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CLINICAL TRIALS
SECTION EDITOR: IRA SHOULSON, MD
Randomized, Double-blind, Placebo-Controlled Trial
on Symptomatic Effects of Coenzyme Q10
in Parkinson Disease
Alexander Storch, MD; Wolfgang H. Jost, MD; Peter Vieregge, MD; Jörg Spiegel, MD; Wolfgang Greulich, MD;
Joachim Durner, MD; Thomas Müller, MD; Andreas Kupsch, MD; Henning Henningsen, MD; Wolfgang H. Oertel, MD;
Gerd Fuchs, MD; Wilfried Kuhn, MD; Petra Niklowitz, MD; Rainer Koch, PhD; Birgit Herting, MD;
Heinz Reichmann, MD; for the German Coenzyme Q10 Study Group
Background: Major hallmarks in the pathophysiology
of Parkinson disease are cellular energy depletion and oxidative stress leading to cellular dysfunction and death.
Coenzyme Q10 (CoQ10) is an electron acceptor bridging
mitochondrial complexes I and II/III and a potent antioxidant that consistently partially recovers the function
of dopaminergic neurons.
Objective: To determine whether nanoparticular CoQ10
is safe and displays symptomatic effects in patients with
midstage Parkinson disease without motor fluctuations.
Design: Multicenter, randomized, double-blind, placebocontrolled, stratified, parallel-group, single-dose trial.
Setting: Academic and nonacademic movement disorder clinics.
Patients: One hundred thirty-one patients with Parkinson disease without motor fluctuations and a stable
antiparkinsonian treatment.
Intervention: Random assignment to placebo or nanoparticular CoQ10 (100 mg 3 times a day) for a treatment
period of 3 months. Stratification criterion was levodopa treatment.
Main Outcome Measure: The subjects underwent evaluation with the Unified Parkinson’s Disease Rating Scale
(UPDRS) at each visit on a monthly basis. The primary outcome variable was the change of the sum score of the UPDRS
parts II and III between the baseline and 3-month visits.
Results: One hundred thirty-one subjects were randomized according to the protocol. The mean changes of the
sum UPDRS parts II/III score were −3.69 for the placebo
group and −3.33 for the CoQ10 group (P=.82). Statistical analysis according to the stratification did not result
in significant changes of the primary outcome variable.
No secondary outcome measure showed a significant
change between the placebo group and the CoQ10 group.
The frequency and quality of adverse events were similar in both treatment groups.
Conclusions: Nanoparticular CoQ10 at a dosage of 300
mg/d is safe and well tolerated and leads to plasma levels similar to 1200 mg/d of standard formulations. Add-on
CoQ10 does not display symptomatic effects in midstage
Parkinson disease.
Trial Registration: clinicaltrials.gov Identifier:
NCT00180037
Arch Neurol. 2007;64:(doi:10.1001/archneur.64.7.nct60005)
P
Author Affiliations are listed at
the end of this article.
Group Information: The
German Coenzyme Q10 Study
Group members are listed on
page E6.
