Brain Energy Metabolism in Progressive Supranuclear Palsy: Comparison of PSP Patients and Healthy Controls and Effect of Coenzyme Q10 – nanoQuinon® - N/A

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2005-000574-40-DE
• Date of registration: 24/01/2006
• Prospective Registration: Yes
• Primary sponsor: Kompetenznetz Parkinson e.V.
• Public title: Brain Energy Metabolism in Progressive Supranuclear Palsy: Comparison of PSP Patients and Healthy Controls and Effect of Coenzyme Q10 – nanoQuinon® - N/A
• Scientific title: Brain Energy Metabolism in Progressive Supranuclear Palsy: Comparison of PSP Patients and Healthy Controls and Effect of Coenzyme Q10 – nanoQuinon® - N/A
• Date of first enrolment: 24/04/2006
• Target sample size: 30
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-000574-40
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Germany

Key inclusion & exclusion criteria

Inclusion criteria:
· Subjects have a diagnosis of clinically probable PSP
· Subjects have early stage PSP: PSP staging system = III
· Subjects are capable and willing to give written 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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
· Age > 85 years.
· Parkinson syndromes other than PSP (e.g. idiopathic Parkinson‘s disease, multiple system atrophy, diffuse Lewy body disease, FTDP17, symptomatic parkinsonism)
· Dementia [Mini Mental State Examination (MMSE) = 24]
· History of epilepsy, stroke, structural brain disease, brain surgery, or electroconvulsive therapy
· Arterial hypertension (systolic >180 or diastolic >110mm Hg)
· Diagnosis of systemic disorders affecting the metabolism or function of the brain (e.g. diabetes mellitus) unless sufficiently treated.
· Presence of other serious illnesses
· Insufficient contraception in male and pre-menopausal female participants.
· Participation in other drug studies within 30 days before baseline visit.
· Use of coenzyme Q10 within 60 days before baseline visit
· Use of any antioxidants (e.g. vitamin E, C) within 60 days before baseline visit
· Use of any drugs interfering with mitochondrial activity within 60 days before baseline visit
· Use of statins within 60 days before baseline visit (inhibit endogenous coenzyme Q10 production)
· Use of drugs interfering with catecholamine metabolism (e.g. reserpine, amphetamines, or monaomine oxidase-A inhibitors, methylphenidate, cinnarizine) within 30 days before baseline visit.
· Use of Levodopa within 30 days before baseline visit (coenzyme Q10 may change its metabolism).
· An unstable dosage of CNS-active drugs (e.g. anxiolytics, hypnotics, tranquillizer, antidepressants) within 30 days before baseline visit.
· An unstable dosage of other antiparkinsonian drugs within 30 days before baseline visit.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

PSP is a sporadic neurodegenerative disorder resulting in a Parkinson syndrome with postural instability, oculomotor deficits, and cognitive decline. With an average annual incidence of 5.3 / 100000 and an age-adjusted prevalence of 6.4 / 100000, PSP is as common as motor-neuron disease. The progression of PSP is rapid and the median survival after onset of symptoms is 5-10 years. Presently, there is no known effective symptomatic or neuroprotective therapy for PSP.

Intervention(s)

Product Name: Coenzym Q10 Nanodispersion
Product Code: ASK Nr. 21972
Pharmaceutical Form: Oral drops*
INN or Proposed INN: Ubidecarenon
CAS Number: 303-98-0
Current Sponsor code: Sanomit
Other descriptive name: Coenzym Q10, Ubiquinon, Ubichinon
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: range
Concentration number: 47.5-52.5
Pharmaceutical form of the placebo: Oral drops*
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: The level of ADP measured by Magnetic Resonance (MR-) Spectroscopy will be compared in the frontal cortex and putamen in
- healthy control persons vs. PSP patients and
- PSP patients prior to and after 6 weeks of treatment with CoQ10.

Primary end point(s): The primary goal of this study is to investigate whether the amount of adenosine-diphosphate in cells of the frontal cortex and putamen differ between PSP patients and healthy controls. The problem will be formulated statistically as a two-sided test of the hypothesis (H0: “Equal distribution of the the amount of adenosine-diphosphate in cells of the frontal cortex and putamen in the two groups”). Due to the small sample size the Wilcoxon-Mann-Whitney-test will be used. The significance level is set to a = 0.05.

Intent-to-treat (ITT) population All PSP patients randomized.
Per-protocol (PP) population All PSP patients of the ITT population with completed treatment according to the study plan and no major protocol violations.
Safety (S) population All PSP patients randomized who received at least one administration of study medication.
MRS population All PSP patients and healthy control subjects having undergone baseline MRS assessment.
The test of the primary endpoint (i.e test of H0) will be applied to the MRS population. To examine the robustness of its result, a further test in the FS population with appropriate imputation of missing values will be done.

In order to obtain evidence for the assumed pathophysiological mechanisms (cf. 2.2), descriptive statistics (mean, median, standard deviation, range, quantiles and 95% confidence intervals) for the parameters measured by MR spectroscopy (total amounts of ATP, ADP, pCre, tCre, Lac, ratio of ADP to ATP, ratio of pCre to tCre; cf 3.2) will be given for the baseline values in the subgroup of non-PSP subjects and the subgroup of PSP patients. These analyses will be done for the MRS population.

To obtain evidence for the effect of CoQ10 on these mechanisms descriptive statistics for differences from baseline to the 6 weeks visit in the aforementioned parameters will be given for the subgroup of PSP patients for each treatment group (CoQ10 and placebo). These analyses will be done for the ITT population and for the PP population in order to examine the robustness of results.

Analysis of all secondary endpoints takes place exploratively and descriptively. For categorical variables, the number and proportion of patients in each category will be given. For continuous variables, the number of patients, mean, standard deviation, quartiles, range and 95% confidence intervals will be provided. The data will be summarized for all patients as well as for each of the randomized treatment groups

Analysis of safety takes place for the S population.

Secondary Objective: 1.
Further parameters of brain energy metabolism [ATP, phosphorylated creatinine (pCre), the total amount of creatinine (tCre), inorganic Phosphate (Pi), lactate (Lac)] as assessed by Magnetic Resonance (MR-) Spectroscopy (Comparison of controls to PSP patients and comparison of PSP patients prior to and after 6 weeks of treatment with CoQ10 or Placebo).

2.
Disease severity: Comparison of PSP patients prior to and after 6 weeks of treatment with CoQ10 or placebo.
-Movement disorder: UPDRS III PSP rating scale, PSP staging system, H&Y.
-Cognition: Frontal Assessment Battery , Mini Mental State Examination, Montgomery-Åsberg scale.
-Activities of daily living: Schwab and England score, UPDRS II.

3.
Safety and tolerability:
-Vital signs and physical examination, Blood tests , urine status, Adverse events and serious adverse events.

4.
Levels of reduced / oxidized coenzyme Q 10 in serum: Comparison in PSP patients prior to and after 6 weeks of treatment with CoQ10

Secondary ID(s)

PSP-CoQ10