Clinical trial NCT02153879: Characterization of High Density Lipoprotein (HDL) in Type 2 Diabetes (T2D) After Fenofibrate or Niacin Treatment
Official title: Qualitative and Quantitative Characterization of HDL in T2D After Fenofibrate or Niacin Treatment in Spanish Population
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 2 Diabetes Mellitus
Dyslipidemia
Keywords: HDL
Niacin
Fenofibrate
Diabetes
Metabolomics
Lead sponsor: Institut Investigacio Sanitaria Pere Virgili
Sponsor class: OTHER
Collaborators: name: Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders
First posted: 2014-06-03
Enrollment: 30
Sex: ALL
Minimum age (years): 30
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: HDL particles size and number assessed by nuclear magnetic resonance (NMR) and reported as nm and micromol/L
timeFrame: Two periods of 12 weeks treatment according to crossing over design
Secondary outcomes:
measure: Apolipoprotein A1 (Apo A1), apolipoprotein A2 (Apo A2), paraoxonase (PON) HDL concentration (g/l - mg/l)
timeFrame: Two periods of 12 weeks treatment according to crossing over design
Other outcomes:
measure: Lecithin-cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) activity (AU - pmol/h*μl) and mass (microg/ml)
timeFrame: Two periods of 12 weeks treatment according to crossing over design
Locations:
city: Reus
country: Spain
facility: Hospital Universitari Sant Joan
state: Tarragona
Study officials:
affiliation: Institut Investigacio Sanitaria Pere Virgili
name: Luis Masana, Professor
role: STUDY_DIRECTOR
References: