Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials
Trial record 3 of 10 for:    "familial HDL deficiency" OR "Hypoalphalipoproteinemias"

Short-term Effect of Extended-release Niacin on Endothelial Function.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Andrei Carvalho Sposito, University of Campinas, Brazil
ClinicalTrials.gov Identifier:
NCT01942291
First received: September 10, 2013
Last updated: NA
Last verified: September 2013
History: No changes posted
  Purpose

Individuals with reduced plasma concentration of high-density lipoprotein (HDL) cholesterol are more susceptible to oxidative stress and often present reduced endothelial function, which has been mainly related to this susceptibility. Studies in animal and cell models have demonstrated that niacin activates both GPR-109A in leukocytes and heme oxygenase-1 (HO-1) pathway promoting strong anti-inflammatory and anti-oxidative effects. . In this context, the aim of this study was to investigate the short-term effect of niacin on endothelial function and verify the existence of interaction of PGD2 receptor antagonist, i.e. laropiprant (LRPT), in subjects with low HDL-cholesterol (HDL -C).


Condition Intervention Phase
Hypoalphalipoproteinemia
Drug: Niacin
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Official Title: Short-term Effect of Extended-release Niacin With and Without the Addition of Laropiprant on Endothelial Function

Resource links provided by NLM:


Further study details as provided by University of Campinas, Brazil:

Primary Outcome Measures:
  • The short-term effect of niacin on endothelial function. [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    Endothelial-dependent vasodilation was assessed by ischemia-induced reactive hyperemia of the brachial artery by using an ultrasound equipment


Secondary Outcome Measures:
  • Plasma C-reactive protein levels [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    Systemic inflammatory activity as estimated by the plasma concentration of C-reactive protein

  • HDL-C and HDL size [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    Plasma concentration of high-density lipoprotein (HDL) cholesterol and HDL size


Enrollment: 18
Study Start Date: March 2012
Study Completion Date: June 2013
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Niacin/Laropiprant
Extended-release niacin 1g/day associated with Laropiprant 1g/20mg (ERN/LRPT, Cordaptive, Merck, Sao Paulo, Brazil)
Drug: Niacin
The study was randomized, double-blind, controlled, using a 2-way crossover design with both treatment periods and washout time lasting 7 days. Subjects were allocated by simple randomization to extended-release niacin 1g/day alone (ERN, Metri, Libbs Farmacêutica, São Paulo, Brazil) or niacin associated with LRPT 1g/20mg (ERN/LRPT, Cordaptive, Merck, São Paulo, Brazil).
Other Names:
  • Nicotinic acid
  • Vitamin B3
Experimental: Niacin
Extended-release niacin 1g/day alone (ERN, Metri, Libbs Farmaceutica, Sao Paulo, Brazil)
Drug: Niacin
The study was randomized, double-blind, controlled, using a 2-way crossover design with both treatment periods and washout time lasting 7 days. Subjects were allocated by simple randomization to extended-release niacin 1g/day alone (ERN, Metri, Libbs Farmacêutica, São Paulo, Brazil) or niacin associated with LRPT 1g/20mg (ERN/LRPT, Cordaptive, Merck, São Paulo, Brazil).
Other Names:
  • Nicotinic acid
  • Vitamin B3

Detailed Description:

Study design and treatments The study was randomized, double-blind, controlled, using a 2-way crossover design with both treatment periods and washout time lasting 7 days. Subjects were allocated by simple randomization to extended-release niacin 1g/day alone (ERN, Metri, Libbs Farmacêutica, São Paulo, Brazil) or niacin associated with LRPT 1g/20mg (ERN/LRPT, Cordaptive, Merck, São Paulo, Brazil). Medications were kindly supplied by Libbs and Merck. Plasma samples and brachial artery reactivity were obtained at baseline, 7th day of treatment 1, 7th day after washout and 7th day of treatment 2.

