Statin Immune Study

NCT02984293 | Completed Phase 4

• 2 other identifiers: 2016CV0516/ES/0128
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Drug Intolerance

Keywords

Atorvastatin; LILRB5; Statin intolerance

Outcome Measures

Primary Outcomes (1)

• 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.

Study Arms (2)

Atorvastatin

ACTIVE COMPARATOR

The participants will receive atorvastatin (80 mg) orally once daily for 28 days.

Drug: Atorvastatin

Placebo

PLACEBO COMPARATOR

The participants will receive matched placebo orally once daily for 28 days.

Drug: Placebo

Interventions

Atorvastatin DRUG

Atorvastatin 80 mg once daily for 28 days.

Atorvastatin

Placebo DRUG

Placebo once daily for 28 days.

Placebo

Eligibility Criteria

• Age: 40 Years - 69 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 40-69 years
• Statin-naïve
• White European
• Healthy
• Acceptable laboratory test results

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Dundee: lead
• NHS Tayside: collaborator

Study Sites (1)

University of Dundee

Dundee, DD1 9SY, United Kingdom

Location

Related Publications (2)

• Dube 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, Rheaume 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.

  PMID: 25214527 BACKGROUND

• 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.

  PMID: 24897241 BACKGROUND

MeSH Terms

Interventions

Atorvastatin

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids

Study Officials

• Colin NA Palmer, PhD FSB FRSE

  University of Dundee

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: December 2, 2016
• First Posted: December 6, 2016
• Study Start: April 17, 2017
• Primary Completion: November 3, 2017
• Study Completion: November 3, 2017
• Last Updated: December 3, 2018

Record last verified: 2018-03

Data Sharing

• IPD Sharing: Will share

Locations

GB (1)