Brain iron chelation by deferiprone in a phase 2 randomised double-blinded placebo controlled clinical trial in Parkinson’s disease

Abstract Background Dopamine transporter single-photon emission computed tomography (DaT-SPECT) can quantify the functional integrity of the dopaminergic nerve terminals and has been suggested as an imaging modality to verify the clinical diagnosis of Parkinson’s disease (PD). Depending on the stage of progression, approximately 5–15% of participants clinically diagnosed with idiopathic PD have been observed in previous studies to have normal DaT-SPECT patterns. However, the utility of DaT-SPECT in enhancing early PD participant selection in a global, multicenter clinical trial of a potentially disease-modifying therapy is not well understood. Methods The SPARK clinical trial was a phase 2 trial of cinpanemab, a monoclonal antibody against alpha-synuclein, in participants with early PD. DaT-SPECT was performed at screening to select participants with DaT-SPECT patterns consistent with degenerative parkinsonism. Acquisition was harmonised across 82 sites. Images were reconstructed and qualitatively read at a central laboratory by blinded neuroradiologists for inclusion prior to automated quantitative analysis. Results In total, 482 unique participants were screened between January 2018 and May 2019; 3.8% (15/398) of imaged participants were excluded owing to negative DaT-SPECT findings (i.e., scans without evidence of dopaminergic deficit [SWEDD]). Conclusion A smaller proportion of SPARK participants were excluded owing to SWEDD status upon DaT-SPECT screening than has been reported in prior studies. Further research is needed to understand the reasons for the low SWEDD rate in this study and whether these results are generalisable to future studies. If supported, the radiation risks, imaging costs, and operational burden of DaT-SPECT for enrichment may be mitigated by clinical assessment and other study design aspects. Trial registration ClinicalTrials.gov identifier: NCT03318523. Date submitted: October 19, 2017. First Posted: October 24, 2017.

Download Full-text

A controlled clinical trial investigating the effects of cycle ergometry training on exercise tolerance, balance and quality of life in patients with Parkinson’s disease

Disability and Rehabilitation ◽

10.3109/09638288.2012.694962 ◽

2012 ◽

Vol 35 (5) ◽

pp. 382-387 ◽

Cited By ~ 17

Author(s):

Paula Lauhoff ◽

Niamh Murphy ◽

Colin Doherty ◽

N. Frances Horgan

Keyword(s):

Quality Of Life ◽

Parkinson’S Disease ◽

Clinical Trial ◽

Parkinson's Disease ◽

Exercise Tolerance ◽

Cycle Ergometry ◽

Controlled Clinical Trial

Download Full-text

Physical therapy and Parkinson's disease: A controlled clinical trial

Neurology ◽

10.1212/wnl.44.3_part_1.376 ◽

1994 ◽

Vol 44 (3, Part 1) ◽

pp. 376-376 ◽

Cited By ~ 144

Author(s):

C. L. Comelia ◽

G. T. Stebbins ◽

N. Brown-Toms ◽

C. G. Goetz

Keyword(s):

Parkinson’S Disease ◽

Clinical Trial ◽

Parkinson's Disease ◽

Physical Therapy ◽

Controlled Clinical Trial

Download Full-text

The effect of eating utensil weight on functional arm movement in people with Parkinson’s disease: a controlled clinical trial

Clinical Rehabilitation ◽

10.1177/0269215509342334 ◽

2009 ◽

Vol 23 (12) ◽

pp. 1086-1092 ◽

Cited By ~ 11

Author(s):

Hui-Ing Ma ◽

Wen-Juh Hwang ◽

Pei-Luen Tsai ◽

Yung-Wen Hsu

Keyword(s):

Parkinson’S Disease ◽

Clinical Trial ◽

Parkinson's Disease ◽

Arm Movement ◽

Controlled Clinical Trial

Download Full-text

Adapted functional training versus Mat Pilates in motor and non-motor symptoms of individuals with Parkinson's disease: study protocol for a randomized controlled clinical trial Functional training versus Mat Pilates in Parkinson's disease

10.21203/rs.3.rs-62891/v1 ◽

2021 ◽

Author(s):

