Effect of Tredaptive on Serum Lipoproteins and Inflammatory Markers
Condition: Hypercholesterolemia
MeSH terms: Hypercholesterolemia
Study type: Interventional
Phase: Phase 4

Summary: 
      Cardiovascular disease (CVD) is associated with high levels of low-density lipoprotein (LDL)
      cholesterol and low levels of high-density lipoprotein (HDL) cholesterol.

      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.
    

Detailed description: 
      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.
    

Intervention name(s): nicotinic acid/laropiprant
Intervention type(s): Drug
Intervention description(s): Nicotinic acid/laropiprant (1g/20mg) daily for 4 weeks, then nicotinic acid/laropiprant (2g/40mg) daily for 8 weeks.
Other intervention name(s): Tredaptive
Intervention MeSH terms: Nicotinic Acids; Niacin; Niacinamide
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment