  4. Carotid intima media thickness [ Time Frame: baseline to week 26 ]
    Change in carotid intima media thickness measured by ultrasound


Other Outcome Measures:
  1. Autonomic nervous system function [ Time Frame: baseline to week 26 ]
    Change in cardiovascular autonomic neuropathy indices



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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Given written informed consent
  2. Male or female patients >50 years with type 2 diabetes (WHO criteria)
  3. HbA1c ≥ 48 mmol/mol (6.5 %)
  4. eGFR ≥ 30 ml/min/1.73 m2 (estimated by CKD-epi formula)
  5. Stable glucose-lowering medication (excluding oral glucocorticoids, calcineurin inhibitors, dipeptidyl peptidase 4 (DPP4) inhibitors, glucagon like peptide-1 agonists and other agents, which in the investigator's opinion could interfere with the effect of liraglutide)for at least 4 weeks before the baseline PET/CT
  6. Stable/no treatment of hypercholesterolemia 4 weeks before baseline PET/CT
  7. Must be able to communicate with the investigator and understand informed consent.

Exclusion Criteria:

  1. Type 1 diabetes mellitus
  2. Chronic pancreatitis / previous acute pancreatitis
  3. Known or suspected hypersensitivity to trial product(s) or related products
  4. Treatment 90 days prior to screening with oral glucocorticoids, calcineurin inhibitors, dipeptidyl peptidase 4 (DPP4) inhibitors, glucagon like peptide-1 agonists and other agents, which in the investigator's opinion could interfere with the effect of liraglutide
  5. Cancer or any other clinically significant disorder, except for conditions associated with type 2 diabetes history, which in the investigators opinion could interfere with the results of the trial
  6. Clinical signs of diabetic gastroparesis
  7. Previous bowel resection
  8. Impaired liver function (transaminases > two times upper reference levels)
  9. Inflammatory bowel disease
  10. Weight >150 kg
  11. Females of childbearing potential who are pregnant, breast-feeding, intend to become pregnant or are not using adequate contraceptive methods
  12. Known or suspected abuse of alcohol or narcotics
  13. Subjects with personal or family history of medullary thyroid carcinoma or a personal history of multiple endocrine neoplasia type 2

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03449654


Contacts
Contact: Peter Rossing, MD 30913383 peter.rossing@regionh.dk
Contact: Emilie Zobel 30913496 emilie.hein.zobel@regionh.dk

Locations
Denmark
Steno Diabetes Center Copenhagen Recruiting
Gentofte, Denmark, 2820
Contact: Peter Rossing, MD       peter.rossing@regionh.dk   
Contact: Emilie Zobel, MD       emilie.hein.zobel@regionh.dk   
Principal Investigator: Peter Rossing, MD         
Sub-Investigator: Emilie Zobel, MD         
Sub-Investigator: Tine Willum Hansen, MD         
Sub-Investigator: Viktor Rotbain Curovic         
Sponsors and Collaborators
Steno Diabetes Center
Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet & Cluster for Molecular Imaging, University of Copenhagen, Denmark

Responsible Party: Peter Rossing, MD, chief phycisian, Dr. Med., Steno Diabetes Center
ClinicalTrials.gov Identifier: NCT03449654     History of Changes
Other Study ID Numbers: H-16044546
First Posted: February 28, 2018    Key Record Dates
Last Update Posted: February 28, 2018
Last Verified: February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Inflammation
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Pathologic Processes
Liraglutide
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists