Study About Safety and Efficacy of Coenzyme Q10 in Progressive Supranuclear Palsy
Study Details
Study Description
Brief Summary
Study hypothesis:
A 6-week p.o treatment with 5 mg/Kg Coenzyme Q10 is safe and tolerable,increases the brain's metabolism and ameliorates clinical symptoms in patients with PSP.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 2 |
Detailed Description
Background and Rationale:
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Progressive Supranuclear Palsy (PSP, Steele-Richardson-Olszewski Syndrome) is a sporadic neurodegenerative disorder resulting clinically in a Parkinson syndrome (i.e. akinetic-rigid movement disorder) with prominent postural instability, oculomotor deficits, and cognitive decline (for review: Albers and Augood, 2001; Burn and Lees, 2002). With an average annual incidence of 5.3 per 100000 and an age-adjusted prevalence of 6.4 per 100000, PSP is as common as motor-neuron disease (Burn and Lees, 2002). There is no symptomatic treatment, because PSP patients do not respond to any known therapy (Albers and Augood, 2001; Burn and Lees, 2002). The progression of PSP is rapid and the median survival after onset of symptoms is 5-10 years (Albers and Augood, 2001). Presently, there is no known effective symptomatic or neuroprotective therapy for PSP.
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Evidence suggests an impairment of mitochondrial energy metabolism in PSP (Albers and
Beal, 2002):
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Reduced cerebral glucose and ATP metabolism have been shown in functional imaging studies in PSP patients (Forster et al., 1988; Martinelli et al., 2000).
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Cybrid cells harboring mitochondrial genes from PSP patients have decreased ATP-levels and complex I activity (Swerdlow et al., 2000; Albers et al., 2001; Chirichigno et al., 2002).
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A tropical PSP-like tauopathy has been linked clinically and experimentally to the consumption of the fruit and teas of leaves of the tropical plant annona muricata rich in lipophilic complex I inhibitors (Caparros-Lefebvre et al., 1999; 2001). These clinical observations suggest a role for mitochondrial dysfunction in the etiology of PSP.
3.Coenzyme Q10 (CoQ10) is the physiological electron recipient of complex I. Exogenous CoQ10 (1.) enhances the electron transport by complex I and (2.) powerfully scavenges free radicals. Thus, CoQ10 has been shown to reduce the toxicity of complex I inhibitors in vitro (Menke et al., 2003) and in vivo (Beal et al., 1998
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Placebo Comparator: Placebo
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Drug: Coenzyme Q10
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Active Comparator: Coenzyme Q10
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Drug: Coenzyme Q10
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Outcome Measures
Primary Outcome Measures
- Brain Energy Metabolites measured by Magnetic Resonance Spectroscopy []
Secondary Outcome Measures
- Slowdown of clinical progression after 6 weeks, rated with UPDRS III, PSP rating scale, PSP staging system, modified Hoehn and Yahr, FAB, MMSE, Montgomery- Asberg Depression scale, Schwab and England Score and UPDRS II []
- Safety and tolerability:Vital signs physical examination and safety laboratory with Blood tests and urine status. []
- Evaluation of occuring adverse events(AE), severe adverse events(SAE) up to 6 Weeks after the beginning of the treatment. []
Eligibility Criteria
Criteria
Inclusion Criteria:
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Diagnosis of clinically probable PSP (Litvan et al., 1996).
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Early stage PSP [PSP staging system ≤ III (Golbe, 1997)].
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Capability and willingness to give written informed consent to participate in the study.
Exclusion Criteria:
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Age > 85 years.
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Parkinson syndromes other than PSP (e.g. idiopathic Parkinson's disease, multiple system atrophy, diffuse Lewy body disease, FTDP17, symptomatic parkinsonism)
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Dementia [Mini Mental State Examination (MMSE) ≤ 24]
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History of epilepsy, structural brain disease, brain surgery, or electroconvulsive therapy
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History of stroke related to the onset or progression of PSP symptoms
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Arterial hypertension (systolic >180 or diastolic >110mm Hg)
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Thyroid dysfunction requiring thyroxin supplementation (CoQ10 may change its metabolism)
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Presence of other serious illnesses
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Insufficient contraception in male and pre-menopausal female participants. Accepted means of contraception are hormonal contraception, intrauterine devices, vaginal rings, preservatives, and abstinence.
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Pregnancy or lactation period
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Participation in other drug studies within 60 days before baseline visit.
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Use of CoQ10 within 60 days before baseline visit
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Use of any antioxidants (e.g. vitamin E, C) within 60 days before baseline visit
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Use of any drugs modifying mitochondrial activity within 60 days before baseline visit
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Use of statins within 60 days before baseline visit (inhibit endogenous CoQ10 production)
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Use of drugs interfering with catecholamine metabolism (e.g. reserpine, amphetamines, or monaomine oxidase-A inhibitors, methylphenidate, cinnarizine) within 30 days before baseline visit.
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Use of Levodopa within 30 days before baseline visit (CoQ10 may change its metabolism).
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An unstable dosage of CNS-active drugs (e.g. anxiolytics, hypnotics, tranquillizer, and antidepressants) within 30 days before baseline visit or throughout the study.
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An unstable dosage of other antiparkinsonian drugs within 30 days before baseline visit or throughout the study.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Neurologische Klinik der Philipps-Universität Marburg | Marburg | Hessen | Germany | 35033 |
Sponsors and Collaborators
- German Parkinson Study Group (GPS)
- MSE Pharmazeutika GmbH, Louisenstr.114D-61348 Bad Homburg, Germany
- Pitzer Stiftung
- Philipps University Marburg Medical Center
Investigators
- Principal Investigator: Wolfgang Oertel, Professor, Neurologische Klinik der Philipps Universität Marburg
Study Documents (Full-Text)
None provided.More Information
Additional Information:
- Homepage Competence Network on Parkinson's disease sponsored by the German government, Language German, English
- Homepage Coordination Center for Clinical Studies to MEMSA Study, Language: German
Publications
None provided.- EudraCT: 2005-000574-40