ARKINSON DISEASE (PD) IS A
neurodegenerative disorder
characterized by a progressive loss of dopaminergic
neurons within the substantia nigra pars compacta.1 Although the
pathogenesis of PD is not fully understood, the recognition that 1-methyl-4phenyl-1,2,3,6-tetrahydropyridine (MPTP)
can induce a parkinsonian syndrome by
inhibiting mitochondrial complex I activity generated the idea that a disorder of the
mitochondrial respiratory chain is involved in PD.2 Indeed, a 30% to 40% re-
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duction of complex I activity in substantia nigra of PD brains has been found,3 a
defect that does not affect other parts of
the brain.4 Coenzyme Q10 (CoQ10) is an antioxidant, an obligatory cofactor of mitochondrial uncoupling proteins, and a bioenergetic agent in the mitochondrial
respiratory chain, where it transfers electrons from complexes I/II to complex III.5,6
Because of these functions, CoQ10 has attracted attention concerning neuroprotective actions in neurodegenerative disorders linked to mitochondrial defects or
oxidative stress, such as Huntington disWWW.ARCHNEUROL.COM
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ease and PD.7 Beal et al8 demonstrated that taking oral
CoQ10 reduces the loss of dopamine and dopaminergic
axons in the striatum of aged parkinsonian mice treated
with MPTP. On the other hand, CoQ10 might also improve dysfunctions of cells suffering from energy depletion and subsequently generate symptomatic effects as
demonstrated in various mitochondrial disorders.9-11
The study of the Parkinson Study Group12 investigating possible protective effects of CoQ10 in early PD demonstrated that high doses of CoQ10 slow the progressive
deterioration of functions in PD measured by the total
score on the Unified Parkinson’s Disease Rating Scale
(UPDRS) but neither improve motor functions nor postpone the start of levodopa treatment.12 Due to the lack
of a washout phase and the fast and predominant effects
of CoQ10 on activities of daily living (ADL) scores, it is
not yet fully clear whether these effects might be a consequence of functional or antidepressive effects rather than
neuroprotective actions.12-14 We therefore undertook a
randomized, double-blind, placebo-controlled trial on
symptomatic effects of nanoparticular CoQ10 in stable patients with midstage PD. We assumed that CoQ10 showed
a symptomatic effect by improving cellular functions, including their synthesis capacity of dopamine from levodopa, and therefore stratified our study by a comedication of levodopa.
METHODS
TRIAL DESIGN
Our multicenter, placebo-controlled, randomized, stratified,
double-blind, parallel-group, single-dose clinical trial was conceived and organized by the German Coenzyme Q10 Study Group
and sponsored by the German Parkinson Association (Neuss,
Germany) and MSE Pharmazeutika GmbH (Bad Homburg, Germany). The subjects were enrolled between September 2003
and January 2005 at 13 movement disorder clinics. The study
was approved by the institutional review boards at participating sites, and all subjects gave written informed consent. An
independent contract research organization monitored all data,
the patients’ safety, and the tolerability of the study drug and
continuously informed the principal investigator (H.R.) about
all safety issues. There was no prespecified guideline for recommending either modification or termination of the trial. The
trial was registered in a public trials registry on September 9,
2005.
SUBJECTS
Subjects were between 40 and 75 years of age, had received the
diagnosis of PD according to the UK Brain Bank criteria,15 had
a rating on the modified Hoehn-Yahr scale16 between II and III
and 16 points or more on the UPDRS motor score,16 and were
on stable antiparkinsonian medication with or without levodopa for at least 4 weeks prior to study enrollment. Patients
were excluded if they had been exposed to CoQ10 during the
last 3 months prior to study inclusion; were taking more than
149 IU of vitamin E (100 mg of D-␣-tocopherol) or calcium,
magnesium, and/or other vitamins for more than 3 months prior
to study inclusion; were receiving cholesterol-lowering drugs,
thyroid hormones, antiarrhythmic compounds, warfarin, metformin, or clozapine; had an identifiable cause of parkinsonism or signs for atypical parkinsonian disorders; had hypothy-
roidism or current evidence of epilepsy or psychosis; or had
levodopa-induced motor fluctuations or dyskinesias.
Subjects were randomly assigned to nanoparticular CoQ10
suspension (100 mg 3 times a day; Nanoquinon from MSE
Pharmazeutika) or matching placebo for a treatment period of
3 months centrally by the contract research organization according to a randomization list generated by 1 of us (R.K.). Randomization was stratified by comedication of levodopa. After
3 months, the subjects underwent a withdrawal from study drug
for 2 months and a final assessment of the severity of the symptoms of PD was made. Doses of levodopa and all other antiparkinsonian medications were kept constant throughout the
study.
