scholarly journals PF-06649751 efficacy and safety in early Parkinson’s disease: a randomized, placebo-controlled trial

2020 ◽  
Vol 13 ◽  
pp. 175628642091129 ◽  
Author(s):  
Robert Riesenberg ◽  
John Werth ◽  
Yao Zhang ◽  
Sridhar Duvvuri ◽  
David Gray
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rating Scale ◽  
Early Stage ◽  
Partial Agonist ◽  
Controlled Trial ◽  
Controlled Clinical Trial ◽  
Motor Symptoms ◽  
Efficacy And Safety ◽  
Updrs Part

Background: PF-06649751 is a novel, oral, non-catechol-based, D1/D5 dopamine receptor partial agonist under investigation for the treatment of motor symptoms associated with Parkinson’s disease. Methods: A 15-week, phase II, double-blind, placebo-controlled clinical trial was conducted to assess the efficacy and safety of flexible-dose PF-06649751 in subjects with early stage Parkinson’s disease (ClinicalTrials.gov identifier: NCT02847650). Results: Enrollment was terminated early for reasons unrelated to the trial. Overall, 57 subjects received study medication (PF-06649751 = 29; placebo = 28) and 47 completed the study (PF-06649751 = 25; placebo = 22). Despite early termination, the study met its primary endpoint with the PF-06649751 group showing statistically significant improvement from baseline in the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III score at week 15 compared with placebo. Mean (SE) change in MDS-UPDRS Part III score was −9.0 (1.54) for PF-06649751 and −4.3 (1.65) for placebo. This corresponds to an improvement versus placebo of 4.8 for the PF-06649751 group (two-sided p = 0.0407; 90% CI = 1.0, 8.6). Statistically significant improvement in MDS-UPDRS-III score was also observed at all assessment time points prior to week 15. The safety profile of PF-06649751 was similar to that observed in prior studies, with the majority of adverse events (AEs) reported as mild or moderate. The most common AEs in the PF-06649751 group were nausea, headache, dry mouth, somnolence, and tremor. Conclusions: Once-daily dosing of oral PF-06649751 resulted in significant improvement of motor symptoms and was generally well tolerated in subjects with early stage Parkinson’s disease.

scholarly journals Boxing vs Sensory Exercise for Parkinson’s Disease: A Double-Blinded Randomized Controlled Trial

2021 ◽  
pp. 154596832110231
Author(s):  
Kishoree Sangarapillai ◽  
Benjamin M. Norman ◽  
Quincy J. Almeida
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Randomized Controlled Trial ◽  
Repeated Measures ◽  
Rating Scale ◽  
Controlled Trial ◽  
Motor Symptoms ◽  
Post Intervention ◽  
Randomized Controlled ◽  
Double Blinded

Background. Exercise is increasingly becoming recognized as an important adjunct to medications in the clinical management of Parkinson’s disease (PD). Boxing and sensory exercise have shown immediate benefits, but whether they continue beyond program completion is unknown. This study aimed to investigate the effects of boxing and sensory training on motor symptoms of PD, and whether these benefits remain upon completion of the intervention. Methods. In this 20-week double-blinded randomized controlled trial, 40 participants with idiopathic PD were randomized into 2 treatment groups, (n = 20) boxing or (n = 20) sensory exercise. Participants completed 10 weeks of intervention. Motor symptoms were assessed at (week 0, 10, and 20) using the Unified Parkinson’s Disease Rating Scale (UPDRS-III). Data were analyzed using SPSS, and repeated-measures ANOVA was conducted. Results. A significant interaction effect between groups and time were observed F(1, 39) = 4.566, P = .036, where the sensory group improved in comparison to the boxing group. Post hoc analysis revealed that in comparison to boxing, the effects of exercise did not wear off at washout (week 20) P < .006. Conclusion. Future rehabilitation research should incorporate similar measures to explore whether effects of exercise wear off post intervention.