Jéssica Moratelli ◽

Kettlyn Hames Alexandre ◽

Leonessa Boing ◽

Melissa de Carvalho Souza Vieira ◽

Adriana Coutinho de Azevedo Guimarães

Keyword(s):

Parkinson’S Disease ◽

Clinical Trial ◽

Parkinson's Disease ◽

Cardiorespiratory Fitness ◽

Control Group ◽

Controlled Clinical Trial ◽

Motor Symptoms ◽

Functional Training ◽

Randomized Controlled ◽

Non Motor Symptoms

Abstract Background: Motor and non-motor symptoms affect the life of those living with Parkinson's disease, and it is clear that exercise offers benefits in these aspects. However, the effects of adapted functional training interventions and the Mat Pilates as a form of rehabilitation for the disease in question have not yet been established. Thus, this study aims to propose an adapted functional training protocol and Mat Pilates for individuals with Parkinson's disease and to evaluate the effects on motor symptoms (balance, cardiorespiratory fitness, lower and upper limb strength, flexibility and agility), as well as , in non-motor symptoms (cognition, depressive symptoms, mood state, anxiety and finitude) by means of a randomized controlled trial. Methods: Protocol for a randomized clinical trial in which 45 individuals with Parkinson's disease will be recruited and randomly allocated to one of three groups: (1) functional training; (2) Mat Pilates; (3) control group. Both intervention groups will have 60-minute classes twice a week for 12 weeks. The primary outcome will be analyzed by balancing with the Mini-BESTest test. Secondary outcomes will include cognition, aging perspective, mood, anxiety, depression, mobility, muscle strength, handgrip strength, flexibility, range of motion, and cardiorespiratory fitness. The evaluations will be performed in the pre-intervention period (baseline), after 12 weeks of intervention, after 3 months, 6 months and 1 year of intervention. Discussion: This will be the first randomized trial to compare the effects of functional training and Mat Pilates in a population with Parkinson's disease. It is hypothesized that improvements in motor and non-motor symptoms will be greater and more lasting after functional training and Mat Pilates interventions than those that maintain their routine activities, given the benefits of exercise and the unprecedented protocols in this disease.Trial registrationRegistry name: Registro Brasileiro de Ensaios Clínicos (ReBEC)Registration number: RBR-6ckggnDate of registration: September 29, 2020. Trial was prospectively registered

Download Full-text

Combined Metabolic Activators Improve Cognitive Functions without Altering Motor Scores in Parkinson's Disease

10.1101/2021.07.28.21261293 ◽

2021 ◽

Author(s):

BURAK YULUG ◽

OZLEM ALTAY ◽

XIANGYU LI ◽

LUTFU HANOGLU ◽

SEYDA CANKAYA ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Placebo Group ◽

Cognitive Functions ◽

Plasma Proteins ◽

Metabolic Abnormalities ◽

Phase 2 ◽

Nicotinamide Riboside ◽

Phase 2 Study ◽

Double Blinded

The neuropathologic hallmarks of Parkinson's disease (PD) are associated with mitochondrial dysfunction and metabolic abnormalities. We have reported that the Combined Metabolic Activators (CMA), consisting of L-serine, nicotinamide riboside, N-acetyl-L-cysteine, and L-carnitine tartrate can be used in treating metabolic abnormalities. These metabolic activators are the precursors of nicotinamide adenine dinucleotide (NAD+) and glutathione (GSH) and used in activation of mitochondrial and global metabolism. We have performed a placebo-controlled, phase-2 study in Alzheimer's disease (AD) patients and reported that the cognitive functions in AD patients is significantly improved 29% in the CMA group whereas it is improved only 14% in the placebo group after 84 days of CMA administration. Here, we designed a randomized, double-blinded, placebo-controlled, phase-2 study in PD patients with CMA administration. We found that the cognitive functions in PD patients is significantly improved 21% in the CMA group, whereas it is improved only 11% in the placebo group after 84 days of CMA administration. We also found that the administration of CMA did not affect motor functions in PD patients. We performed a comprehensive multi-omics analysis of plasma proteins and metabolites, and revealed the molecular mechanism associated with the treatment of the patients. In conclusion, our results show that treating PD patients with CMAs leads to enhanced cognitive function, as recently reported in AD patients.

Download Full-text