Study Measurements The following blood measurements were performed using the Modular Hitachi system and Roche Diagnostics (Mannheim, Germany) reagents: glucose (GOD-PAP), triglycerides (TG)(GPO-PAP), HDL-C (HDL-C plus 3rd generation) and C-reactive protein (CRP) (high-sensitivity CRP, Cardiophase, Dade Behring, Marburg, Germany). LDL cholesterol was calculated by the Friedewald formula. HDL size was measured by laser scattering (Zetasizer - Nanoseries DTS 1060, Malvern Instruments, Worcestershire, UK). Total and direct bilirrubin was measured by the Jendrassik-Grof method (Roche/Hitachi analyzer).

The cholesteryl ester transfer protein activity was measured by an endogenous assay. Aliquots of the whole plasma (in which LCAT activity was inhibited by DTNB 9 μL/mL) were added to HDL-[3H]cholesteryl ester fractions and simultaneously incubated at 4°C and 37°C for 4h. Apo-B containing lipoproteins, present in the incubation mixture, were then precipitated; the CE radioactivity in the supernatant represented the net rate at which CE mass was transferred and values expressed as percent of [3H] cholesteryl ester transferred/4 hours depended upon the plasma concentrations of HDL, TG-rich lipoproteins and CETP simultaneously.

Endothelial-dependent vasodilation was assessed by ischemia-induced reactive hyperemia. Briefly, after 12-hour overnight fasting patients were examined at 8 a.m. in a quiet room at 22ºC by using a ultrasound equipment Vivid i (GE Healthcare, Wauwatosa, WI, USA) with a high-resolution (up to 13 MHz) vascular probe (12l-RS, GE Healthcare, Wauwatosa, WI, USA) in B-mode. The cardiac cycles were monitored simultaneously by electrocardiography coupled to the equipment. Flow-mediated dilation (FMD) was assessed after 5-minutes inflation of a cuff placed below the transducer, 50 mm Hg above the systolic blood pressure. Two-dimensional images of the brachial artery were obtained during 5 minutes from the longitudinal axis approximately 5-10 cm above the antecubital fossa. The maximum expansion of the diameter of the brachial artery was measured in triplicate at the peak of the T wave of the cardiac cycle before the interruption of the flow and post deflation.

  Eligibility

Ages Eligible for Study:   20 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • asymptomatic individuals
  • plasma HDL-C levels <40 mg/dL

Exclusion Criteria:

  • symptomatic atherosclerotic disease
  • diabetes
  • liver disease
  • renal disease
  • thyroid dysfunction
  • indication for or use of lipid-lowering treatment in the last six months
  • use of anti-inflammatory treatment in the last 30 days
  • current or previous diagnosis of cancer or immune inflammatory diseases
  • chronic obstructive pulmonary disease
  • infectious disease manifested in the last 3 months
  • body mass index ≥ 26 kg/m2
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01942291

Locations
Brazil
University of Campinas
Campinas, SP, Brazil, 13083-887
Sponsors and Collaborators
University of Campinas, Brazil
Investigators
Principal Investigator: Andrei C Sposito, PhD University of Campinas
  More Information

No publications provided by University of Campinas, Brazil

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Andrei Carvalho Sposito, Professor, University of Campinas, Brazil
ClinicalTrials.gov Identifier: NCT01942291     History of Changes
Other Study ID Numbers: Unicamp845/2011
Study First Received: September 10, 2013
Last Updated: September 10, 2013
Health Authority: Brazil: Ethics Committee

Keywords provided by University of Campinas, Brazil:
Niacin
Endothelial function
Laropiprant
HDL

Additional relevant MeSH terms:
Hypoalphalipoproteinemias
Dyslipidemias
Genetic Diseases, Inborn
Hypolipoproteinemias
Lipid Metabolism Disorders
Lipid Metabolism, Inborn Errors
Metabolic Diseases
Metabolism, Inborn Errors
Niacin
Niacinamide
Nicotinic Acids
Antimetabolites
Cardiovascular Agents
Growth Substances
Hypolipidemic Agents
Lipid Regulating Agents
Micronutrients
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Vasodilator Agents
Vitamin B Complex
Vitamins

ClinicalTrials.gov processed this record on November 20, 2014