OUTCOMES
Efficacy assessments were made by treating investigators, who
were blinded to the treatment assignment, at the screening, baseline, and interim visits (at the end of months 1, 2, and 3) and
at the end of the washout phase at the end of month 5. The
prespecified primary efficacy variable was the change of the sum
of the UPDRS parts II and III (ADL and motor components)16
between baseline to interim visit at month 3 (end-oftreatment visit). Secondary clinical outcome variables were the
scores for 6 instruments: The total UPDRS score,16 the Hoehn
and Yahr score,16 the Schwab and England ADL score,16 the Parkinson’s Disease Questionnaire (PDQ39) score,17 the Global
Clinical Impression score, and the Montgomery-Asberg Depression Rating Scale.18
Safety evaluations included recording of adverse events, results of laboratory tests (obtained at screening, baseline, the
interim visit at the end of month 3, and the end-of-study visit),
electrocardiographic results (baseline visit and interim visit after 3 months), and vital signs (all visits). Adverse events were
coded with the use of a standard glossary.
Plasma CoQ10 levels were obtained at baseline, at the endof-treatment visit (after 3 months), and after the washout phase
of 2 months. Subjects were asked to refrain from taking the study
medication on the day of the mentioned visits to obtain plasma
levels representative of a steady state. The samples were kept
at each site at −20°C to −80°C until shipped on dry ice to the
laboratory at the Department of Pediatrics, University of WittenHerdecke, Witten, Germany. Assays for plasma levels of total
CoQ10 were performed as previously described.19
SAMPLE SIZE RATIONALE
AND STATISTICAL ANALYSES
A sample size of 53 subjects per treatment group (106 total)
was calculated to provide 95% power to detect a difference in
the mean change of the sum score of UPDRS parts II and III of
7.0 units (20% of baseline score) between the placebo and the
CoQ10 group using a 1-tailed t test at the .05 level of significance. The SD was estimated at 11.0 units for this calculation.
Allowing a dropout rate of 20% of the subjects enrolled, we chose
a sample size of 132 subjects (ie, 66 subjects in each of the 2
treatment groups).
We used the intention-to-treat principle in the analysis of
the primary outcome variable and the adverse effects with the
last-observation-carried-forward method to enter values if no
follow-up information was available. We further analyzed both
the primary and all secondary outcome variables using the perprotocol population.
Results are presented as mean±SD or as median values and
the range. Variations in the primary outcome variable (UPDRS
ADL and motor sum score) between baseline and end of treatment period were compared between the placebo and CoQ10
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Table. Baseline Characteristics of the Study Subjects
131 Subjects underwent
randomization
Characteristic
64 Assigned to coenzyme Q10
67 Assigned to placebo
21 Without
levodopa
(31.1%)
46 With
levodopa
(68.7%)
12 Prematurely discontinued
ooothe study
7 Had a protocol violation
oo(10.4%)
3 Had adverse events (4.5%)
2 Withdrew consent (3.0%)
19
Completed
trial (90.5%)
36
Completed
trial (78.3%)
43 With
levodopa
(67.2%)
21 Without
levodopa
(32.8%)
13 Prematurely discontinued
ooothe study
11 Had a protocol violation
ooo(17.2%)
02 Had adverse events
ooo(3.1%)
34
Completed
trial (79.1%)
17
Completed
trial (81.0%)
51 Completed trial according
to protocol (79.1%)
55 Completed trial according
to protocol (82.1%)
Figure 1. Patient flowchart.
groups using a t test and analysis of covariance, adjusting for
the baseline value as a covariate. Variations in all secondary outcome variables were compared between the baseline and endof-treatment periods and between the placebo and CoQ10 groups
using a t test (continuous variables) or a ␹2 test (discrete variables). Both tests were adjusted using the Bonferroni technique. Frequencies of adverse effects were compared between
groups by means of Fisher exact test. All reported P values are
2-sided.
