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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Brain Energy Metabolites measured by Magnetic Resonance Spectroscopy
研究概览
简要总结
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.
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Diagnosis of clinically probable PSP (Litvan et al., 1996).
- •Early stage PSP [PSP staging system ≤ III (Golbe, 1997)].
- •Capability and willingness to give written informed consent to participate in the study.
排除标准
- •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, structural brain disease, brain surgery, or electroconvulsive therapy
- •History of stroke related to the onset or progression of PSP symptoms
- •Arterial hypertension (systolic >180 or diastolic >110mm Hg)
- •Thyroid dysfunction requiring thyroxin supplementation (CoQ10 may change its metabolism)
- •Presence of other serious illnesses
- •Insufficient contraception in male and pre-menopausal female participants. Accepted means of contraception are hormonal contraception, intrauterine devices, vaginal rings, preservatives, and abstinence.
- •Pregnancy or lactation period
- •Participation in other drug studies within 60 days before baseline visit.
- •Use of CoQ10 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 modifying mitochondrial activity within 60 days before baseline visit
- •Use of statins within 60 days before baseline visit (inhibit endogenous CoQ10 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 (CoQ10 may change its metabolism).
- •An unstable dosage of CNS-active drugs (e.g. anxiolytics, hypnotics, tranquillizer, and antidepressants) within 30 days before baseline visit or throughout the study.
- •An unstable dosage of other antiparkinsonian drugs within 30 days before baseline visit or throughout the study.
研究组 & 干预措施
Placebo
干预措施: Coenzyme Q10 (Drug)
Coenzyme Q10
干预措施: Coenzyme Q10 (Drug)
结局指标
主要结局
Brain Energy Metabolites measured by Magnetic Resonance Spectroscopy
次要结局
- 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.