Effect of Liraglutide on Vascular Inflammation in Type-2 Diabetes

NCT03449654 | Completed Phase 4 DMC

• 1 other identifier: H-16044546
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 1

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)

Conditions

Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (1)

• Change in vascular inflammation

  Change in vascular inflammation assessed by FDG PET/CT

  baseline to week 26

Secondary Outcomes (4)

• Change in Endothelial dysfunction

  baseline to week 26

• Change in Endothelial dysfunction

  baseline to week 13 and 26

• Coronary artery calcium score

  baseline to week 26

• Carotid intima media thickness

  baseline to week 26

Other Outcomes (1)

• Autonomic nervous system function

  baseline to week 26

Study Arms (2)

Liraglutide

OTHER

Drug: Liraglutide

placebo

OTHER

Drug: Placebo (for liraglutide)

Interventions

Liraglutide DRUG

Liraglutid

Liraglutide

Placebo (for liraglutide) DRUG

Placebo (for liraglutide)

placebo

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Steno Diabetes Center Copenhagen: lead
• Rigshospitalet, Denmark: collaborator

Study Sites (1)

Steno Diabetes Center Copenhagen

Gentofte Municipality, 2820, Denmark

Location

Related Publications (4)

• 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.

  PMID: 37752566 DERIVED

• 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.

  PMID: 36992761 DERIVED

• 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.

  PMID: 34518158 DERIVED

• 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.

  PMID: 34187185 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Liraglutide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; 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 Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Dobbelt-blinded
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, chief phycisian, Dr. Med.

Model Details: Randomized, Placebo-controlled, Parallel

Study Record Dates

• First Submitted: December 7, 2017
• First Posted: February 28, 2018
• Study Start: October 26, 2017
• Primary Completion: August 16, 2019
• Study Completion: August 16, 2019
• Last Updated: June 11, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)