Statin Immune Study (ImmunoStat)

• ClinicalTrials.gov Identifier: NCT02984293
• Recruitment Status: Completed
• First Posted: December 6, 2016
• Last Update Posted: December 3, 2018
• Sponsor: University of Dundee
• Collaborator: NHS Tayside
• Information provided by (Responsible Party): University of Dundee

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Drug Intolerance	Drug: Atorvastatin; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 18 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Basic Science
• Official Title: Impact of LILRB5 Genotype on Immune Response to Atorvastatin
• Actual Study Start Date: April 17, 2017
• Actual Primary Completion Date: November 3, 2017
• Actual Study Completion Date: November 3, 2017

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Atorvastatin; The participants will receive atorvastatin (80 mg) orally once daily for 28 days.	Drug: Atorvastatin; Atorvastatin 80 mg once daily for 28 days.
Placebo Comparator: Placebo; The participants will receive matched placebo orally once daily for 28 days.	Drug: Placebo; Placebo once daily for 28 days.

Outcome Measures

Primary Outcome Measures :

1. The primary outcome will be the change in CK levels at the end of the treatment from baseline in both treatment periods. [ Time Frame: Measured at baseline (day 0) and day 29 of both treatment periods. ]

Eligibility Criteria

• Ages Eligible for Study: 40 Years to 69 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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)

Contacts and Locations

Locations

United Kingdom

University of Dundee

Dundee, United Kingdom, DD1 9SY

Sponsors and Collaborators

University of Dundee

NHS Tayside

Investigators

• Study Chair: Colin NA Palmer, PhD FSB FRSE; University of Dundee

More Information

Publications:

Dubé MP, Zetler R, Barhdadi A, Brown AM, Mongrain I, Normand V, Laplante N, Asselin G, Zada YF, Provost S, Bergeron J, Kouz S, Dufour R, Diaz A, de Denus S, Turgeon J, Rhéaume E, Phillips MS, Tardif JC. CKM and LILRB5 are associated with serum levels of creatine kinase. Circ Cardiovasc Genet. 2014 Dec;7(6):880-6. doi: 10.1161/CIRCGENETICS.113.000395. Epub 2014 Sep 11.

Alfirevic A, Neely D, Armitage J, Chinoy H, Cooper RG, Laaksonen R, Carr DF, Bloch KM, Fahy J, Hanson A, Yue QY, Wadelius M, Maitland-van Der Zee AH, Voora D, Psaty BM, Palmer CN, Pirmohamed M. Phenotype standardization for statin-induced myotoxicity. Clin Pharmacol Ther. 2014 Oct;96(4):470-6. doi: 10.1038/clpt.2014.121. Epub 2014 Jun 4.

• Responsible Party: University of Dundee
• ClinicalTrials.gov Identifier: NCT02984293
• Other Study ID Numbers: 2016CV05; 16/ES/0128 ( Other Identifier: East of Scotland Research Ethics Service )
• First Posted: December 6, 2016
• Last Update Posted: December 3, 2018
• Last Verified: March 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: As per GoSHARE tissue bank protocol, the data derived from the existing samples will be returned to the tissue bank for research use.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of Dundee:

Atorvastatin; LILRB5; Statin intolerance

Additional relevant MeSH terms:

Atorvastatin; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Enzyme Inhibitors