Asymp and symp statin users will undergo baseline measurements of skeletal muscle mitochondrial function and muscle function after which they will be switched to a single-blind placebo intervention for 12 weeks. Then the same measurements will be repeated. Hereafter, only the symptomatic statin users will continue with the intervention en will be randomely allocated to: atorvastatin, atorvastin+exercise or placebo+exercise for another 12 weeks. Then the same measurements will be repeated again.
Conditions
Interventions
Trade Name: Atorvastatin
Pharmaceutical Form: Capsule
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use
Sponsors
Radboud university medical centre
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: age: 18-70 years old current statin users mentally able/allowed to give informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 45 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: familial hypercholesterolemia impaired liver function hereditary muscle defect kidney insufficiency unwillingness to abstain from grapefruit juice during the intervention
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •Do statins accumulate in muscle and cause inhibition of complex III activity of the mitochondrial respiratory chain ? •Is the severity of the muscle function decline determined by the total statin concentration in muscle, as well as by the pharmacokinetic properties of the statin? •Could aerobic exercise training on top of statin treatment offer protection against statin-associated muscle symptoms by positively influencing muscle metabolism? ;Secondary Objective: • Can we identify clinically relevant predictive parameters that could facilitate the diagnosis of Statin-associated muscle symptoms in clinical practice (e.g. plasma markers, muscle function, muscle gene expression, whole body energy metabolism)?;Primary end point(s): o Energy generating capacity of muscle mitochondria (in muscle biopsy) (see ex vivo measurement in 8.3 study procedures for the detailed biochemical assays that will be carried out in the fresh muscle tissue). o Muscle function (= muscle force, contractile speed, relaxation and fatigability) o Cardiorespiratory fitness (incremental cycling test) ;Timepoint(s) of evaluation of this end point: baseline (in both symptomatic and asymptomatic statin users); at12 weeks: after a 12-week single-blind placebo intervention (in both symptomatic and asymptomatic statin users); after 24 weeks: after a subsequent 12 weeks of double-blind randomized intervention with atorvastatin, atorvastatin+exercise or placebo+exercise in symptomatic statin users only | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): o Mitochondrial number (in muscle biopsy) o Blood parameters: lipid profile (total cholesterol, HDL-, LDL-cholesterol, triglycerides), liver enzymes (ASAT, ALAT, gamma-GT), kidney function (creatinin), creatine kinase, WBC count, pyruvate and lactate o Statin concentrations in the muscle and blood o Questionnaires on muscle complaints (Short-form McGill pain questionnaire and Short-form Brief Pain Inventory) ;Timepoint(s) of evaluation of this end point: Mitochondrial number: baseline, 12 weeks, 24 weeks blood parameters, statin concentrations, questionnaires: every three weeks | — |
Countries
Netherlands
Contacts
Public Contactdr. Silvie Timmers
Radboud university medical centre
Outcome results
None listed