Randomized, double-blind, placebo-controlled pilot trial of reduced coenzyme Q10 for Parkinson's disease

Yoritaka, Asako; Kawajiri, Sumihiro; Yamamoto, Yorihiro; Nakahara, Toshiki; Ando, Maya; Hashimoto, Kazuhiko; Nagase, Midori; Saito, Yutaro; Hattori, Nobutaka

doi:10.1016/j.parkreldis.2015.05.022

Cited by 71 publications

(40 citation statements)

References 29 publications

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“…It has been demonstrated that, in mice, CoQ10 can protect against striatal lesions produced by the mitochondrial toxins malonate and 3-nitropropionic acid and it also protects against 1-methyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity [50,59,60]. Some studies [55,56,61,62] have shown beneficial effect s of oral CoQ10 supplementation in Parkinson's patients, while in other studies [63,64] CoQ10 showed no evidence of clinical benefit. However, a recent review [65] has established that the supplementation with CoQ10 does not slow functional decline nor provide any symptomatic benefit for patients with Parkinson's disease; moreover, data from a subsequent meta-analysis of randomized controlled trials [66] performed to assess the efficacy of CoQ10 supplementation in the treatment of Parkinson's disease, have confirmed that CoQ10 is not superior to placebo in terms of motor symptoms, although it has been shown safe and well tolerated.…”

Section: Discussionmentioning

confidence: 99%

Coenzyme Q10 deficiency in elderly: Can nutritional supplementation play a role? Mini review

Carella¹,

Marinelli²,

Pumpo³

et al. 2019

The European Research Journal

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Coenzyme Q10 (CoQ10), an important mitochondrial redox component, plays a pivotal role in cellular energy production; moreover, it is the only lipid-soluble antioxidant endogenously synthesized in humans. Given its function and physiological importance, it is not surprising that CoQ10 deficiency may result in several diseases. With aging, humans begin to lose the ability to synthesize CoQ10 from food, resulting in reduced serum levels of CoQ10 and contributing to aging-associated symptoms. Poor eating habits, infections, stress and also some drugs, as beta blockers, antihypertensive agents and statins, may reduce serum levels of CoQ10. Dietary supplementation has been proposed as key strategy to increase CoQ10 availability, improving health status in elderly; however CoQ10 is not approved by U.S. Food and Drug Administration for the treatment of any medical condition and it is sold only as a dietary supplement. Aim of the study was to examine the latest relevant evidences on potential benefits of CoQ10 nutritional supplement and its implication in improving health status in elderly. There is evidence that, in elderly, oral administration of CoQ10 reduces oxidative stress and inflammatory markers and reduces cardiovascular mortality; in diabetics CoQ10 treatment improves insulin sensitivity and decreases glycated hemoglobin. Therapeutic benefit from CoQ10 supplementation has also been obtained in neurodegenerative diseases as Parkinson's, Alzheimer's and Huntington's diseases. CoQ10 supplements could be useful in several aging-related clinical conditions; however, well standardized longterm and larger further studies are needed

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Section: Discussionmentioning

confidence: 99%

Coenzyme Q10 deficiency in elderly: Can nutritional supplementation play a role? Mini review

Carella¹,

Marinelli²,

Pumpo³

et al. 2019

The European Research Journal

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“…Based on the evidence, a number of pharmacological agents that might improve mitochondrial function or reduce oxidative stress have been developed to attempt to modify the disease course [27, 28], and a few of them, such as inosine (a precursor of urate) and the reduced form of CoQ 10 , have shown possible therapeutic effects in patients with PD [29, 30]. The increase in dopaminergic neuronal oxidative stress caused by mitochondrial dysfunction presented here suggests that therapeutic molecules targeting these pathogenic mechanisms would be able to slow the disease progression even in the advanced stage.…”

