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

• ClinicalTrials.gov Identifier: NCT02153879
• Recruitment Status: Completed
• First Posted: June 3, 2014
• Last Update Posted: June 3, 2014
• Sponsor: Institut Investigacio Sanitaria Pere Virgili
• Collaborator: Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders
• Information provided by (Responsible Party): LUIS MASANA, MD, Institut Investigacio Sanitaria Pere Virgili

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Type 2 Diabetes Mellitus; Dyslipidemia	Drug: Fenofibrate; Drug: Niacin plus laropiprant	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Qualitative and Quantitative Characterization of HDL in T2D After Fenofibrate or Niacin Treatment in Spanish Population
• Study Start Date: February 2009
• Actual Primary Completion Date: December 2011
• Actual Study Completion Date: December 2013

Arms and Interventions

Arm	Intervention/treatment
Experimental: Fenofibrate; Fenofibrate 145 mg/day for 12 weeks	Drug: Fenofibrate; fenofibrate 145/day for 12 weeks; Other Name: Secalip
Experimental: Niacin plus Laropiprant; Niacin 2g/day plus Laropiprant for 12 weeks	Drug: Niacin plus laropiprant; Niacin 2 g/day plus Laropiprant for 12 weeks; Other Name: Tredaptive

Outcome Measures

Primary Outcome Measures :

1. HDL particles size and number assessed by nuclear magnetic resonance (NMR) and reported as nm and micromol/L [ Time Frame: 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 :

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

Other Outcome Measures:

1. Lecithin-cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) activity (AU - pmol/h*μl) and mass (microg/ml) [ Time Frame: Two periods of 12 weeks treatment according to crossing over design ]
   LCAT and CETP mass and activities were measured;

Eligibility Criteria

• Ages Eligible for Study: 30 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Spain

Hospital Universitari Sant Joan

Reus, Tarragona, Spain, 43204

Sponsors and Collaborators

Institut Investigacio Sanitaria Pere Virgili

Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders

Investigators

• Study Director: Luis Masana, Professor; Institut Investigacio Sanitaria Pere Virgili

More Information

Additional Information:

Institut Investigacio Sanitaria Pere Virgili- Pere Virgili Health Research institute 

• Responsible Party: LUIS MASANA, MD, Professor, Institut Investigacio Sanitaria Pere Virgili
• ClinicalTrials.gov Identifier: NCT02153879
• Other Study ID Numbers: IISPV-HUSJR-LOWHDL
• First Posted: June 3, 2014
• Last Update Posted: June 3, 2014
• Last Verified: May 2014

Keywords provided by LUIS MASANA, MD, Institut Investigacio Sanitaria Pere Virgili:

HDL; Niacin; Fenofibrate; Diabetes; Metabolomics

Additional relevant MeSH terms:

Diabetes Mellitus, Type 2; Dyslipidemias; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Lipid Metabolism Disorders; Niacin; Fenofibrate; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents; Vasodilator Agents; Vitamin B Complex; Vitamins; Micronutrients; Nutrients; Growth Substances; Physiological Effects of Drugs