scholarly journals The Add-On Effect of Lactobacillus plantarum PS128 in Patients With Parkinson's Disease: A Pilot Study

2021 ◽  
Vol 8 ◽  
Author(s):  
Chin-Song Lu ◽  
Hsiu-Chen Chang ◽  
Yi-Hsin Weng ◽  
Chiung-Chu Chen ◽  
Yi-Shan Kuo ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Lactobacillus Plantarum ◽  
Outcome Measures ◽  
Rating Scale ◽  
Controlled Trial ◽  
Secondary Outcome ◽  
Motor Deficits ◽  
Motor Symptoms ◽  
Non Motor Symptoms

Background:Lactobacillus plantarum PS128 (PS128) is a specific probiotic, known as a psychobiotic, which has been demonstrated to alleviate motor deficits and inhibit neurodegenerative processes in Parkinson's disease (PD)-model mice. We hypothesize that it may also be beneficial to patients with PD based on the possible mechanism via the microbiome-gut-brain axis.Methods: This is an open-label, single-arm, baseline-controlled trial. The eligible participants were scheduled to take 60 billion colony-forming units of PS128 once per night for 12 weeks. Clinical assessments were conducted using the Unified Parkinson's Disease Rating Scale (UPDRS), modified Hoehn and Yahr scale, and change in patient “ON-OFF” diary recording as primary outcome measures. The non-motor symptoms questionnaire, Beck depression inventory-II, patient assessment of constipation symptom, 39-item Parkinson's Disease Questionnaire (PDQ-39), and Patient Global Impression of Change (PGI-C) were assessed as secondary outcome measures.Results: Twenty-five eligible patients (32% women) completed the study. The mean age was 61.84 ± 5.74 years (range, 52–72), mean disease duration was 10.12 ± 2.3 years (range, 5–14), and levodopa equivalent daily dosage was 1063.4 ± 209.5 mg/daily (range, 675–1,560). All patients remained on the same dosage of anti-parkinsonian and other drugs throughout the study. After 12 weeks of PS128 supplementation, the UPDRS motor scores improved significantly in both the OFF and ON states (p = 0.004 and p = 0.007, respectively). In addition, PS128 intervention significantly improved the duration of the ON period and OFF period as well as PDQ-39 values. However, no obvious effect of PS128 on non-motor symptoms of patients with PD was observed. Notably, the PGI-C scores improved in 17 patients (68%). PS128 intervention was also found to significantly reduce plasma myeloperoxidase and urine creatinine levels.Conclusion: The present study demonstrated that PS128 supplementation for 12 weeks with constant anti-parkinsonian medication improved the UPDRS motor score and quality of life of PD patients. We suggest that PS128 could serve as a therapeutic adjuvant for the treatment of PD. In the future, placebo-controlled studies are needed to further support the efficacy of PS128 supplementation.Clinical Trial Registration:https://clinicaltrials.gov/, identifier: NCT04389762.

scholarly journals Baseline prevalence and longitudinal evolution of non-motor symptoms in early Parkinson’s disease: the PPMI cohort

2017 ◽  
Vol 89 (1) ◽  
pp. 78-88 ◽  
Author(s):  
Tanya Simuni ◽  
Chelsea Caspell-Garcia ◽  
Christopher S Coffey ◽  
Daniel Weintraub ◽  
Brit Mollenhauer ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rating Scale ◽  
De Novo ◽  
Controlled Study ◽  
Motor Symptoms ◽  
Biological Variables ◽  
Significant Difference ◽  
Non Motor Symptoms ◽  
Updrs Part

