NCT03344692

Effect of Alirocumab on Postprandial Hyperlipemia in Patients With Type 2 Diabetes

Effect of Alirocumab on Postprandial Hyperlipemia in Patients With Type 2 Diabetes : a Randomized, Double-blind, Placebo-controlled, Cross-over Trial"

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 22 (actual)
• Sponsor: Nantes University Hospital · Academic / Other
• Sex: Male
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged over the past decade as a post-transcriptional regulator of the LDL receptor (LDL-R). PCSK9 acts as an endogenous natural inhibitor of the LDL-R pathway. Monoclonal antibodies (mAb) directed against PCSK9, such as Alirocumab, are the most common method of PCSK9 inhibition. The goal of the present study is to assess, in the context of type 2 diabetes, a situation associated with an increased post-prandial hyperlipemia, whether PCSK9 inhibition with Alirocumab affects postprandial intestinal lipoprotein metabolism.

Detailed description

Recently, human monoclonal antibodies directed against PCSK9 have been shown to be effective in reducing LDL cholesterol. Besides the liver, little is known about the role of PCSK9 in the small intestine, a tissue where it is expressed at a high level. Preclinical studies in mice indicate that PCSK9 inhibition reduces post-prandial hyperlipemia. Here, the investigators will test the effect of PCSK9 inhibition with alirocumab, a PCSK9 mAb, on post-prandial hyperlipemia in 24 patients with type 2 diabetes. The investigators will perform a randomized, double-blind, placebo-controlled, cross-over trial with alirocumab 75 mg every two weeks. In the cross-over design, two periods of 10-weeks treatment (i.e. 5 injections) will be separated by a 10-week wash-out period to avoid carry-over effect. The primary endpoint will be the total area under the post-prandial triglycerides concentration-time curve from meal-time until 8h (AUC0-8h) after a standardized meal test. As secondary endpoints, the investigators will explore the effect of alirocumab on plasma lipids, markers of cholesterol absorption and synthesis, and glycemic parameters. This study will help to decipher the function of PCSK9 on intestinal lipoprotein metabolism in human and to determine whether alirocumab can reduce post-prandial hyperlipemia, which is an independent cardiovascular risk factor. From a patient perspective, this study will give some important clues for the management of cardiovascular disease.

Conditions

• Type2 Diabetes

Interventions

Type	Name	Description
DRUG	Alirocumab	prefilled pen containing 75 mg of Praluent (Alirocumab) in 1 ml of solution
OTHER	Placebo	prefilled pen containing 1 ml of solution without Praluent

Timeline

• Start date: 2019-02-12
• Primary completion: 2022-04-28
• Completion: 2022-04-28
• First posted: 2017-11-17
• Last updated: 2022-09-27

Locations

1 site across 1 country: France