Study About Safety and Efficacy of Coenzyme Q10 in Progressive Supranuclear Palsy
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Mono-Center, Prospective, Double-Blind, Placebo-Controlled, Randomized Clinical Phase IIa Trial to Assess the Safety, Tolerability, and Immediate Biological Effects of Coenzyme Q10 - nanoQuinon® in Progressive Supranuclear Palsy|
- Brain Energy Metabolites measured by Magnetic Resonance Spectroscopy
- 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.
|Study Start Date:||May 2006|
|Study Completion Date:||February 2007|
Background and Rationale:
1. 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.
2. Evidence suggests an impairment of mitochondrial energy metabolism in PSP (Albers and Beal, 2002):
- Reduced cerebral glucose and ATP metabolism have been shown in functional imaging studies in PSP patients (Forster et al., 1988; Martinelli et al., 2000).
- 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).
- 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
|Neurologische Klinik der Philipps-Universität Marburg|
|Marburg, Hessen, Germany, 35033|
|Principal Investigator:||Wolfgang Oertel, Professor||Neurologische Klinik der Philipps Universität Marburg|