Characterization of High Density Lipoprotein (HDL) in Type 2 Diabetes (T2D) After Fenofibrate or Niacin Treatment

Phase 4

Completed

• Conditions: Type 2 Diabetes Mellitus; Dyslipidemia
• Interventions: Drug: Fenofibrate; Drug: Niacin plus laropiprant

• Registration Number: NCT02153879
• Lead Sponsor: Institut Investigacio Sanitaria Pere Virgili

Brief Summary

The structural and functional alterations of high density lipoproteins (HDL) levels in type 2 diabetes (T2D) patients linked to hypertriglyceridemia, hyperglycemia, insulin resistance, inflammation and oxidation, play a major role in the increased macrovascular risk in these patients. An impaired function of the adipose tissue (AT) in T2D contributes to low HDL concentrations.

Objectives: 1) Quantitative and qualitative characterisation of HDL subclasses by ultracentrifugation, proteomic and metabolomic techniques. 2) To study the relationship between the HDL subclasses, preβ1 HDL and remnant HDL, and clinical determinants of arteriosclerosis. 3) Functional in vitro studies of the HDL subclasses determined in Objective 1. 4) To study the role of AT determining the low HDL levels. 5) To study the impact of HDL increasing drugs on HDL qualitative changes.

Detailed Description

Groups of subjects: a) Diabetic patients with low HDL; b) Non-diabetic patients with low HDL; c) Diabetic patients with normal HDL levels; and d) Non-diabetic patients with normal HDL levels. The studies will be performed after washing out lipid lowering drugs. Intima media thickness (IMT) will be performed in all groups. Main biochemical techniques will be centralised. Isolation and characterisation of HDL subclasses and remnant HDL, as well as a determination and preβ1 HDL will be performed. HDL studies examining HDL proteomic and metabolomic profiles will be performed. Functional studies will determine the effects on the endothelium, inflammation, cholesterol efflux and oxidation according the qualitative changes. These HDL measurements will be repeated in group (a), after they are treated with fibrates or Niacin. HDL metabolism in adipocytes will be extensively studied, and the clinical associations between HDL alterations and plasma AT-derived molecules will be examined.

Study Timeline

• Study Start: 2009-02
• Primary Completion: 2011-12
• Study Completion: 2013-12
• Status Verified: 2014-05
• Study First Submitted: 2014-05-26
• Study First Submitted QC: 2014-06-02
• Last Update Submitted: 2014-06-02
• Study First Posted: 2014-06-03
• Last Update Posted: 2014-06-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• Type 2 diabetic patients
• Age from 30 years to 70 years
• HDL not exceeding 50 mg/dl in men or 60 mg/dl in women

Exclusion Criteria

• to be a smoker
• To be diagnosed with diabetes less than three months before
• To have triglyceride levels above 400 mg/dl
• Glycated hemoglobin higher than 9%
• Albuminuria above 300 mg/mg creatinine
• Chronic kidney disease (eFGR <30 ml/min/1.73 m2)
• Advanced retinopathy
• Neuropathy
• Cardiovascular disease in the last three months
• Chronic liver insufficiency
• Neoplastic disease or any chronic or incapacitating disease

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Fenofibrate	Fenofibrate	Fenofibrate 145 mg/day for 12 weeks
Niacin plus Laropiprant	Niacin plus laropiprant	Niacin 2g/day plus Laropiprant for 12 weeks

Primary Outcome Measures

Name	Time	Method
HDL particles size and number assessed by nuclear magnetic resonance (NMR) and reported as nm and micromol/L	Two periods of 12 weeks treatment according to crossing over design	HDL particles were studied by NMR in T2D patients after treatment with fenofibrate or Niacin

Secondary Outcome Measures

Name	Time	Method
Apolipoprotein A1 (Apo A1), apolipoprotein A2 (Apo A2), paraoxonase (PON) HDL concentration (g/l - mg/l)	Two periods of 12 weeks treatment according to crossing over design	Apoprotein and antioxidant enzymes composition of HDL were also measured

Trial Locations

Locations (1)

Hospital Universitari Sant Joan; 🇪🇸 Reus, Tarragona, Spain