Clinical trial NCT00414531: Investigations on Differences in Atorvastatin Metabolites Ratios as a Diagnostic Tool in Detecting Atorvastatin Induced Myotoxicity
Official title: Investigations on Differences in Atorvastatin Metabolites Ratios as a Diagnostic Tool in Detecting Atorvastatin Induced Myotoxicity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Myotoxicity of Atorvastatin Treatment
Lead sponsor: University of Oslo School of Pharmacy
Sponsor class: OTHER
First posted: 2006-12-21
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: The primary objective of the study is to investigate the ratios of p-hydroxyatorvastatin to atorvastatin in patients receiving atorvastatin treatment, who experience muscle adverse events, to elucidate whether differences in this ratio might have a positive or negative predictive value in diagnosing atorvastatin muscle toxicity.

Detailed description: The primary objective of the study is to investigate the ratios of p-hydroxyatorvastatin to atorvastatin in patients receiving atorvastatin treatment, who experience muscle adverse events, to elucidate whether differences in this ratio might have a positive or negative predictive value in diagnosing atorvastatin muscle toxicity. If this is shown, measurements of atorvastatin metabolites from patients experiencing muscle adverse events might be a valuable diagnostic tool to diagnose myopathy associated with statin treatment. The primary endpoint cut off level for present myotoxicity has been set to a ratio of p-hydroxyatorvastatin /atorvastatin of 0.15 from the previously performed pilot study (Unpublished data, Herman M et al). Values at or above this ratio will be considered as clinical significant indicia of statin related myopathy.

Secondary objectives include descriptively investigation of drug to metabolite cut off ratio for atorvastatin lactone/atorvastatin. Whether other cut off values, both for p-hydroxyatorvastatin as well as for atorvastatin lactone, give more precise identification of patients that are experiencing statin related myopathy compared to controls will also be investigated.

Explorative objectives of the study are to investigate possible in vitro phenotypic differences in isolated muscle cells from patients experiencing muscle toxicity compared to patients not experiencing muscle toxicity. If there are genetic differences between patients experiencing myotoxicity and those not, this difference is likely to show as phenotypic differences in in vitro studies of isolated muscle cells. If such phenotypic differences are present in vitro possible mechanistic causes will be further investigated.

Eligibility criteria: Inclusion Criteria:

* Suspected atorvastatin induced muscle adverse events.
* Signed informed consent.
* 18 years of age or older.
* Able to donate blood samples.

Primary outcomes:
measure: ratio of p-hydroxyatorvastatin to atorvastatin vs. myopathy
timeFrame: march 2009
Secondary outcomes:
measure: ratio of atorvastatin lactone to atorvastatin vs. myopathy
timeFrame: march 2009
Other outcomes:
Locations:
city: Oslo
country: Norway
facility: Rikshospitalet-Radiumhospitalet HF, Lipid clinic
Study officials:
affiliation: Universtiy of Oslo
name: Anders Åsberg, Ph.D.
role: STUDY_DIRECTOR
References:
citation: Skottheim IB, Bogsrud MP, Hermann M, Retterstol K, Asberg A. Atorvastatin metabolite measurements as a diagnostic tool for statin-induced myopathy. Mol Diagn Ther. 2011 Aug 1;15(4):221-7. doi: 10.1007/BF03256413.