Effect of Tredaptive on Serum Lipoproteins and Inflammatory Markers

NCT01054508 | Completed Phase 4

• 2 other identifiers: TRED012010R01049
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hypercholesterolemia

Outcome Measures

Primary Outcomes (1)

• Changes in HDL Levels

  As exactly listed in the protocol, the primary outcome will be changes in HDL-C level. The mean value will be assessed before and after treatment. This level will be compared to the mean value between the placebo and Tredaptive groups.

  14 months

Secondary Outcomes (3)

• Changes in paraoxonase activity

  14 months

• Changes in LDL

  14 months

• Changes in HDL inflammatory index

  14 months

Study Arms (2)

Arm 1: Placebo (4 weeks) --> Placebo (12 weeks) --> Placebo (4 weeks) --> Tredaptive (12 weeks)

OTHER

Placebo (4 weeks) --\> Placebo (12 weeks) --\> Placebo (4 weeks) --\> Tredaptive (12 weeks) There were two interventional periods of 12 weeks during which patients received either Placebo or Tredaptive (nicotinic acid/laropiprant). Patient who received Tredaptive were given dosages of 1g/20mg for 4 weeks followed by 2g/40mg for 8 weeks.

Drug: nicotinic acid/laropiprant

Arm 2: Placebo (4 weeks) --> Tredaptive (12 weeks) --> Placebo (4 weeks) --> Placebo (12 weeks)

OTHER

Placebo (4 weeks) --\> Tredaptive (12 weeks) --\> Placebo (4 weeks) --\> Placebo (12 weeks) There were two interventional periods of 12 weeks during which patients received either Placebo or Tredaptive (nicotinic acid/laropiprant). Patient who received Tredaptive were given dosages of 1g/20mg for 4 weeks followed by 2g/40mg for 8 weeks.

Drug: nicotinic acid/laropiprant

Interventions

nicotinic acid/laropiprant DRUG

Nicotinic acid/laropiprant (1g/20mg) daily for 4 weeks, then nicotinic acid/laropiprant (2g/40mg) daily for 8 weeks.

Also known as: Tredaptive

Arm 1: Placebo (4 weeks) --> Placebo (12 weeks) --> Placebo (4 weeks) --> Tredaptive (12 weeks); Arm 2: Placebo (4 weeks) --> Tredaptive (12 weeks) --> Placebo (4 weeks) --> Placebo (12 weeks)

Eligibility Criteria

• Age: 20 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Manchester University NHS Foundation Trust: lead

Study Sites (1)

Manchester Royal Infirmary

Manchester, M13 9WL, United Kingdom

Location

Related Publications (1)

• Yadav R, Liu Y, Kwok S, Hama S, France M, Eatough R, Pemberton P, Schofield J, Siahmansur TJ, Malik R, Ammori BA, Issa B, Younis N, Donn R, Stevens A, Durrington P, Soran H. Effect of Extended-Release Niacin on High-Density Lipoprotein (HDL) Functionality, Lipoprotein Metabolism, and Mediators of Vascular Inflammation in Statin-Treated Patients. J Am Heart Assoc. 2015 Sep 15;4(9):e001508. doi: 10.1161/JAHA.114.001508.

  PMID: 26374297 DERIVED

MeSH Terms

Conditions

Hypercholesterolemia

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Handrean Soran, MRCP

  Manchester University NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 21, 2010
• First Posted: January 22, 2010
• Study Start: June 1, 2010
• Primary Completion: January 1, 2012
• Study Completion: January 1, 2012
• Last Updated: October 29, 2020

Record last verified: 2020-10

Locations

GB (1)