Statin Immune Study

Study Overview
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Brief Summary
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Statins are widely used drugs to treat hypercholesterolaemia. In general, they are very safe drugs. However, up to one third of statin users can experience muscle symptoms, which are most commonly mild without any conventional laboratory signs of muscle damage. However, these muscle symptoms can often lead to poor compliance to the cholesterol-lowering therapy, reducing its effectiveness. Recent data has highlighted the potential role of immune system in development of statin-induced muscle pain. Variation in the LILRB5 gene has been associated with statin intolerance. We aim to investigate the impact of LILRB5 genetic variability in tolerability and immune response to atorvastatin in healthy volunteers. The study is being undertaken at the Tayside Institute for Cardiovascular Research (TICR) in Ninewells Hospital, Dundee. We will recruit participants who have donated a sample to GoSHARE study. The participants will be healthy, and recruited according to their genotype of LILRB5 (information available from GoSHARE). The volunteers will then enter a randomised cross-over study with two treatment periods. During treatment period one, all participants will be commenced on atorvastatin or placebo (a dummy drug). Before and at the end of the treatment period, blood and urine samples will be taken and a muscle symptoms questionnaire will be completed to assess the tolerability and immune response to the study drug exposure. After four weeks, the study drug is stopped for a washout period of three weeks before cross-over commences. Thereafter, during treatment period two, the alternate study drug will be started, and tolerability will be assessed similar to that in period one. The study will last approximately 11 weeks. The volunteers have a total of 5 visits to the TICR.

Official Title
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Impact of LILRB5 Genotype on Immune Response to Atorvastatin

Conditions
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Drug Intolerance

Intervention / Treatment
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* Drug: Atorvastatin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 40-69 years Statin-naïve White European Healthy Acceptable laboratory test results Exclusion Criteria: Significant disease Regular drug therapy Recent involvement (<30 days) in a CTIMP Inability/unwillingness to comply with the protocol Carry the rare variant of the CKM polymorphism rs11559024 Unable to consent Woman of childbearing potential (i.e. premenopausal female capable of becoming pregnant)

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 69 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Atorvastatin<br>The participants will receive atorvastatin (80 mg) orally once daily for 28 days. | Drug: Atorvastatin<br>* Atorvastatin 80 mg once daily for 28 days.<br>|
| Placebo Comparator: Placebo<br>The participants will receive matched placebo orally once daily for 28 days. | Drug: Placebo<br>* Placebo once daily for 28 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary outcome will be the change in CK levels at the end of the treatment from baseline in both treatment periods. |  | Measured at baseline (day 0) and day 29 of both treatment periods. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atorvastatin, LILRB5, Statin intolerance