RESULTS
STUDY POPULATION
Of a total of 131 subjects enrolled (randomized) in the
study, 106 (81%) completed the trial according to the
protocol (Figure 1). Sixty-four subjects were assigned
to receive CoQ10 and 67 to receive placebo. The strata
consist of 21 subjects without levodopa treatment in both
groups and 43 and 46 subjects receiving levodopa in the
CoQ10 and placebo groups, respectively. Baseline demographic and background characteristics are summarized in the Table; there were no significant differences
in these characteristics between the 2 groups as well as
between strata. All randomized patients received at least
1 dose of study drug. One third of patients (37 of 131,
or 34.9%) had coexisting medical conditions at baseline. The most common were cardiovascular disorders
(in 20 patients, or 15.3%), such as hypertension and arrhythmia, and others (in 15, or 11.5%), such as infections, glaucoma, and sleep apnea. Among the patients who
were receiving central nervous system drugs at baseline
(130 patients, or 99.3%), all patients were receiving antiparkinsonian medication, and the dose of dopaminergic
Placebo
Group
(n = 67)
Coenzyme
Q10 Group
(n = 64)
Male sex, No. (%)
47 (70.1)
44 (68.7)
Age, mean ± SD, y
62.3 ± 7.9
60.7 ± 9.1
BMI, mean ± SD
25.23 ± 3.59 25.52 ± 3.02
Severity of disease, mean ± SDc
Total UPDRS score
38.6 ± 15.3 35.5 ± 12.8
Mental component, part I
1.9 ± 1.6
1.6 ± 1.4
ADL component, part II
10.5 ± 5.3
9.1 ± 4.9
Motor component, part III
25.0 ± 9.1
23.5 ± 7.9
ADL/motor sum score, parts II/III 35.5 ± 13.6 32.6 ± 11.8
Schwab and England scale score
83.6 ± 9.6
84.1 ± 9.8
Hoehn and Yahr scale score
2.3 ± 0.4
2.3 ± 0.4
Antiparkinsonian medication,
No. (%)
Levodopa therapy
46 (68.7)
43 (67.2)
Dopamine agonists
55 (82.1)
54 (84.4)
Other antiparkinsonian agents
16 (23.9)
16 (25.0)
Coenzyme Q10 plasma levels,
0.94 ± 0.34 0.99 ± 0.44
µg/mLd
P
Value
.86a
.31b
.63b
.22b
.25b
.13b
.31b
.19b
.78b
.93b
.86a
.73a
.88a
.49b
Abbreviations: ADL, activities of daily living, BMI, body mass index
(calculated as weight in kilograms divided by height in meters squared);
UPDRS, Unified Parkinson’s Disease Rating Scale.
a 2
␹ Test.
b
t Test.
c
The Hoehn and Yahr scale, which ranges from 1 to 5, represents stages of
Parkinson disease. On the UPDRS and the Hoehn and Yahr scale, higher
numbers indicate a greater severity of the impairment. The Schwab and England
scale was used to assess ADL, which range from 0 to 100, with 100 indicating
normal.
d
Because of intermediate thawing of some plasma samples from one site, all
samples from this site were excluded from the analyses and only 51 samples
per group were included in baseline coenzyme Q10 level measurements.
drugs was kept constant in 60 patients in the CoQ10 group
and in 64 patients in the placebo group; changes of antiparkinsonian medication led to exclusion from the perprotocol population in 4 and 3 subjects, respectively. All
randomized patients were included in the primary efficacy and safety analysis (intent-to-treat population), but
13 patients were excluded from the CoQ10 group and 12
from the placebo group for additional per-protocol population analyses of primary and all secondary efficacy measures due to protocol violations or discontinuation of the
study (Figure 1). The per-protocol population was similarly constituted and matched between groups compared
with the intent-to-treat population.
