Study design to assess the effect of opicapone on levodopa pharmacokinetics in different levodopa-optimized treatment regimens in Parkinson's disease patients

Objectives: To assess the feasibility of a multi-site randomised controlled trial to evaluate the effect of functional electrical stimulation on bradykinesia in people with Parkinson’s disease. Design: A two-arm assessor blinded randomised controlled trial with an 18 weeks intervention period and 4 weeks post-intervention follow-up. Setting: Two UK hospitals; a therapy outpatient department in a district general hospital and a specialist neuroscience centre. Participants: A total of 64 participants with idiopathic Parkinson’s disease and slow gait <1.25 ms−1. Interventions: Functional electrical stimulation delivered to the common peroneal nerve while walking in addition to standard care compared with standard care alone. Main measures: Feasibility aims included the determination of sample size, recruitment and retention rates, acceptability of the protocol and confirmation of the primary outcome measure. The outcome measures were 10 m walking speed, Unified Parkinson’s Disease Rating Scale (UPDRS), Mini Balance Evaluation Systems Test, Parkinson’s Disease Questionnaire-39, EuroQol 5-dimension 5-level, New Freezing of Gait questionnaire, Falls Efficacy Score International and falls diary. Participants opinion on the study design and relevance of outcome measures were evaluated using an embedded qualitative study. Results: There was a mean difference between groups of 0.14 ms−1 (CI 0.03, 0.26) at week 18 in favour of the treatment group, which was maintained at week 22, 0.10 ms−1 (CI –0.05, 0.25). There was a mean difference in UPDRS motor examination score of –3.65 (CI –4.35, 0.54) at week 18 which was lost at week 22 –0.91 (CI –2.19, 2.26). Conclusion: The study design and intervention were feasible and supportive for a definitive trial. While both the study protocol and intervention were acceptable, recommendations for modifications are made.

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The Role of α-Synuclein Oligomers in Parkinson’s Disease

International Journal of Molecular Sciences ◽

10.3390/ijms21228645 ◽

2020 ◽

Vol 21 (22) ◽

pp. 8645

Author(s):

Xiao-yu Du ◽

Xi-xiu Xie ◽

Rui-tian Liu

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Theoretical Basis ◽

Critical Role ◽

Treatment Regimens ◽

Propagation Effects ◽

Different Types ◽

Oligomeric Forms ◽

Neurodegeneration Disease

α-synuclein (α-syn) is a protein associated with the pathogenesis of Parkinson’s disease (PD), the second most common neurodegeneration disease with no effective treatment. However, how α-syn drives the pathology of PD remains elusive. Recent studies suggest that α-syn oligomers are the primary cause of neurotoxicity and play a critical role in PD. In this review, we discuss the process of α-syn oligomers formation and the current understanding of the structures of oligomers. We also describe seed and propagation effects of oligomeric forms of α-syn. Then, we summarize the mechanism by which α-syn oligomers exert neurotoxicity and promote neurodegeneration, including mitochondrial dysfunction, endoplasmic reticulum stress, proteostasis dysregulation, synaptic impairment, cell apoptosis and neuroinflammation. Finally, we investigate treatment regimens targeting α-syn oligomers at present. Further research is needed to understand the structure and toxicity mechanism of different types of oligomers, so as to provide theoretical basis for the treatment of PD.

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Differential Expression of Striatal ΔFosB mRNA and FosB mRNA After Different Levodopa Treatment Regimens in a Rat Model of Parkinson’s Disease

Neurotoxicity Research ◽

10.1007/s12640-018-9993-0 ◽

2019 ◽

Vol 35 (3) ◽

pp. 563-574 ◽

Cited By ~ 1

Author(s):

Victoria Palafox-Sanchez ◽

Victoria Sosti ◽

Gabriel Ramirez-García ◽

Jaime Kulisevsky ◽

José Aguilera ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Differential Expression ◽

Rat Model ◽

Treatment Regimens ◽

Levodopa Treatment

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Continuous Subcutaneous Levodopa Delivery for Parkinson’s Disease: A Randomized Study

Journal of Parkinson s Disease ◽

10.3233/jpd-202285 ◽

2020 ◽

pp. 1-10

Author(s):

C. Warren Olanow ◽

Alberto J. Espay ◽

Fabrizio Stocchi ◽

Aaron L. Ellenbogen ◽

Mika Leinonen ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Randomized Study ◽

