Retinoic Acid Supplementation and Subjects With Hypercholesterolemia

Effect of Retinoic Acid Supplementation on the HDL-Associated Paraoxonase 1 Activity in Subjects With Hypercholesterolemia: A Randomized, Double-Blinded, Placebo-Controlled Trial

The aim of the study is to investigate the effects of retinoic acid on the HDL-PON1 activity and cholesterol efflux capacity in hypercholesterolemic subjects.

Study Overview

• Status: Completed
• Conditions: Hypercholesterolemia
• Intervention / Treatment: Other: placebo; Dietary supplement: retinoic acid

Detailed Description

Paraoxonase 1 (PON1), an enzyme associated with high-density lipoprotein, is reported to have antioxidant and cardioprotective properties. And all-trans-retinoic acid revealed the ameliorating atherosclerosis effects in many reports.There maybe some correlations between retinoic acid and PON1 activity and the study aim to prove it.

• Study Type: Interventional
• Enrollment (Actual): 130
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University (Northern Campus)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• subject has a fasting total cholesterol concentration between 200 and 310mg/dl.
• subject is between 25 and 65 years of age, inclusive.
• subjects' BMI is between 18.5 kg/m2 and 35 kg/m2.

Exclusion Criteria:

• subject that is pregnant.
• subject that has coronafy artery desease, diabetes mellitus, thyroid disorders, mental disorder, cancer, cirrhosis, renal disease and hepatic desease.
• subject that has had operation less than six months prior to screening visit.
• subject that is smoking.
• subject uses any drugs that could influence the measurement of lipid paramerters or inflammatiory makers.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: control; the participants in this arm are instruted to consume placebo capsules	Other: placebo; During the trial period, the participants are instructed to consume placebo capsules twice daily (30 min after breakfast and supper).The placebo capsules are composed of starch and pigment.
Experimental: treatment; the participants in this arm are instruted to consume retinoic acid capsules	Dietary supplement: retinoic acid; During the trial period, the participants are instructed to consume retinoic acid capsules twice daily (30 min after breakfast and supper).The retinoic acid capsules provided a total daily intake of 10 mg of retinoic acid.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PON1 activity	PON1 activity is assayed in HDL isolated from plasma of subjects from the placebo and retinoic acid groups by using UV spectrophotometry in a 96-well plate format using phenyl acetate or paraoxon as substrates.	changes from baseline in PON1 activity at 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lp-PLA2 activity	Lp-PLA2 activity in apoB-depleted plasma after the sedimentation of all apoB-containing lipoproteins with dextran sulfate-magnesium chloride is determined using the trichloroacetic acid precipitation procedure using 2-thio platelet-activation factor as a substrate.	changes from baseline in Lp-PLA2 activity at 12 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
cholesterol efflux capacity	The cholesterol efflux capacity of the two groups at baseline and after intervention is quantified by a modified method with J774 mouse macrophages. After plated and radiolabeled with 3H-cholesterolper, J774 macrophages are incubation with cAMP and apoB-depleted serum successively. Liquid scintillation counting is used to quantify the efflux of radioactive cholesterol from the cells.	changes from baseline in cholesterol efflux capacity at 12 weeks

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Study Director: Min Xia, PhD, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): May 1, 2015

Study Registration Dates

• First Submitted: July 8, 2015
• First Submitted That Met QC Criteria: July 10, 2015
• First Posted (Estimate): July 15, 2015

Study Record Updates

• Last Update Posted (Estimate): July 15, 2015
• Last Update Submitted That Met QC Criteria: July 10, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia; Antineoplastic Agents; Dermatologic Agents; Keratolytic Agents; Tretinoin
• Other Study ID Numbers: ZXYZM-2