Track topics on Twitter Track topics that are important to you
CVD results from 'hardening of the arteries' when there is a build-up of cholesterol in the walls of blood vessels. LDL is the main carrier of cholesterol in the body. LDL particles are responsible for transporting cholesterol that is deposited in vessel walls. LDL particles can also be altered in structure and turn into an irritant to the vessel walls. The body responds to the irritating effect of LDL by producing substances that result in inflammation. This sequence of events eventually leads to the vessels becoming permanently damaged. HDL has a protective role in CVD. It is associated with the enzyme paraoxonase which protects the body from the damaging effects of altered LDL particles.
Nicotinic acid (niacin) has the ability to lower LDL levels and raise HDL levels thus reducing the incidence of CVD. Our study aims to show that niacin not only has good effects on cholesterol levels but is also able to reduce inflammation. Niacin is often poorly tolerated due to flushing side effect. Tredaptive is a formulation that combines niacin with laropiprant, an agent that reduces flushing hence improving tolerability and compliance.
Patients who are receiving cholesterol-lowering medication and whose LDL levels have not reached the recommended target are recruited to the study. The study will be conducted at the Manchester Royal Infirmary. The study has two consecutive 16 week periods. In each period patients will be randomised to either tredaptive or placebo. They will attend for 5 monitoring visits. Apart from the first visit, fasting blood samples will be taken from them during all subsequent visits.
The design is a placebo-controlled cross-over study. The study has 2 consecutive 16 week periods. If a patient satisfies the inclusion/exclusion criteria and consents to participate in the study, he/she will enter a 4-week placebo run-in period. This is followed by a 12-week treatment period where the patient will be assigned tredaptive or placebo randomly. At the end of the treatment period the patient will enter a second 4-week placebo period before going onto the second 12-week treatment period. Patients who are randomised to placebo in the first treatment period will receive tredaptive in the second treatment period and vice versa. Thus all participating patients will receive active medication for one treatment period in the study.
Patients will continue taking statins for the duration of the study, ensuring the cholesterol-lowering benefits they have from their usual medication are not compromised.
Patients will be recruited from the Lipid Clinic at the Manchester Royal Infirmary. The study will be explained fully to the patients who will have time to ask questions. Information leaflets will be given to patients who will be encouraged to take at least 1 day to discuss the study with their families, friends and general practitioners before consenting.
The study comprises 5 visits. At the first visit, informed consent will be taken from the patients. The visit also includes history taking and physical examination. Subsequent visits take place at the end of 4th and 16th weeks. This is repeated for the second 16 week period. Apart from the first visit, patients will be required to give a blood sample of 50 ml at each of the visits. They will be asked to fast overnight (from 22.00 hours) the day before the visit and blood sampling will be done before midday the following day. Blood will be taken by an experienced doctor or nurse and the only risks involved may be bruising at the puncture site.
Allocation: Randomized, Control: Placebo Control, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Manchester Royal Infirmary
Central Manchester University Hospitals NHS Foundation Trust
Published on BioPortfolio: 2014-08-27T03:16:27-0400
This is a 3-period study. Periods 1 and 2 will evaluate the effects of multiple doses of laropiprant on the antiplatelet effects of clopidogrel and aspirin administered in combination in...
The purpose of this study is to evaluate the potential effects of ER niacin/laropiprant, ER niacin, laropiprant, and placebo over the course of seven days on urinary levels of a metabolite...
This is a 12-week clinical trial in patients with primary hypercholesterolemia or mixed hyperlipidemia, studying the effects of coadministered MK0524B on lipids. There will be 6 scheduled...
The study will be a double-blind, randomized, placebo-controlled, single-center, 2 treatment, 3-way crossover. Subjects will be randomly allocated to a treatment sequence – AAB, ABA or...
Our working hypothesis postulates that lipolysis is a determinant of inflammation in adipose tissue (AT). Inhibition of lipolysis, e.g. using the oldest normolipidemic drug, nicotinic acid...
Hypercholesterolemia is one of the most important contributors to atherosclerosis. Whether hypercholesterolemia also affects the retinal microcirculation is unclear.
Prostaglandin E receptor subtype 4 (EP4) knockout mice develops spontaneous hypercholesterolemia but the detailed mechanisms by which EP4 affects cholesterol homeostasis remains unexplored. We sought ...
Mutations of cholinergic neuronal nicotinic receptors have been identified in the autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), associated with changes on PET images using [F]-F-85380-A...
Cinobufagin (CBG) has been shown to have antinociceptive properties. Nevertheless, the antinociceptive effect and mechanism of CBG are still unclear. The present study was designed to investigate the ...
Bempedoic acid has emerged as a potent inhibitor of ATP-citrate lyase (ACLY), a target for the reduction of LDL cholesterol (LDL-C). We review the impact of bempedoic acid treatment on lipoprotein met...
Drugs that bind to and activate nicotinic cholinergic receptors (RECEPTORS, NICOTINIC). Nicotinic agonists act at postganglionic nicotinic receptors, at neuroeffector junctions in the peripheral nervous system, and at nicotinic receptors in the central nervous system. Agents that function as neuromuscular depolarizing blocking agents are included here because they activate nicotinic receptors, although they are used clinically to block nicotinic transmission.
Drugs that bind to nicotinic cholinergic receptors (RECEPTORS, NICOTINIC) and block the actions of acetylcholine or cholinergic agonists. Nicotinic antagonists block synaptic transmission at autonomic ganglia, the skeletal neuromuscular junction, and at central nervous system nicotinic synapses.
A selective nicotinic cholinergic agonist used as a research tool. DMPP activates nicotinic receptors in autonomic ganglia but has little effect at the neuromuscular junction.
An ester of nicotinic acid that lowers cholesterol and triglycerides in total plasma and in the VLD- and LD-lipoprotein fractions.
A member of the NICOTINIC ACETYLCHOLINE RECEPTOR subfamily of the LIGAND-GATED ION CHANNEL family. It consists entirely of pentameric α7 subunits expressed in the CNS, autonomic nervous system, vascular system, lymphocytes and spleen.
Cardiology is a specialty of internal medicine. Cardiac electrophysiology : Study of the electrical properties and conduction diseases of the heart. Echocardiography : The use of ultrasound to study the mechanical function/physics of the h...
Cholesterol is a waxy steroid metabolite found in the cell membranes and transported in the blood plasma. It is an important structural component of mammalian cell membranes, where it is establishes proper membrane permeability and fluidity. Cholesterol ...