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Diabetes Mellitus, Type 2Phase 4LIRAFLAMENCT03449654

Effect of Liraglutide on Vascular Inflammation in Type-2 Diabetes

A Phase 4 study testing Liraglutide in people with Diabetes Mellitus, Type 2, run by Steno Diabetes Center Copenhagen at 1 site in Denmark.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 50 years and older
Conditions the study is for
Diabetes Mellitus, Type 2
What is being tested?
Liraglutide
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
102 participants
Where
1 siteDenmark
Study dates
26 Oct 2017to 16 Aug 2019
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 50 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Given written informed consent
  • Male or female patients >50 years with type 2 diabetes (WHO criteria)
  • HbA1c ≥ 48 mmol/mol (6.5 %)
  • eGFR ≥ 30 ml/min/1.73 m2 (estimated by CKD-epi formula)
  • 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
  • Stable/no treatment of hypercholesterolemia 4 weeks before baseline PET/CT
  • Must be able to communicate with the investigator and understand informed consent.

Who cannot join

  • Type 1 diabetes mellitus
  • Chronic pancreatitis / previous acute pancreatitis
  • Known or suspected hypersensitivity to trial product(s) or related products
  • 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
  • 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
  • Clinical signs of diabetic gastroparesis
Show all 13Show fewer
  • Previous bowel resection
  • Impaired liver function (transaminases > two times upper reference levels)
  • Inflammatory bowel disease
  • Weight >150 kg
  • Females of childbearing potential who are pregnant, breast-feeding, intend to become pregnant or are not using adequate contraceptive methods
  • Known or suspected abuse of alcohol or narcotics
  • Subjects with personal or family history of medullary thyroid carcinoma or a personal history of multiple endocrine neoplasia type 2

Trial locations and contacts

1 site in 1 country.

Denmark1 site

  • Steno Diabetes Center Copenhagen

    Gentofte Municipality, 2820

Other trials in Denmark

About this study

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

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.

Being tested
Liraglutide, Placebo (for liraglutide)
Medical subject headings
Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LiraglutideDrug

    Liraglutid

  • Placebo (for liraglutide)Drug

    Placebo (for liraglutide)

Study groups in NCT03449654
Study groupRoleWhat they receive
LiraglutideOtherNot described
Receives: Drug: Liraglutide
placeboOtherNot described
Receives: Drug: Placebo (for liraglutide)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in vascular inflammation

    Change in vascular inflammation assessed by FDG PET/CT

    Measured: baseline to week 26

Secondary outcomes (4)

  1. Change in Endothelial dysfunction

    Change in endothelial dysfunction assessed with endo-PAT

    Measured: baseline to week 26

  2. Change in Endothelial dysfunction

    Change in endothelial dysfunction, assessed as sublingual glycocalyx measurement

    Measured: baseline to week 13 and 26

  3. Coronary artery calcium score

    Change coronary artery calcium score (absolute values)

    Measured: baseline to week 26

  4. Carotid intima media thickness

    Change in carotid intima media thickness measured by ultrasound

    Measured: baseline to week 26

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Feb 2018
  2. Study start26 Oct 2017
  3. Primary completion16 Aug 2019
  4. Study completion16 Aug 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Model description
Randomized, Placebo-controlled, Parallel
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
102 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03449654
Sponsor's protocol ID
H-16044546
Acronym
LIRAFLAME
Status last verified
Jun 2020
First submitted
7 Dec 2017
Last updated
11 Jun 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Wretlind A, Curovic VR, de Zawadzki A, Suvitaival T, Xu J, Zobel EH, von Scholten BJ, Ripa RS, Kjaer A, Hansen TW, Vilsboll T, Vestergaard H, Rossing P, Legido-Quigley C. Ceramides are decreased after liraglutide treatment in people with type 2 diabetes: a post hoc analysis of two randomized clinical trials. Lipids Health Dis. 2023 Sep 26;22(1):160. doi: 10.1186/s12944-023-01922-z.

    PubMed 37752566

  • Wretlind A, Zobel EH, de Zawadzki A, Ripa RS, Curovic VR, von Scholten BJ, Mattila IM, Hansen TW, Kjaer A, Vestergaard H, Rossing P, Legido-Quigley C. Liraglutide Lowers Palmitoleate Levels in Type 2 Diabetes. A Post Hoc Analysis of the LIRAFLAME Randomized Placebo-Controlled Trial. Front Clin Diabetes Healthc. 2022 Mar 4;3:856485. doi: 10.3389/fcdhc.2022.856485. eCollection 2022.

    PubMed 36992761

  • 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

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Liraglutide in people with Diabetes Mellitus, Type 2, run by Steno Diabetes Center Copenhagen at 1 site in Denmark.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in vascular inflammation (time frame: baseline to week 26). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03449654, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2020.

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