EFFICACY
The mean changes of the primary outcome measure (combined UPDRS part II/III scale scores) from baseline visit
to the end-of-treatment visit after 3 months for all randomized subjects were −3.69 for the placebo group and
−3.33 for the CoQ10 group, indicating an improvement
in ADL/motor function in both groups (with P⬍.001 and
P=.007 for the placebo and CoQ10 group, respectively;
Figure 2). The prespecified primary efficacy analysis was
a t test for the difference between these mean changes,
which was not significant with P=.82 (2-sided). Covariance analysis adjusted for baseline values also showed
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Sum Score of UPDRS Part II/III (ADL and Motor Components)
45
Placebo group
Coenzyme Q10 group
40
35
30
25
–1
0
1
2
3
4
5
Treatment Period, mo
Figure 2. Unified Parkinson’s Disease Rating Scale (UPDRS) part II and III
(activities of daily living [ADL] and motor scales) sum score (primary
outcome measure). The sum scores of all randomized patients (last
observation carried forward) are expressed as mean±SD. Higher scores
indicate more severe features of parkinsonian syndrome. Statistical analyses
using a t test revealed statistically significant reduction of the scores from
baseline (month 0) to month 3 (end of treatment period) in both groups
(P ⬍.001 and P = .007 for the placebo and coenzyme Q10 groups,
respectively) but no statistically significant differences between both
treatment groups (P =.82).
no significant differences between the primary outcome
measure of the treatment groups (P = .25). Similar results were obtained with the per-protocol population
showing a significant reduction of the UPDRS II/III scale
scores (−4.4 and −2.8 for the placebo and CoQ10 groups
[P⬍.001 and P=.03], respectively), but no significant differences between groups (P = .32; t test, 2-sided). Analyzing the primary efficacy data according to the stratifications criterion (levodopa treatment) also revealed no
significant difference between treatment groups or strata.
Together, the efficacy data demonstrated a significant placebo effect in both treatment groups, which is very well
known from clinical trials in PD.20
Analysis of all secondary outcome measures (including ADL and depression scores) of the per-protocol population (with or without stratification) using a covariance
analysis adjusted for baseline values revealed no significant differences between the placebo and the CoQ10 group.
Solely, the Hoehn and Yahr scale scores decreased significantly in the CoQ10 group (−0.16, P=.008) but not in the
placebo group (−0.01, P=.85) with a significant difference between groups (P=.04). Analysis according to the
stratification revealed significant changes only in the levodopa stratum of the CoQ10 group (−0.24, P=.007).
TOLERABILITY AND SAFETY
In general, CoQ10 was well tolerated. The percentage of
subjects receiving CoQ10 who reported any adverse event
(20 [31.3%]) was not significantly different from that in
the placebo group (19 [28.4%]; P = .44). Most frequently reported adverse events (occurring in at least 2
patients [3%]) included viral infection (affecting 6 patients [9.0%] in the placebo group and 2 [3.1%] of those
in the CoQ10 group), diarrhea (affecting 1 [1.5%] and 5
[7.8%]), acute hearing loss (1 [1.5%] and 1 [1.6%]), night
sweats (1 [1.5%] and 1 [1.6%]), nausea (1 [1.5%] and 1
[1.6%]), and bronchitis (0 and 3 [4.7%]). Most adverse
events were mild or moderate. The occurrence of serious adverse events was similar in both groups (2 patients in the placebo group, 4 patients in the CoQ10 group).
There was 1 death 2 days before the end of the washout
phase in the CoQ10 group, most likely due to myocardial infarction (patient was included in the analyses). Adverse events that contributed to premature withdrawal
or interruption of the study drug included nausea/
dizziness (1 patient in each group), diarrhea and hallucinations (1 patient each in the placebo group), and pyrosis (1 patient in the CoQ10 group). There were no
significant differences between the groups with respect
to clinically relevant changes in the results of laboratory
tests, electrocardiograms, and vital sign measurements.
PLASMA LEVELS OF CoQ10
The group receiving CoQ10 had a significant increase in
the mean plasma level of CoQ10 from baseline to the
end-of-treatment visit after 3 months with a mean±SD
baseline and treatment phase level of 0.99 ± 0.44 mg/L
(1.15±0.51 nmol/mL) and 4.46±2.07 mg/L (5.17±2.40
nmol/mL) CoQ10, respectively (P⬍.001; Figure 3). The
mean level in the CoQ10 group returned to baseline level
after withdrawal of CoQ10 for 2 months (0.94 ± 0.37
mg/L [1.09±0.43 nmol/mL] CoQ10). There was no significant change of mean CoQ10 plasma level in the placebo group.
