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SAPhIRE Statin Adverse Drug Reaction (STATIN)

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ClinicalTrials.gov Identifier: NCT03042286
Recruitment Status : Unknown
Verified May 2016 by National Heart Centre Singapore.
Recruitment status was:  Recruiting
First Posted : February 3, 2017
Last Update Posted : February 3, 2017
Sponsor:
Collaborator:
National University Hospital, Singapore
Information provided by (Responsible Party):
National Heart Centre Singapore

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
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 Type : Observational
Estimated 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 : March 2015
Estimated Primary Completion Date : May 2017
Estimated Study Completion Date : May 2017

Resource links provided by the National Library of Medicine





Primary Outcome Measures :
  1. Statin drug and metabolite measurement [ Time Frame: 3 to 6 hours ]
    Multiple reaction monitoring via a triple quadropole mass spectrometry (MS) platform


Secondary Outcome Measures :
  1. Pharmacogenomics associated with statin [ Time Frame: 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


Biospecimen Retention:   Samples With DNA
For patients who are sensitive about having genetic material collected, investigators will provide the option of not having their DNA analyzed in the informed consent form.


Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Inpatient and outpatient clinics
Criteria

Inclusion Criteria:

  • For myopathy cohort:

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

For myalgia cohort:

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

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

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

Exclusion Criteria:

  • 1. Unable or unwilling to give written informed consent 2. Subjects who are pregnant or breast feeding

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03042286


Contacts
Contact: Dr Wei Chieh Jack Tan 67048892
Contact: Katherina Oh 67042290

Locations
Singapore
National Heart Centre Singapore Recruiting
Singapore, Singapore, 169609
Contact: Dr Wei Chieh Jack Tan    67048892      
Contact: Katherina Oh    67042290      
Sponsors and Collaborators
National Heart Centre Singapore
National University Hospital, Singapore
Investigators
Principal Investigator: Dr Wei Chieh Jack Tan National Heart Centre Singapore

Responsible Party: National Heart Centre Singapore
ClinicalTrials.gov Identifier: NCT03042286     History of Changes
Other Study ID Numbers: 2014/00856
First Posted: February 3, 2017    Key Record Dates
Last Update Posted: February 3, 2017
Last Verified: May 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by National Heart Centre Singapore:
statin
myalgia
myopathy
adverse drug reactions (ADRs)
pharmacokinetics and pharmacogenetics

Additional relevant MeSH terms:
Muscular Diseases
Drug-Related Side Effects and Adverse Reactions
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Chemically-Induced Disorders
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Lipid Regulating Agents