Active clinical trials for "Parkinson Disease"

The purpose of this study is to examine the long-term effect of Deep Brain Stimulation (DBS) for patients with Parkinson's Disease. We have data for patients operated with DBS since 1998. We wish to examine the effect of stimulation on motor symptoms as well as make a follow-up on complications and side-effects related to treatment. We also wish to follow-up on the quality of life-studies made in the years 2003-2008.

Freezing of gait (FOG) is a disabling episodic gait disturbance that is common among patients with Parkinson's disease (PD). The symptoms of PD generally show an asymmetric onset and progression. In particular, impairments in rhythmicity, symmetry, and bilateral coordination have been reported to be associated with FOG episodes. As the maintenance of gait depends on the precise alternating movements of both legs, irregularities in rhythm, symmetry, and bilateral coordination may impair gait sequence, potentially causing freezing. Results of recent studies strongly suggest that bilateral uncoordinated gait and marked gait asymmetry are associated with FOG. Moreover, it has recently been hypothesized that this may lead to a degree of asymmetric motor function, and that FOG in parkinsonian patients is triggered by a breakdown in the bilateral co-ordination underlying the normal timing of gait. Aim of the study was to evaluate how the modulation of asymmetry through physical therapy might improve gait and FOG.

Voltage fluctuation as a result of brain activity will be recorded into the computer using an EEG device.

Depression is considered to be the most common neuropsychiatric disturbance of PD. In this study, investigators will summarize the treatment profile of PD depression to see if PD depression is properly treated according to guideline.

As seen in previous studies Diffusion Tensor Imaging (DTI) MRI is able to detect very subtle changes in brain tissue even after a very short timescale of hours resulting from performing a cognitive task and learning, We wish to explore and compare those changes to patients with idiopathic PD (IPD) and see if there are changes in the learning process and can we detect them using widely available noninvasive techniques such as MRI.

Over the past decade, experimental data has suggested a complex and bidirectional interaction between the gastrointestinal (GI) tract and the central nervous system (CNS), the so-called "Gut- Brain axis." . Changes in the gut microbiota composition may cause alterations in the gut barrier function and intestinal permeability, affecting not only GI epithelial cells and immune system, but also the ENS including both neurons and glial cells . The bidirectional brain-gut-microbiota axis interactions modulate pro- and anti-inflammatory responses. It has been suggested that the gut microbiota changes associated with intestinal inflammation may contribute to the initiation of α-syn misfolding. There is a growing number of evidence confirming that the gut microbiota alterations precede or occur during the course of PD. Importantly, some genetic risk factors may play a crucial role in the interactions between the brain-gut-microbiota axis with respect to gut inflammation. It has been also shown that the methylation status in the SNCA promoter region may affect α-syn expression and the risk for PD. Therefore, a potential role of the gut microbiota as an epigenetic factor influencing DNA methylation may be speculated. Moreover, genetic variant of the component of innate immune system - TREM2 (Triggering Receptor Expressed on Myeloid cells) has been reported to be associated with a higher risk for PD. The ε4 allele of apolipoprotein E (ApoE) has been shown to increase the risk for dementia in synucleinopathies such as PD. Potentially, ApoE genotype, by influencing bile acid secretion, could affect the composition of the gut microbiota to favor the development of organisms triggering misfolding. Moreover, three single nucleotide polymorphisms in CARD15 gene, known to be associated with Crohn's disease, have been also shown to be over-expressed in PD patients, supporting the observation that GI inflammation contributes to the pathogenesis of PD.

The main goal of this research proposal is to provide, for the first time in humans, a wider understanding of the role of the noradrenergic system both in health and illness (Parkinson's disease) through the use of a newly developed radiotracer (11Carbon [11C]Yohimbine) visualizing alpha-2 (α2) adrenergic receptors (AR) combined with cutting-edge technology, the hybrid positron emission tomography (PET)/magnetic resonance imaging (MRI) scanner. The secondary aim of this study will be to determine whether the expected age- and Parkinson's disease (PD)-related changes in the noradrenergic system are paralleled by changes in neuropsychological performances (such as cognitive, motor and/or olfactory abilities).