COMMENT
Although we demonstrated a significant increase in plasma
levels of CoQ10 toward levels observed with high doses of
standard CoQ10 formulations in PD and other disorders,
our study failed to show improvement of PD symptoms and
did not meet its primary or secondary end points. Our study
further demonstrated that 300 mg/d of nanoparticular CoQ10
is safe and well tolerated in patients with PD already taking various antiparkinsonian medications.
Shults and colleagues12 aimed to investigate the protective effects of CoQ10 in early PD and showed that 1200
mg/d of CoQ10 slows the progressive deterioration of functions in PD measured by the total UPDRS score but neither alters the UPDRS motor score nor postpones the start
of levodopa treatment. However, restoration of mitochondrial respiration and reduction of oxidative stress
by CoQ10 could also improve cellular dysfunction induced by cellular energy depletion as observed in PD.3,4,10
Thus, CoQ10 could have symptomatic effects in PD similar to those seen in mitochondrial disorders.9,11 Indeed,
Shults and coworkers12 did not fully exclude symptomatic effects because th e CoQ10 had not been washed out
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12
Placebo group
Coenzyme Q10 group
Coenzyme Q10 Plasma Level, nmol/mL
10
8
6
4
2
0
Baseline
Month 3
Follow-up
Figure 3. Box plots of plasma coenzyme Q10 levels from the placebo and
coenzyme Q10 groups. The plots show the minimum, first quartile, median,
third quartile, and maximum of coenzyme Q10 levels for each group of
patients at baseline, at the interim visit at end of month 3 (end of treatment
period), and after 2 months of follow-up. Circles represent the mean values.
The numbers of samples available from the baseline, treatment phase, and
follow-up visit were 51, 46, and 42 for the placebo group and 51, 46, and 44
for the coenzyme Q10 group. Diamonds indicate the outliers.
before testing the outcome of CoQ10 treatment. Moreover, fast and predominant effects of CoQ10 particularly
on the ADL scores might be a consequence of functional or antidepressive effects of CoQ10.12 Consistently,
one pilot trial investigating the add-on of 360 mg/d of
CoQ10 for 1 month also demonstrated mild improvement of the total UPDRS score but not of motor functions,13 while a small study in patients with early PD using
up to 1500 mg/d of CoQ10 for 6 months showed mild improvement of motor functions.14 However, this latter study
was open label, it lacked a placebo group, and the data
were not statistically significant when using multiple comparison techniques.14 In our trial, we observed no effects of add-on CoQ10 either on motor functions or on
ADL or depressive symptoms. However, we chose a short
treatment period of 3 months to exclude relevant disease progression interfering with our data on symptomatic effects of CoQ10 and powered our study to detect
a mean change of the sum score of UPDRS part II/III of
7 units (20% of baseline score). Therefore, we cannot exclude mild symptomatic changes occurring after a longer
treatment period.
The results of various studies indicate that the dosage and the resulting plasma and presumably brain levels of CoQ10 might be important determinants of its
effectiveness. The baseline CoQ10 plasma levels of approximately 1 mg/L in both treatment groups were well
matched and in the range previously described in healthy
controls, PD, and other conditions.14,21,22 Shults and colleagues12,23 reported lower baseline levels of CoQ10 of about
0.5 mg/L, most likely due to different analyzing tech-
niques. We used here an improved lipophilic emulsion
of nanoparticular CoQ10 at a dosage of 300 mg/d, leading to a significant increase of the mean plasma level to
4.5 mg/L, which is similar to levels previously described
with 1200 mg/d of a standard formulation.12,23 Explanations for the relatively mild increase of CoQ10 plasma levels in the trial by Shults and colleagues12,24 might include different pharmacokinetics and the antagonism
of CoQ10 uptake by high doses of vitamin E. However,
the CoQ10 plasma levels in the present trial were reported to significantly increase the electron transport chain
activity in mitochondria from patients with PD.12 Additionally, case series of patients with hereditary CoQ10 deficiency or mitochondrial disorders showed clinical improvement with dosages of CoQ10 similar to or even less
than those used in our study.9,10,25 In vitro data indicate
that similar concentrations of CoQ10 could counteract
1-methyl-4-phenylpyridinium toxicity toward dopaminergic cells and partially ameliorate mitochondrial defects in fibroblasts from patients with PD.26,27 Although
we do not know the CoQ10 brain levels and do not have
good indicators for the CoQ10 action in the brain, these
data suggest that insufficient CoQ10 levels are most likely
not responsible for the absence of symptomatic effects
in PD.
