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CompletedNCT03449654LIRAFLAMEUpdated Jun 11, 2020

Effect of Liraglutide on Vascular Inflammation in Type-2 Diabetes

A Phase 4 interventional study of Liraglutide and Placebo (for liraglutide) in Diabetes Mellitus, Type 2, sponsored by Steno Diabetes Center Copenhagen. Completed at 1 site in Denmark. Open to participants aged 50 Years and older. Per ClinicalTrials.gov, last updated 2020-06-11.

Sponsored by Steno Diabetes Center Copenhagen · Phase 4, Interventional, and Prevention

Phase
Phase 4
Study type
Interventional
Enrollment
102
Allocation
Randomized
Ages
50 Years and older
Sex
All
01

Study 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)

Read the 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.

02

Conditions studied

03

Who can participate

Ages eligible
50 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Phase 4
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
102 participants (actual)

Study arms

  • Other
    Liraglutide

    Drug: Liraglutide

  • Other
    placebo

    Drug: Placebo (for liraglutide)

Interventions

  • DrugLiraglutide

    Liraglutid

  • DrugPlacebo (for liraglutide)

    Placebo (for liraglutide)

05

What researchers measure

Primary outcomes

  1. Change in vascular inflammation

    Change in vascular inflammation assessed by FDG PET/CT

    Time frame: baseline to week 26

Secondary outcomes

  1. Change in Endothelial dysfunction

    Change in endothelial dysfunction assessed with endo-PAT

    Time frame: baseline to week 26

  2. Change in Endothelial dysfunction

    Change in endothelial dysfunction, assessed as sublingual glycocalyx measurement

    Time frame: baseline to week 13 and 26

  3. Coronary artery calcium score

    Change coronary artery calcium score (absolute values)

    Time frame: baseline to week 26

  4. Carotid intima media thickness

    Change in carotid intima media thickness measured by ultrasound

    Time frame: baseline to week 26

Other outcomes

  1. Autonomic nervous system function

    Change in cardiovascular autonomic neuropathy indices

    Time frame: baseline to week 26

06

Study locations

1 site
  • Steno Diabetes Center Copenhagen
    Gentofte, 2820, Denmark
07

References and documents

Publications

  • Zobel EH, Wretlind A, Ripa RS, Rotbain Curovic V, von Scholten BJ, Suvitaival T, Hansen TW, Kjaer A, Legido-Quigley C, Rossing P. Ceramides and phospholipids are downregulated with liraglutide treatment: results from the LiraFlame randomized controlled trial. BMJ Open Diabetes Res Care. 2021 Sep;9(1):e002395. doi: 10.1136/bmjdrc-2021-002395. PubMed 34518158 ↗
  • Ripa RS, Zobel EH, von Scholten BJ, Jensen JK, Binderup T, Diaz LJ, Curovic VR, Hansen TW, Rossing P, Kjaer A. Effect of Liraglutide on Arterial Inflammation Assessed as [18F]FDG Uptake in Patients With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Trial. Circ Cardiovasc Imaging. 2021 Jul;14(7):e012174. doi: 10.1161/CIRCIMAGING.120.012174. Epub 2021 Jun 30. PubMed 34187185 ↗

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT03449654
Lead sponsor
Steno Diabetes Center Copenhagen
Collaborators
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 Copenhagen) — Principal investigator
First posted
Feb 28, 2018
Start date
Oct 26, 2017
Primary completion
Aug 16, 2019
Completion
Aug 16, 2019
Last update
Jun 11, 2020

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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