Effect of Tredaptive on Serum Lipoproteins and Inflammatory Markers

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Handrean Soran, Central Manchester University Hospitals NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT01054508
First received: January 21, 2010
Last updated: October 10, 2012
Last verified: January 2011
  Purpose

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.


Condition Intervention Phase
Hypercholesterolemia
Drug: nicotinic acid/laropiprant
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: Treatment
Official Title: Effect of Tredaptive on Serum Lipoproteins, Lipoproteins Metabolism, Oxidative Stress and HDL Antioxidant Function

Resource links provided by NLM:


Further study details as provided by Central Manchester University Hospitals NHS Foundation Trust:

Primary Outcome Measures:
  • The investigators expect the majority (90% or more) of patients to achieve a 15% increase in HDL level. [ Time Frame: 14 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Changes in paraoxonase activity, changes in oxidised LDL, changes in glycated LDL, changes in HDL inflammatory index. [ Time Frame: 14 months ] [ Designated as safety issue: No ]

Enrollment: 38
Study Start Date: June 2010
Study Completion Date: January 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Tredaptive
Patients on Tredaptive are expected to have 15% increase in HDL cholesterol.
Drug: nicotinic acid/laropiprant
Nicotinic acid/laropiprant (1g/20mg) daily for 4 weeks, then nicotinic acid/laropiprant (2g/40mg) daily for 8 weeks.
Other Name: Tredaptive

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.

  Eligibility

Ages Eligible for Study:   20 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Men and women who are taking cholesterol-lowering medication (maximum tolerated statins and/or ezetimibe) and who have not reached the recommended LDL target of less than 1.8 mmol/l (70 mg/l). Ezetimibe will be stopped 4 weeks before entering the study.

Exclusion Criteria:

  • Pregnant and/or breast-feeding women. Significant renal impairment (eGFR < 59ml/min). Active liver disease and transaminases > 3 times upper limit of normal range. Patients on fibrates. Patients on Omacor. Patients who are allergic to nicotinic acid.
  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: NCT01054508

Locations
United Kingdom
Manchester Royal Infirmary
Manchester, United Kingdom, M13 9WL
Sponsors and Collaborators
Central Manchester University Hospitals NHS Foundation Trust
Investigators
Principal Investigator: Handrean Soran, MRCP Central Manchester University Hospitals NHS Foundation Trust
  More Information

No publications provided

Responsible Party: Handrean Soran, Dr, Central Manchester University Hospitals NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT01054508     History of Changes
Other Study ID Numbers: TRED012010
Study First Received: January 21, 2010
Last Updated: October 10, 2012
Health Authority: United Kingdom: Research Ethics Committee

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

ClinicalTrials.gov processed this record on July 24, 2014