The nanoparticular formulation of CoQ10 used in the
present study at high dosages was well tolerated and safe
in patients with midstage PD simultaneously treated
with their regular antiparkinsonian medication. We
found no significant differences in the frequency and
quality of adverse events in the CoQ10 group compared
with the placebo control group. These data are in line
with previous studies using various formulations of
CoQ10 in patients with PD12,14,23 and other neurological
and nonneurological conditions.9,25,28
To our knowledge, this is the first trial systematically
investigating the safety and symptomatic efficacy of high
doses of CoQ10 in patients with PD. Since we did not find
symptomatic effects of CoQ10 in PD, our study does not
support the hypothesis that restoring the impaired energy metabolism of the diseased dopaminergic neurons
leads to symptomatic benefits in PD. Future studies will
need to explore the protective effects of CoQ10 at the highest effective dose (equivalent to ⬇2400 mg/d of a standard formulation23) over a long treatment period and in
a large cohort of patients both sufficient to clearly define the protective potential of this compound in PD.
CONCLUSIONS
Nanoparticular CoQ10 at a dosage of 300 mg/d is safe and
well tolerated in patients with PD and leads to plasma
levels sufficient to exert intracellular effects and similar
to 1200 mg/d of standard formulations. Adding CoQ10
to standard antiparkinsonian medication does not display symptomatic effects in midstage PD without motor
fluctuations.
Accepted for Publication: December 15, 2006.
Published Online: May 14, 2007 (doi:10.1001/archneur
.64.7.nct60005).
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German Coenzyme Q10 Study Group
Participating Centers and Investigators
Andreas Kupsch, MD; Elmar Lobsien, MD, Department
of Neurology, Charite Berlin, Berlin, Germany; Thomas
Müller, MD; Elvira Heitmann, MD; Anita Mackowiak,
MD; Ulrike Theodoridis, MD, Department of Neurology, Ruhr-University of Bochum, Bochum, Germany;
Heinz Reichmann, MD (principal investigator); Birgit
Herting, MD; Verena Fürer, MD; Susann Junghanns, MD,
Department of Neurology, Technical University of
Dresden, Dresden, Germany; Wolfgang Greulich, MD;
Kerstin Schmidt-Dabrock, MD, Department of Neurology, Klinikum Ambrock, Hagen, Germany; Stefan Jung,
MD; Jörg Spiegel, MD, Department of Neurology, University of Homburg, Homburg/Saar, Germany; Joachim
Durner, MD; Karin Junginger, MD, Department of Neurology, Fachklinik Ichenhausen, Ichenhausen, Germany; Peter Vieregge, MD, Department of Neurology,
Klinikum Lemgo, Lemgo, Germany; Henning Henningsen, MD, Department of Neurology, Klinikum Lüneburg, Lüneburg, Germany; Wolfgang H. Oertel, MD,
Department of Neurology, University of Marburg, Marburg, Germany; Wilfried Kuhn, MD, Department of Neurology, Leopoldina Krankenhaus, Schweinfurt, Germany; Alexander Storch, MD; Michael Sabolek, MD,
Department of Neurology, University of Ulm, Ulm, Germany; Wolfgang H. Jost, MD; Elvira Heitmann, MD, Department of Neurology, Deutsche Klinik fuer Diagnostik, Wiesbaden, Germany; Gerd Fuchs, MD, Fachklinik
Wolfach, Wolfach, Germany.
Pharmacokinetic Measurements
Petra Niklowitz, MD, Department of Pediatrics, Vestische Kinderklinik Datteln, University of WittenHerdecke, Witten, Germany.