ObjectiveTo examine the baseline prevalence and longitudinal evolution in non-motor symptoms (NMS) in a prospective cohort of, at baseline, patients with de novo Parkinson’s disease (PD) compared with healthy controls (HC).MethodsParkinson’s Progression Markers Initiative (PPMI) is a longitudinal, ongoing, controlled study of de novo PD participants and HC. NMS were rated using the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part I score and other validated NMS scales at baseline and after 2 years. Biological variables included cerebrospinal fluid (CSF) markers and dopamine transporter imaging.Results423 PD subjects and 196 HC were enrolled and followed for 2 years. MDS-UPDRS Part I total mean (SD) scores increased from baseline 5.6 (4.1) to 7.7 (5.0) at year 2 in PD subjects (p<0.001) versus from 2.9 (3.0) to 3.2 (3.0) in HC (p=0.38), with a significant difference between the groups (p<0.001). In the multivariate analysis, higher baseline NMS score was associated with female sex (p=0.008), higher baseline MDS-UPDRS Part II scores (p<0.001) and more severe motor phenotype (p=0.007). Longitudinal increase in NMS severity was associated with the older age (0.008) and lower CSF Aβ1–42 (0.005) at baseline. There was no association with the dose or class of dopaminergic therapy.ConclusionsThis study of NMS in early PD identified clinical and biological variables associated with both baseline burden and predictors of progression. The association of a greater longitudinal increase in NMS with lower baseline Aβ1–42 level is an important finding that will have to be replicated in other cohorts.Trial registrationClinicalTrials.gov identifier: NCT01141023.

scholarly journals The Effects of Long-Term 40-Hz Physioacoustic Vibrations on Motor Impairments in Parkinson’s Disease: A Double-Blinded Randomized Control Trial

Healthcare ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 113
Author(s):  
Abdullah Mosabbir ◽  
Quincy J. Almeida ◽  
Heidi Ahonen
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rating Scale ◽  
Controlled Trial ◽  
Motor Symptom ◽  
Therapeutic Effects ◽  
Motor Symptoms ◽  
Quantitative Evidence ◽  
40 Hz

Recent studies have suggested that vibration therapy may have a positive influence in treating motor symptoms of Parkinson’s disease (PD). However, quantitative evidence of the benefits of vibration utilized inconsistent methods of vibration delivery, and to date there have been no studies showing a long-term benefit of 40 Hz vibration in the PD population. The objective of this study was to demonstrate the efficacy of vibration administered via a physioacoustic therapy method (PAT) on motor symptoms of PD over a longer term, completed as a randomized placebo-controlled trial. Overall motor symptom severity measured by the Unified Parkinson’s Disease Rating Scale III showed significant improvements in the treatment group over 12 weeks. Specifically, all aspects of PD, including tremor, rigidity, bradykinesia, and posture and gait measures improved. To our knowledge, this is the first study to quantitatively assess 40-Hz vibration applied using the PAT method for potential long-term therapeutic effects on motor symptoms of PD.

scholarly journals Longitudinal evolution of non-motor symptoms in early Parkinson’s disease: a 3-year prospective cohort study

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Ruwei Ou ◽  
Yanbing Hou ◽  
Qianqian Wei ◽  
Junyu Lin ◽  
Kuncheng Liu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Effect Size ◽  
Rating Scale ◽  
Early Stage ◽  
Chinese Patients ◽  
Sexual Dysfunctions ◽  
Motor Symptoms ◽  
Small Effect Size ◽  
Non Motor Symptoms

AbstractThe progression of global non-motor symptoms (NMS) in Chinese patients with Parkinson’s disease (PD) has not been explored. We aimed to examine the longitudinal evolution of overall NMS in a 3-year prospective Chinese cohort with early-stage PD. We included 224 patients with early PD who underwent annual evaluation of motor and non-motor symptoms. NMS was assessed using the non-motor symptoms scale (NMSS). We observed an increased number of NMS in the majority of the NMSS domains except mood/apathy and sexual dysfunctions. Significant deterioration was observed in the sleep/fatigue, perceptual problems/hallucinations, attention/memory, gastrointestinal, urinary, and miscellaneous domains during the follow-up (P < 0.05). Notably, the number and the score of sexual dysfunctions decreased with the progression of the disease. All NMSS domains showed a small effect size from baseline to 1-, 2-, and 3-year follow-ups (effect size < 0.5). The generalized estimating equations model indicated that the total number of NMS was significantly associated with age and the Unified Parkinson’s Disease Rating Scale (UPDRS) III score (P < 0.05). Multiple logistic regression indicated that a high number of NMS at baseline was associated with a 3-point, a 6-point, and a 9-point increase in the UPDRS III score from baseline to 1-year (odds ratio [OR] 1.074, P = 0.017), 2-year (OR 1.113, P = 0.001), and 3-year (OR 1.117, P < 0.001), respectively. Our study indicated that overall NMS evolution in early PD is mild and multidimensional; a high NMS burden in early PD predicts the faster motor progression of PD. Our study is helpful for understanding the longitudinal evolution of NMS in PD.