The study aims to identify and systematically characterize Parkinson's patients with mutations in the LRRK2 gene. In about 90% of Parkinson's patients the cause of the disease is unclear. Based on current knowledge, it can be assumed that there are several causes and that the causes may be differ between patients; this makes research into the pathogenesis and possible therapies very difficult. In the case of monogenic Parkinson's diseases, which are due to changes in one gene (e.g. LRRK2), the function of the gene and possible disease mechanisms can be investigated. LRRK2-associated Parkinson's syndrome is clinically indistinguishable from idiopathic Parkinson's disease. It is inherited autosomal dominant, that means if one of the two gene copies is altered, the disease occurs. However, the disease does not occur in every mutation carrier, the penetrance is reduced and the mechanisms for that are still unclear. Ideally, knowledge of what influences penetrance could make it possible to exert targeted influence and prevent the disease. The comprehensive investigation of mechanisms of reduced penetrance but also of the effects of the mutation itself requires systematic investigations of as many affected persons as possible. We therefore aim to identify 4,000 people internationally, of them 1,500 with LRRK2-associated Parkinson's syndrome, 500 with LRRK2-mutations but without Parkinson's symptoms, 500 without mutations and without Parkinson's symptoms, 500 Parkinson patients with mutations in other genes than LRRK2 and 1,000 patients with idiopathic Parkinson's disease from the same populations. The participants will undergo a comprehensive survey on Parkinson's symptoms, concomitant diseases, environmental factors and medication and there is the possibility of more detailed genetic examinations. Participants will be asked to donate samples of blood, urine and household dust.

High-frequency deep brain stimulation (DBS) is an effective treatment strategy for a variety of movement disorders including Parkinson's disease, dystonia and tremor1-5, as well as for other neurological and psychiatric disorders e.g. obsessive compulsive disorder, depression, cluster headache, Tourette syndrome, epilepsy and eating disorders6-11. It is currently applied in a continuous fashion, using parameters set by the treating clinician. This approach is non-physiological, as it applies a constant, unchanging therapy to a dysfunctional neuronal system that would normally fluctuate markedly on a moment-by moment basis, depending on external stressors, cognitive load, physical activity and the timing of medication administration. Fluctuations in physical symptoms reflect fluctuations in brain activity. Tracking and responding in real-time to these would allow personalised approaches to DBS through stimulating at appropriate intensities and only when necessary, thereby improving therapeutic efficacy, preserving battery life and potentially limiting side-effects12. Critical to the development of such adaptive/closed-loop DBS technologies is the identification of robust signals on which to base the delivery of variable high-frequency deep brain stimulation. Local field potentials (LFPs), which are recordable through standard DBS electrodes, represent synchronous neuronal discharges within the basal ganglia. Different LFP signatures have been identified in different disorders, as well as in different clinical states within individual disorders. For example, low frequency LFPs in the Alpha/Theta ranges (4-12Hz) are frequently encountered in patients with Dystonia13,14, while both beta (12-30Hz) gamma (60-90Hz) band frequencies may be seen in Parkinson's disease, when the patient is OFF and dyskinetic, respectively15,16. Equally, suppression of these abnormal basal ganglia signals through medication administration or high-frequency DBS correlates with clinical improvement. As such, they represent attractive electrophysiologic biomarkers on which to base adaptive DBS approaches. Until recently, neurophysiological assessments were purely a research tool, as they could only be recorded either intra-operatively or for a short period of time post-operatively using externalised DBS electrodes. However, advances in DBS technology now allow real-time LFP recordings to be simply and seamlessly obtained from fully implanted DBS systems e.g. Medtronic Percept PC. In this study, we will evaluate a cohort of patients with movement disorders and other disorders of basal ganglia circuitry who have implanted DBS systems. Recordings of LFPs and/or non-invasive data such as EEG, limb muscle activation and movement (surface EMG and motion tracking) under various conditions (e.g. voluntary movement, ON/OFF medications, ON/OFF stimulation) will allow us to evaluate their utility as markers of underlying disease phenotype and severity and to assess their potential for use as electrophysiological biomarkers in adaptive DBS approaches. These evaluations in patients with DBS systems with and without LFP-sensing capabilities will take place during a single or multi-day evaluation (depending on patient preference and researcher availability). This study will advance not only the understanding of subcortical physiology in various disorders, but will also provide information about how neurophysiological and behavioural biomarkers can be used to inform personalised, precision closed-loop DBS approaches.

Home-based exercise program focusing on axial rigidity could be used as an adjunct rehabilitation program to improve rotational movement, gait and functional movement associated with axial rigidity in individuals with PD.