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

Type 2 Diabetes Mellitus Clinical Trial

— LOWHDL  

Official title:

Qualitative and Quantitative Characterization of HDL in T2D After Fenofibrate or Niacin Treatment in Spanish Population

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02153879
• Other study ID #: IISPV-HUSJR-LOWHDL
• Status: Completed
• Phase: Phase 4
• First received: May 26, 2014
• Last updated: June 2, 2014
• Start date: February 2009
• Est. completion date: December 2013

Study information

• Verified date: May 2014
• Source: Institut Investigacio Sanitaria Pere Virgili
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Hospital Universitari de Sant Joan de Reus-CEICSpain: Department of Health of the Generalitat of CataloniaSpain: Ministerio de Sanidad, Servicios Sociales e Igualdad
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: December 2013
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years to 70 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Dyslipidemia
• Dyslipidemias
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Fenofibrate
fenofibrate 145/day for 12 weeks
• Niacin plus laropiprant
Niacin 2 g/day plus Laropiprant for 12 weeks

Locations

Country	Name	City	State
Spain	Hospital Universitari Sant Joan	Reus	Tarragona

Sponsors (2)

Lead Sponsor	Collaborator
Institut Investigacio Sanitaria Pere Virgili	Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Lecithin-cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) activity (AU - pmol/h*µl) and mass (microg/ml)	LCAT and CETP mass and activities were measured;	Two periods of 12 weeks treatment according to crossing over design	No
Primary	HDL particles size and number assessed by nuclear magnetic resonance (NMR) and reported as nm and micromol/L	HDL particles were studied by NMR in T2D patients after treatment with fenofibrate or Niacin	Two periods of 12 weeks treatment according to crossing over design	No
Secondary	Apolipoprotein A1 (Apo A1), apolipoprotein A2 (Apo A2), paraoxonase (PON) HDL concentration (g/l - mg/l)	Apoprotein and antioxidant enzymes composition of HDL were also measured	Two periods of 12 weeks treatment according to crossing over design	No

External Links

•   Institut Investigacio Sanitaria Pere Virgili- Pere Virgili Health Research institute