scholarly journals The Effect of Rotigotine on Cognitive Function and Sleep Problems in Parkinson's Disease: an Open-Label Pilot Study

2021 ◽  
Author(s):  
Keisuke Suzuki ◽  
Kei Funakoshi ◽  
Hiroaki Fujita ◽  
Koichi Hirata
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Function ◽  
Daytime Sleepiness ◽  
Sleep Disturbances ◽  
Rating Scale ◽  
Sleep Problems ◽  
Motor Symptoms ◽  
Open Label ◽  
Updrs Part

Abstract Background: We hypothesized that rotigotine may have a positive effect on cognitive function in patients with Parkinson’s disease (PD) by improving daytime motor function and nighttime sleep status due to its 24-hour sustained properties.Methods: We evaluated the effect of rotigotine on motor symptoms, cognitive function, daytime sleepiness, sleep disturbances, and motor symptoms in 10 PD patients with sleep disturbances, defined as a PD Sleep Scale (PDSS)-2 score of ≥ 15, in a single-center, 3-month open-label study. Participants received 24 mg/24 h (patch content: 4.5-9 mg) rotigotine for a 3-month period. At baseline and 3 months, patients were evaluated on the Movement Disorder Society Revision of the Unified PD Rating Scale (MDS-UPDRS) parts III and IV and cognitive assessments, such as the Mini-Mental State Examination (MMSE), frontal assessment battery (FAB) and Montreal Cognitive Assessment (MoCA). The Epworth Sleepiness Scale (ESS) and PDSS-2 were administered at baseline and at 1 month, 2 months and 3 months.Results: At 3 months, MDS-UPDRS part III (-10.7, p<0.001) and MDS-UPDRS part IV (-1.0, p=0.023) scores significantly decreased, MoCA scores (1.7, p=0.0095) significantly increased, and off time significantly decreased (-43.0 min; p=0.029) from baseline. PDSS-2 scores significantly decreased from baseline at 2 months (-14.5, p<0.05) and 3 months (-20.0, p<0.001). ESS, MMSE or FAB scores did not significantly change after rotigotine treatment.Conclusion: Our preliminary findings suggest that low-dose rotigotine could improve motor symptoms, sleep disturbance, and cognitive function without worsening daytime sleepiness in patients with PD.

scholarly journals Motor Progression in Early-Stage Parkinson's Disease: A Clinical Prediction Model and the Role of Cerebrospinal Fluid Biomarkers

2021 ◽  
Vol 12 ◽  
Author(s):  
Ling-Yan Ma ◽  
Yu Tian ◽  
Chang-Rong Pan ◽  
Zhong-Lue Chen ◽  
Yun Ling ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dynamic Models ◽  
Rating Scale ◽  
Early Stage ◽  
Neurovascular Unit ◽  
Progression Model ◽  
Progression Markers ◽  
Updrs Part ◽  
Threshold Range