Section: Discussionmentioning

confidence: 99%

Precise Evaluation of Striatal Oxidative Stress Corrected for Severity of Dopaminergic Neuronal Degeneration in Patients with Parkinson’s Disease: A Study with <sup>62</sup>Cu-ATSM PET and <sup>123</sup>I-FP-CIT SPECT

et al. 2017

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Background: This study sought to precisely evaluate striatal oxidative stress and its relationship with the disease severity in Parkinson’s disease (PD) using double brain imaging, ⁶²Cu-diacetyl-bis (N⁴-methylthiosemicarbazone) (⁶²Cu-ATSM) PET and ¹²³I-FP-CIT SPECT. Methods: Nine PD patients were studied with brain ⁶²Cu-ATSM PET for oxidative stress and ¹²³I-FP-CIT SPECT for the density of striatal dopamine transporter. Standardized uptake values (SUVs) were obtained from the delayed phase of dynamic ⁶²Cu-ATSM PET, and striatum-to-cerebellum SUV ratio (SUVR) was calculated. To correct the effect of neuronal loss in the striatum, ⁶²Cu-ATSM SUVR was corrected for striatal specific binding ratio (SBR) values of ¹²³I-FP-CIT (SUVR/SBR). Results: ⁶²Cu-ATSM SUVR without correction was not significantly correlated with disease severity estimated by the Unified Parkinson’s Disease Rating Scale (UPDRS) scores or ¹²³I-FP-CIT SBR. In contrast, the SUVR/SBR showed significant correlations with the UPDRS total and motor scores, and ¹²³I-FP-CIT SBR. Conclusion: Oxidative stress in the remaining striatal dopaminergic neurons estimated by SUVR/SBR was increased with disease severity in PD patients, suggesting that oxidative stress based on mitochondrial dysfunction contributes to promoting dopaminergic neuronal degeneration in PD. ⁶²Cu-ATSM PET with ¹²³I-FP-CIT SPECT correction would be a promising tool to evaluate dopaminergic neuronal oxidative stress in PD.

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“…Any beneficial effect at later disease stages, where different neurological systems are starting to be involved, would be missed by such a design and exploration of these drugs for PD are most likely going to be stopped after a negative result in an early disease group. In fact, one phase II trial of coenzyme Q10 stratified patients into early (not treated with levodopa) and more advanced (PD with wearing off) arms and found a treatment benefit (change in total UPDRS score) only in more advanced disease [85]. Although this result came from a very small study (average of 12 patients per arm) and may represent the differential sensitivity of the scale at these two disease stages, a potential beneficial effect in this patient group could not have been (and was not) captured in the later phase III trial that focused on early, untreated disease [19].…”

Section: Challenge 3: Trial Design Inclusion Criteriamentioning

confidence: 99%

Is It Possible to Conduct a Multi-Arm Multi-Stage Platform Trial in Parkinson’s Disease: Lessons Learned from Other Neurodegenerative Disorders and Cancer

Zeissler

Parmar

et al. 2020

JPD

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Many potential disease modifying therapies have been identified as suitable for clinical evaluation in Parkinson's disease (PD). Currently, the evaluation of compounds in phase II and phase III clinical trials in PD are set up in isolation, a process that is lengthy, costly and lacks efficiency. This review will introduce the concept of a multi-arm, multi-stage (MAMS) trial platform which allows for the assessment of several potential therapies at once, transitioning seamlessly from a phase II safety and efficacy study to a phase III trial by means of an interim analysis. At the interim checkpoint, ineffective arms are dropped and replaced by new treatment arms, thereby allowing for the continuous evaluation of interventions. MAMS trial platforms already exist for prostate, renal and oropharyngeal cancer and are currently being developed for progressive multiple sclerosis (PMS) and motor neuron disease (MND) within the UK. As a MAMS trial will evaluate many potential treatments it is of critical importance that a widely endorsed core protocol is developed which will investigate outcomes and objectives meaningful to patients. This review will discuss the challenges of drug selection, trial design, stratification and outcome measures and will share strategies implemented in the planned MAMS trials for MND and PMS that may be of interest to the PD field.

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Randomized, double-blind, placebo-controlled pilot trial of reduced coenzyme Q10 for Parkinson's disease

Cited by 71 publications

References 29 publications

Coenzyme Q10 deficiency in elderly: Can nutritional supplementation play a role? Mini review

Coenzyme Q10 deficiency in elderly: Can nutritional supplementation play a role? Mini review

Precise Evaluation of Striatal Oxidative Stress Corrected for Severity of Dopaminergic Neuronal Degeneration in Patients with Parkinson’s Disease: A Study with <sup>62</sup>Cu-ATSM PET and <sup>123</sup>I-FP-CIT SPECT

Is It Possible to Conduct a Multi-Arm Multi-Stage Platform Trial in Parkinson’s Disease: Lessons Learned from Other Neurodegenerative Disorders and Cancer

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