Randomized, double blind, placebo-controlled trial of ubiquinol in a statin-induced mitochondrial dysfunction model in healthy volunteers.

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 28

Inclusion Criteria

1. Signed informed consent prior to any study-mandated procedure.;2. Males or females aged 40-70 years (inclusive).;3. BMI between: 18-32 kg/m2, minimal weight 50 kg.;4. Expected compliance to the protocol especially with respect to administering simvastatin 40 mg orally once daily for 56 days and ubiquinol 300 mg orally once daily for 28 days.;5. Having a normal day and night rhythm.

Exclusion Criteria

1. Clinically relevant (as determined by the Investigator) cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, rheumatic/joint, psychiatric, renal, and/or other major disease.;2. Clinically significant abnormalities, as judged by the investigator, in laboratory test results (including hepatic and renal panels, complete blood count, chemistry panel and urinalysis). In case of uncertain or questionable results, tests performed during screening may be repeated before the first occasion to confirm eligibility or judged to be clinically irrelevant.;3. Creatine Kinase (CK) > 145 U/L (females) or > 170 U/L (males) in laboratory test results.;4. Presence of any contraindication to have MRI scans performed (e.g. pacemaker, intracranial clips etc.).;5. Having diabetes mellitus or lower extremity peripheral vascular disease, as these conditions may interfere with interpretation of the dynamic 31P-MRS and NIRS of the lower extremity.;6. Recent (within 14 days) or current use of interfering medications: paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), statins and gluco- and/or mineralocorticoid drugs with exception of contraceptives. Usage of other medications will have to be reviewed for interference with the study by the study physician.;7. Participation in a clinical trial within 90 days of screening or more than 4 times in the previous year.;8. Positive test for drugs of abuse at screening or pre-dose.;9. If female, pregnancy (defined as a positive bHCG urine test) or breast-feeding.;10. A history (within 3 months of screening) of alcohol consumption exceeding 2 standard drinks per day on average (1 standard drink = 10 grams of alcohol). ;11. History or symptoms of any significant disease including (but not limited to) neurological, psychiatric, endocrine, cardiovascular, respiratory, gastrointestinal, hepatic, or renal disorder.;12. History or symptoms of any myopathy.;13. A history or presence of porphyria or any other skin disease that is caused by exposure to light. ;14. A history or presence of allergy to 5-aminolevulinic acid or porphyrins.;15. Positive hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV Ab), or human immunodeficiency virus antibody (HIV Ab) at screening.;16. Donation of blood or loss of over 500 mL within 3 months prior to screening.;17. Unwillingness or inability to refrain from consuming aldosterone increasing food or supplements during the study period: bananas, liquorice, glucosamine and palm oil. ;18. Unwillingness or inability to refrain from consuming grapefruit or grapefruit juice.;19. Unwillingness or inability to refrain from consuming alcohol within 48 hours before each visit until the end of that visit.;20. Unwillingness or inability to refrain from tobacco usage within 12 hours before each visit until the end of that visit.;21. Unwillingness or inability to refrain from moderate to strenuous physical activity (e.g. fitness classes, weight lifting, marathon-running etc.) from the screening until the last study visit. ;22. Having a type of lifestyle with no physical activity.;23. Unwillingness or inability to refrain from consuming xanthine containing beverages and foods within 12 hours before each visit and during the study visits.;24. Unwillingness or inability to use contraception if female with child bearing potential.

Study & Design

Study Type: Observational non invasive

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>-PCr recovery time (in seconds) 8 weeks after the start of simvastatin<br /><br>administration.<br /><br>-PCr recovery time (in seconds) after 4 weeks of simvastatin administration.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>-mVO2 (in ml/min/100 ml) measured by NIRS.<br /><br>-mitoPO2 (in mmHg) measured by PpIX-TSLT.<br /><br>-MMP in WBCs (in ratio of aggregated and monomeric JC-1) measured by the JC-1<br /><br>assay.<br /><br>-Serum FGF-21 concentration (in pg/ml).<br /><br>-Hand grip strength (in kg) measured by the Jamar dynamometer and the pinch<br /><br>gauge.<br /><br>-hand grip strength (in kg) measured by the POWERjar©.<br /><br>-Serum creatine kinase concentration.</p><br>