Sixteen children were screened. Three children did not meet the QMT reliability inclusion criterion. Thirteen children 5 to 10 years old, mean age 8.03 ±1.64, were enrolled in the lead-in phase, but one obese child was removed from the study due to failure to achieve target CoQ10 levels despite several months of dose escalation to up to 800 mg/day. Twelve participants completed the trial.
gives the average values of the primary and secondary outcome measures at baseline, end of lead-in period, and end of month 6 for all subjects completing the study. There was a significant (p=0.03) increase in the average total QMT score from TI3 to the end of treatment (from 11.7 to 12.7 lbs or 8.5%). Analysis of individual QMT scores changes shows an average 1.01 lbs increase in the QMT score from LI3 to Month 6 with a standard error of 1.4 lbs. This was reproduced with the analysis in log scale (p=0.046).
Table 1 Average values of primary and secondary outcomes at baseline, end of Lead-In period, and Treatment Month 6 showing increases in muscle strength testing with significant improvements seen in QMT total score at Treatment Month 6 compared to Lead-In 3 (p=0.03). (more ...)
shows the observed and fitted values of the total QMT score throughout the treatment period. The total QMT score increased by 0.06 lbs/month during the treatment period (slope p=0.28). This trend supports the beneficial effect of CoQ10 on muscle strength.
Figure 1 Plots of mean ± standard deviation of the observed data at each of the time points from Lead-In 3 to Treatment Month 6 and fitted trend lines obtained in the trend analysis via mixed-effects models. Lead-In 3 is the period immediately prior to (more ...)
Among all 12 subjects who completed the study, nine subjects (age 5.2 to 10.2 years) showed an increase in total QMT score from baseline. Among them, six subjects showed at least a 10% increase in QMT total scores; one subject increased 8%, one increased 6%, and one increased 2% in QMT total score (). The 3 patients who did not show an improvement were between 7.5 to 8.7 years old. The percent increase results are generally consistent within the QMT arm (11%), leg (8%) and hand grip (9%) scores. Correlation analysis showed that there was no significant correlation between the individual response and baseline disease severity in total QMT or any other strength parameters. In addition, the spread of the age of the patients who showed some improvement included only 2 children under the age of 7. This suggests that the effect measured was not due to a “honeymoon” period.
Individual QMT total score (lbs) for 12 patients from Baseline to Treatment Month 6 showing an overall increase in muscle strength of 9 subjects.
There were no significant changes in cardiac parameters during the trial. At the start of the trial, the ejection fraction (62±4%), left ventricular internal diameter (3.8±0.2 cm) and posterior wall thickness (0.6±0.1 cm) during diastole and electrocardiograms were normal and did not change significantly at the end of the trial.
There was no correlation between baseline CQ10 serum levels and disease severity as measured by the baseline total QMT score. There were also no significant correlations between age at baseline or disease severity and response to CoQ10 treatment.
There was significant variability between subjects in achieving target serum concentrations of CoQ10. To achieve the same level, children required doses ranging between 90 and 510 mg per day. The average dose/kg weight at the end of the study was 27.8 mg/kg ranging from 8.7 to 48.4 mg/kg. Initial CoQ10 serum levels varied between 0.6 to 3.6 μg/ml, when the initial dose was 90 mg, and 1.3 to 8.1 μg/ml, when the initial dose was changed to 400 mg. Serum levels increased more rapidly and remained more constant when CoQ10 was co-delivered with a small fatty snack, presumably due to increased bioavailability of the CoQ10. Serum levels were maintained between 2.6 and 9.2 μg/ml during the 6-month treatment phase for all subjects. There was no correlation between baseline total QMT score and dose required to maintain the therapeutic level.
There were no serious adverse events. One patient developed a headache of moderate intensity associated with high blood levels of CoQ10 (7.37 μg/ml, dose 400 mg, 20 mg/kg). The event resolved with a decrease of the dose to 200 mg per day (serum level 3.66 μg/ml).