Biostatistics and Clinical Trial Coordination
Rainer Koch, PhD, Department of Biometrics and Medical Informatics, Technical University of Dresden; Birgit
Herting, MD; Alexander Storch, MD; Heinz Reichmann,
MD (principal investigator), Department of Neurology,
Technical University of Dresden; Gert Gammel, PhD;
Rainer Koch, PhD, MSE Pharmazeutika GmbH, Bad Homburg, Germany; Gisela Rauch-Petz, MD, independent contract research organization, Munich, Germany.
Safety Monitoring Committee
Gisela Rauch-Petz, MD, independent contract research
organization, Munich; Heinz Reichmann, MD, Department of Neurology, Technical University of Dresden.
Author Affiliations: Department of Neurology, University of Ulm, Ulm, Germany (Dr Storch); Departments of
Neurology (Drs Storch, Herting, and Reichmann) and Biometrics and Medical Informatics (Dr Koch), Technical
University of Dresden, Dresden, Germany; Department
of Neurology, Deutsche Klinik fuer Diagnostik, Wiesbaden, Germany (Dr Jost); Department of Neurology,
Klinikum Lemgo, Lemgo, Germany (Dr Vieregge); Department of Neurology, University of Homburg, Homburg/
Saar, German (Dr Spiegel); Department of Neurology,
Klinikum Ambrock, Hagen, Germany (Dr Greulich); Department of Neurology, Fachklinik Ichenhausen, Ichen-
hausen, Germany (Dr Durner); Department of Neurology, Ruhr-University of Bochum, Bochum, Germany
(Dr Müller); Department of Neurology, Charite Berlin,
Berlin, Germany (Dr Kupsch); Department of Neurology, Klinikum Lüneburg, Lüneburg, Germany (Dr
Henningsen); Department of Neurology, University of
Marburg, Marburg, Germany (Dr Oertel); Fachklinik Wolfach, Wolfach, Germany (Dr Fuchs); Department of Neurology, Leopoldina Krankenhaus, Schweinfurt, Germany (Dr Kuhn); Department of Pediatrics, Vestische
Kinderklinik Datteln, University of Witten-Herdecke, Witten, Germany (Dr Niklowitz); and MSE Pharmazeutika
GmbH, Bad Homburg, Germany (Dr Koch).
Correspondence: Alexander Storch, MD, Department of
Neurology, Technical University of Dresden, Fetscherstrasse 74, 01307 Dresden, Germany (Alexander.Storch
@neuro.med.tu-dresden.de).
Author Contributions: Drs Storch and Reichmann had
full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of
the data analysis. Drs Herting and Reichmann contributed equally to this work. Study concept and design: Storch,
Durner, Kuhn, Herting, and Reichmann. Acquisition of
data: Storch, Jost, Vieregge, Spiegel, Greulich, Durner,
Müller, Kupsch, Henningsen, Oertel, Fuchs, Kuhn, and
Herting. Analysis and interpretation of data: Storch, Oertel,
Niklowitz, and Koch. Drafting of the manuscript: Storch
and Müller. Critical revision of the manuscript for important intellectual content: Jost, Vieregge, Spiegel, Greulich,
Durner, Müller, Kupsch, Henningsen, Oertel, Fuchs,
Kuhn, Niklowitz, Koch, Herting, and Reichmann. Statistical analysis: Koch. Obtained funding: Spiegel. Administrative, technical, and material support: Storch,
Vieregge, Spiegel, Durner, Müller, Kupsch, Oertel, and
Herting. Study supervision: Vieregge, Kupsch, Henningsen,
Oertel, Kuhn, Herting, and Reichmann.
Financial Disclosure: None reported.
Funding/Support: This study was supported by a grant
from the Deutsche Parkinson-Vereinigung eV (German
Parkinson Association), Neuss, Germany, and MSE
Pharmazeutika GmbH, Bad Homburg, Germany. The coenzyme Q10 and matching placebo were formulated and
packaged without charge by MSE Pharmazeutika.
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