Background: The substantial heterogeneity of clinical symptoms and lack of reliable progression markers in Parkinson's disease (PD) present a major challenge in predicting accurate progression and prognoses. Increasing evidence indicates that each component of the neurovascular unit (NVU) and blood-brain barrier (BBB) disruption may take part in many neurodegenerative diseases. Since some portions of CSF are eliminated along the neurovascular unit and across the BBB, disturbing the pathways may result in changes of these substances.Methods: Four hundred seventy-four participants from the Parkinson's Progression Markers Initiative (PPMI) study (NCT01141023) were included in the study. Thirty-six initial features, including general information, brief clinical characteristics and the current year's classical scale scores, were used to build five regression models to predict PD motor progression represented by the coming year's Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III score after redundancy removal and recursive feature elimination (RFE)-based feature selection. Then, a threshold range was added to the predicted value for more convenient model application. Finally, we evaluated the CSF and blood biomarkers' influence on the disease progression model.Results: Eight hundred forty-nine cases were included in the study. The adjusted R2 values of three different categories of regression model, linear, Bayesian and ensemble, all reached 0.75. Models of the same category shared similar feature combinations. The common features selected among the categories were the MDS-UPDRS Part III score, Montreal Cognitive Assessment (MOCA) and Rapid Eye Movement Sleep Behavior Disorder Questionnaire (RBDSQ) score. It can be seen more intuitively that the model can achieve certain prediction effect through threshold range. Biomarkers had no significant impact on the progression model within the data in the study.Conclusions: By using machine learning and routinely gathered assessments from the current year, we developed multiple dynamic models to predict the following year's motor progression in the early stage of PD. These methods will allow clinicians to tailor medical management to the individual and identify at-risk patients for future clinical trials examining disease-modifying therapies.

A Dual Centre Study of Pain in Parkinson’s Disease and Its Relationship with Other Non-Motor Symptoms

2020 ◽  
Vol 10 (4) ◽  
pp. 1817-1825
Author(s):  
Pritha Ghosh ◽  
Paola Imbriani ◽  
Nicoletta Caputi ◽  
Silvia Natoli ◽  
Tommaso Schirinzi ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rating Scale ◽  
Clustering Algorithms ◽  
Motor Symptom ◽  
Sleep Disruption ◽  
Motor Symptoms ◽  
Cross Sectional ◽  
Non Motor Symptoms ◽  
Updrs Part

Background: Pain is a disabling and often underestimated non-motor symptom (NMS) detrimentally affecting the quality of life of patients with Parkinson’s disease (PD). Objective: Here, we conducted a cross-sectional, observational international study on 167 patients with idiopathic PD in order to analyze the potential relationship between pain and other NMS. Methods: Subjects were assessed with the Unified Parkinson’s Disease Rating Scale (UPDRS) part III, Hoehn and Yahr (H&Y) stage, King’s Parkinson’s Disease Pain Scale (KPPS), Brief Pain Inventory (BPI), Non-Motor Symptoms Scale (NMSS), and Beck Depression Inventory (BDI). Spearman’s rank correlation coefficient, multiple regression and multiple index-based clustering algorithms were used for data analysis. Results: The prevalence of pain was 88.6%, was not correlated with age, motor severity (UPDRS part III) or disease duration, whereas a weak correlation with female gender and H&Y stage >2.5 was found. Multiple NMS correlated significantly with pain. Specifically, sleep disturbance had the strongest correlation with pain, followed by depression, gastrointestinal and cardiovascular disturbances. Further analyses showed that sleep and cardiovascular disturbance were independently associated with pain, and that these symptoms clustered together in a subset of PD patients. The relationship between pain, sleep and dysautonomia persisted independently from dopamine replacement therapy. Conclusion: Our study suggests that sleep disruption and cardiovascular disturbance are associated with pain in PD, and possibly identifies a specific subtype within PD patients with pain. Our data also indicate that sleep disruption, pain and dysautonomia may have a common pathophysiology, possibly involving non-dopaminergic pathways.

scholarly journals Intrinsically photosensitive retinal ganglion cell mediated pupil function is impaired in Parkinson’s disease