Preliminary Evidence ◽

Common Adverse Event ◽

Open Label ◽

Open Label Study ◽

Dosing Regimens ◽

Optimized Treatment ◽

Off Time

Background: ND0612 is a continuous, subcutaneous levodopa/carbidopa delivery system in development for patients with Parkinson’s disease (PD) experiencing motor fluctuations Objective: Evaluate the efficacy and safety of two ND0612 dosing regimens in patients with PD. Methods: This was a 28-day open-label study (NCT02577523) in PD patients with ≥2.5 hours/day of OFF time despite optimized treatment. Patients were randomized to treatment with either a 24-hour infusion (levodopa/carbidopa dose of 720/90 mg) or a 14-hour ‘waking-day’ infusion (levodopa/carbidopa dose of 538/68 mg plus a morning oral dose of 150/15 mg). In-clinic assessments of OFF time (primary endpoint) and ON time with or without dyskinesia were determined by a blinded rater over 8 hours (normalized to 16 hours). Results: A total of 38 patients were randomized and 33 (87% ) completed the study. Compared to baseline, OFF time for the overall population was reduced by a least squares (LS) mean[95% CI] of 2.0[– 3.3, – 0.7] hours (p = 0.003). ON time with no/mild dyskinesia was increased from baseline by a LS mean of 3.3[2.0, 4.6] hours (p < 0.0001), and ON time with moderate/severe dyskinesia was reduced by a LS mean of 1.2[– 1.8, – 0.5] hours (p≤0.001). Reduction in OFF time was larger in the 24-hour group (– 2.8[– 4.6, – 0.9] hours; p = 0.004) than in the 14-hour group (– 1.3[– 3.1, 0.5] hours; p = 0.16). Complete resolution of OFF time was observed in 42% (n = 8) of patients in the 24-hour group. Infusion site reactions were the most common adverse event. Conclusion: This study demonstrates the feasibility and safety of continuous subcutaneous delivery of levodopa as a treatment for PD and provides preliminary evidence of efficacy.

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Mapping spontaneous facial expression in people with Parkinson’s disease: A multiple case study design

Cogent Psychology ◽

10.1080/23311908.2017.1376425 ◽

2017 ◽

Vol 4 (1) ◽

pp. 1376425 ◽

Cited By ~ 3

Author(s):

Sarah D. Gunnery ◽

Elena N. Naumova ◽

Marie Saint-Hilaire ◽

Linda Tickle-Degnen ◽

Peter Walla

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Facial Expression ◽

Study Design ◽

Multiple Case Study ◽

Case Study Design ◽

Multiple Case

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2.277 OPTIMIZATION OF PHASE III STUDY DESIGN FOR PIMAVANSERIN IN THE TREATMENT OF PARKINSON'S DISEASE PSYCHOSIS (PDP)

Parkinsonism & Related Disorders ◽

10.1016/s1353-8020(11)70600-9 ◽

2012 ◽

Vol 18 ◽

pp. S134 ◽

Cited By ~ 3

Author(s):

R. Mills ◽

D. Bahr ◽

H. Williams

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Study Design ◽

Phase Iii ◽

Phase Iii Study

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3.020 How the study design influences perceived personality traits changes in Parkinson's disease (PD) after subthalamic deep brain stimulation (DBS-STN)

Parkinsonism & Related Disorders ◽

10.1016/s1353-8020(08)70804-6 ◽

2007 ◽

Vol 13 ◽

pp. S151 ◽

Cited By ~ 3

Author(s):

A. Gronchi-Perrin ◽

S. Aybek ◽

A. Jaques ◽

C. Pollo ◽

P. Burkhard ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Deep Brain Stimulation ◽

Personality Traits ◽

Study Design ◽

Brain Stimulation ◽

Deep Brain

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Prevalence and incidence of Parkinson’s disease and drug-induced parkinsonism in Korea

BMC Public Health ◽

10.1186/s12889-019-7664-6 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 3

Author(s):

Sola Han ◽

Siin Kim ◽

Hyungtae Kim ◽

Hae-Won Shin ◽

Kyoung-Sae Na ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Study Design ◽

Cross Sectional Study ◽

Drug Induced ◽

Cross Sectional ◽

Cohort Study Design ◽

Icd 10 ◽

Incident Cases ◽

Antiparkinsonian Drugs

Abstract Background Parkinson’s disease (PD) and drug-induced parkinsonism (DIP) are the major diseases of parkinsonism. To better understand parkinsonism, we aimed to assess the prevalence and incidence of PD and DIP in Korea from 2012 to 2015. Methods We used the Health Insurance Review and Assessment Service database, which covers the entire population in Korea. We used claims during 2011–2015 to assess epidemiology of PD and DIP during 2012–2015. Retrospective cross-sectional study design was employed to assess prevalence, whereas retrospective cohort study design was used to determine incidence. Patients with at least one claim with ICD-10 G20 and who received antiparkinsonian drugs for at least 60 days were classified as having PD. We excluded patients with antiparkinsonian drugs that can be used for indications other than PD. Patients with at least one claim with ICD-10 G211 or G251 during the prescription period of drugs that are frequently related with DIP were classified as having DIP. Incident cases had a disease-free period of 1 year before diagnosis. To evaluate the significance of changes in the prevalence or incidence over time, Poisson regression was used to determine p for trend. Results The prevalence of PD increased from 156.9 per 100,000 persons in 2012 to 181.3 per 100,000 persons in 2015 (p for trend< 0.0001). The incidence of PD decreased steadily from 35.4 per 100,000 person-years in 2012 to 33.3 per 100,000 person-years in 2015 (p for trend< 0.0001). The prevalence of DIP increased from 7.3 per 100,000 persons in 2012 to 15.4 per 100,000 persons in 2015 (p for trend< 0.0001) and the incidence of DIP increased from 7.1 per 100,000 person-years in 2012 to 13.9 per 100,000 person-years in 2015 (p for trend< 0.0001). Conclusions Our study suggests that the incidence of PD has gradually decreased whereas, the incidence of DIP increased from 2012 to 2015. Further studies are warranted to examine possible causes of increased DIP incidence in order to develop management strategy for parkinsonism.

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