STATIN: SAPhIRE Statin Adverse Drug Reaction

Sponsor

National Heart Centre Singapore (Other)

Overall Status

Unknown status

CT.gov ID

NCT03042286

Collaborator

National University Hospital, Singapore (Other)

1,500

Enrollment

Location

58.1

Duration (Months)

25.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To find out the pharmacokinetic and genetic risk factors involved in muscular side effects (myalgia) associated with statin therapy. To learn better ways of identifying risk factors associated with muscle side effects during statin therapy. To perform laboratory analysis to identify factors predicting future outcomes. The genetic material, in combination with other medical information and blood tests, will be available to researchers studying genetic and other factors that contribute to myalgia caused in some patient population on statin medication.

Patients on statin are selected for this study. This study will recruit 1500 subjects from National heart Centre Singapore over a period of 2.5 years.

Participation in the full study includes the donation of genetic material. However, subjects have the option of not having blood subjected to genetic analysis and still participate in the study. In this case, blood samples will only be analyzed for the statin drug content.

Condition or Disease	Intervention/Treatment	Phase
Myopathy

Detailed Description

Objective is to characterize the relationship between genetic polymorphisms and inter-individual variability in plasma statin and metabolite concentration(s) and to quantify its contribution towards clinically significant statin induced muscle ADR phenotypes myopathy and/or myalgia in Singapore population. Methodology: This research involves the study of two different kinds of muscle ADRs commonly associated with statin therapy, namely myalgia and myopathy. The study of myalgia will include the recruitment and sample collection (blood)from 3000 subjects from the outpatient clinic at NUH and NHC, who are on either simvastatin or atorvastatin. To identify genetic variants associated with altered stain exposure, investigators will perform an analysis of the drug and metabolite levels in plasma, followed by a genetic analysis of DNA from the blood samples of the recruited subjects. A subgroup of 30 subjects (15 from NUH and 15 from NHC) from this large cohort will be used to study intra-subject variability in statin drug and metabolite exposure. The genetic association analysis of genotype and statin blood measurements will be done using liner regression analysis. To test the hypothesis that related pharmacokinetic variants are associated with myalgia and myopathy, investigators will perform the case-control association analysis using logistic regression to examine the frequency of genetic variant in patients with clinically identified ADRs and compare it to control subjects without any ADRs. A separate cohort of 200 subjects will be recruited for the myopathy study through the NUH outpatient clinic following subject identification through an IRB approved medical records review of patients who were/are any statin drug/dose. Blood samples collected from these patients will be subjected to genetic analysis to identify genetic variants associated with symptomatic phenotypes.

Potential Benefits and risks: The potential benefits of this study include, identifying strong risk factors of statin induced muscle symptoms myalgia/myopathy that should inform clinical practice in minimizing/ managing severity of statin associated muscle symptoms, by identifying patient populations with an increased risk to statin induced myalgia and/or myopathy. This information might ultimately inform treatment decisions including drug selection and dosing and improved prediction of treatment response in a heterogeneous population. The only possible risk in the study is that associated with blood-taking. Obtaining blood can cause pain, bleeding, bruising, or swelling at the site of the needle stick. Fainting sometimes occurs and infection rarely occurs.

Study Design

Study Type:

Observational

Anticipated Enrollment :

1500 participants

Observational Model:

Cohort

Time Perspective:

Other

Official Title:

Study of Pharmacogenomic and Pharmacokinetic Risk Factors Associated With Statin Induced Muscle ADRs (Adverse Drug Reactions) in Singapore Population

Study Start Date :

Mar 1, 2015

Anticipated Primary Completion Date :

Jan 1, 2020

Anticipated Study Completion Date :

Jan 1, 2020

Outcome Measures

Primary Outcome Measures

Statin drug and metabolite measurement [3 to 6 hours]
Multiple reaction monitoring via a triple quadropole mass spectrometry (MS) platform

Secondary Outcome Measures

Pharmacogenomics associated with statin [3 to 6 hours]
DNA extraction will be performed at GIS using Qiagen QIAamp DNA Blood Maxi kit and will be quantified by pico-green serial dilution assays

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

For myopathy cohort:

Subjects are/were on any statin drugs at any dose
Subjects reported/ diagnosed with myopathy =10X normal CK levels
Myopathy in subjects were statin induced

For myalgia cohort:

Subjects are on either Simvastatin or Atorvastatin
If subject experience muscle symptoms without CK elevation (myalgia), it should be statin induced
Compliance to five consecutive statin doses prior to sample collection

For the myalgia subgroup (n=30) for intra-individual variability assessment:

Subjects are on either Simvastatin or Atorvastatin
If subject experience muscle symptoms without CK elevation (myalgia), it should be statin induced
Subjects are willing to provide two blood samples during each of the 3 separate visits
Compliance to five consecutive statin doses prior to sample collection