2017 ◽  
Author(s):  
Daniel S. Joyce ◽  
Beatrix Feigl ◽  
Graham Kerr ◽  
Luisa Roeder ◽  
Andrew J. Zele
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rating Scale ◽  
Early Stage ◽  
Motor Symptoms ◽  
Retinal Ganglion ◽  
Cone Photoreceptor ◽  
Pupil Control ◽  
Pupil Light Reflex ◽  
Non Motor Symptoms

AbstractParkinson’s disease is characterised by non-motor symptoms including sleep and circadian disruption, but the underlying aetiology is not well understood. Melanopsin-expressing intrinsically photosensitive Retinal Ganglion Cells (ipRGC) transmit light signals from the eye to brain areas controlling circadian rhythms and the pupil light reflex. Here we evaluate the hypothesis that these non-motor symptoms in people with Parkinson’s disease may be linked to ipRGC dysfunction. Using chromatic pupillometry, we measured intrinsic (melanopsin-mediated) ipRGC and extrinsic (rod/cone photoreceptor-mediated) inputs to the pupil control pathway in a group of optimally medicated participants with a diagnosis of Parkinson’s disease (PD, n = 17) compared to controls (n = 12). Autonomic tone was evaluated by measuring pupillary unrest in darkness. The PD participants underwent additional clinical assessments using the Unified Parkinson’s disease Rating Scale (UPDRS) and the Hoehn and Yahr scale (H&Y).Compared to controls, the PD group demonstrated an attenuated pupil constriction amplitude in response to long wavelength pulsed stimulation, and reduced post-illumination pupil response (PIPR) amplitude in response to both short wavelength pulsed and sinusoidal stimulation. In the PD group, PIPR amplitude did not correlate with measures of sleep quality, retinal nerve fibre layer thickness, UPDRS or H&Y score, or medication dosage. Both groups exhibited similar pupillary unrest in darkness.We show that melanopsin and the rod/cone-photoreceptor contributions to the pupil control pathway are impaired in people with early-stage Parkinson’s disease. Given that the deficits are independent of clinical assessment severity and are observed despite optimal medication, the melanopsin-mediated PIPR may be a biomarker for the detection of Parkinson’s disease and its continued monitoring in both medicated and unmedicated individuals.

scholarly journals Effect and Potential Mechanism of Electroacupuncture Add-On Treatment in Patients with Parkinson’s Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Fang Wang ◽  
Li Sun ◽  
Xiao-zhe Zhang ◽  
Jun Jia ◽  
Zhuo Liu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Sleep Disturbances ◽  
Rating Scale ◽  
Early Stage ◽  
Life Quality ◽  
Motor Symptoms ◽  
Nonmotor Symptoms ◽  
Nitric Oxide Level ◽  
Disease Rating

Objectives. To explore effectiveness and mechanisms of electroacupuncture (EA) add-on treatment in Parkinson’s disease (PD) patients.Methods. Fifty PD patients were randomly assigned to drug plus EA (D + EA) group and drug alone (D) group. Subjects in D + EA group received stimulation in points of bilateral fengfu, fengchi, hegu, and central dazhui. Participants were evaluated by scales for motor and nonmotor symptoms. Levels of neuroinflammatory factors and neurotransmitters in serum were detected.Results. EA add-on treatment remarkably reduced scores of Unified Parkinson’s Disease Rating Scale (UPDRS) III and its subitems of tremor, rigidity, and bradykinesia and conspicuously decreased UPDRS III scores in patients with bradykinesia-rigidity and mixed types and mild severity. Depression and sleep disturbances were eased, which were reflected by decreased scores of Hamilton Depression Rating Scale, Pittsburgh Sleep Quality Index, and elevated noradrenaline level. Effects of EA add-on treatment on motor symptoms and sleep disturbances were superior to drug alone treatment, markedly improving life quality of PD patients. EA add-on treatment decreased nitric oxide level in serum.Conclusions. EA add-on treatment is effective on most motor symptoms and some nonmotor symptoms and is particularly efficacious in PD patients at early stage. Antineuroinflammation may be a mechanism of EA add-on treatment.

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