Ignite Creation Date:
2024-05-06 @ 11:05 AM
Last Modification Date:
2024-10-26 @ 12:39 PM
Study NCT ID:
NCT03421899
Status:
COMPLETED
Last Update Posted:
2023-05-23
First Post:
2017-11-23
Brief Title:
A Study Into the Underlying Biochemical Pathways Involved in Parkinsons Disease Such as Mitochondrial Cellular Powerhouse Dysfunction
Sponsor:
University College London
Organization:
University College London
Study Overview
Official Title:
Systems Medicine of Mitochondrial and Biochemical Parkinsons Disease and Other Related Movement Disorders
Status:
COMPLETED
Status Verified Date:
2023-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
SysMedPD
Brief Summary:
Parkinsons disease PD is a progressive neurological disorder that is increasingly common with age with the incidence rising from approximately 4 people per 10000 in their forties to 2 in 100 over the age of eighty
Our understanding of the causes of PD has rapidly developed in the past two decades but this has not yet translated into any clinically established neuroprotective treatment that slows disease progression There is a growing consensus that the failure of previous efforts is mainly due to the causative diversity of PD ie that PD may have many different causes For example it is known that variants in mitochondrial cellular power house genes can cause specific forms of PD and this may be relevant to other forms of PD
The aim of this study is to attempt to group PD patients based on markers of biochemical dysfunction eg into groups of patients that do and those who do not have evidence of mitochondrial dysfunction to aid in the development of new candidate neuro-protective compounds
The investigators hope by grouping people with Parkinsons into those with and without impaired mitochondrial function the investigators will be better able to develop more targeted treatments aimed at protecting further loss of brain cells that occurs in Parkinsons disease
To achieve this the investigators will study people in two study sites in London with both genetic forms of PD and those with idiopathic PD ie those where there is not a known genetic variant causing PD as well as a healthy control group All groups will undergo standardised clinical assessment to collect information on several aspects of their condition eg disease severity memory problems and sleep problems
Participants will be asked to provide blood urine and optionally cerebrospinal fluid skin samples from which various biochemical assays and genetic analysis will be performed in attempt to group participants based on the results of these tests The study is funded for 3 years with participants being asked to attend for up to 3 study visits each over this time period
Our understanding of the causes of PD has rapidly developed in the past two decades but this has not yet translated into any clinically established neuroprotective treatment that slows disease progression There is a growing consensus that the failure of previous efforts is mainly due to the causative diversity of PD ie that PD may have many different causes For example it is known that variants in mitochondrial cellular power house genes can cause specific forms of PD and this may be relevant to other forms of PD
The aim of this study is to attempt to group PD patients based on markers of biochemical dysfunction eg into groups of patients that do and those who do not have evidence of mitochondrial dysfunction to aid in the development of new candidate neuro-protective compounds
The investigators hope by grouping people with Parkinsons into those with and without impaired mitochondrial function the investigators will be better able to develop more targeted treatments aimed at protecting further loss of brain cells that occurs in Parkinsons disease
To achieve this the investigators will study people in two study sites in London with both genetic forms of PD and those with idiopathic PD ie those where there is not a known genetic variant causing PD as well as a healthy control group All groups will undergo standardised clinical assessment to collect information on several aspects of their condition eg disease severity memory problems and sleep problems
Participants will be asked to provide blood urine and optionally cerebrospinal fluid skin samples from which various biochemical assays and genetic analysis will be performed in attempt to group participants based on the results of these tests The study is funded for 3 years with participants being asked to attend for up to 3 study visits each over this time period
Detailed Description:
Parkinsons disease PD is a progressive neurological disorder that is increasingly prevalent with age with the incidence rising from approximately 4 people per 10000 in their forties to 2 in 100 over the age of eighty Besides motor symptoms such as tremor rigidity bradykinesia and postural instability PD patients often experience a variety of non-motor symptoms such as fatigue depression sleep disturbance and dementia
Although symptomatic treatments exist to partially compensate for motor dysfunction no neuroprotective treatment has yet been established to slow PD progression which inevitably renders patients incapable of living independently Compared to age- and sex-matched controls PD patients are about 5 times more likely to require nursing home care and this care costs about 5 times more than average nursing home care This combined with the European demographic shift toward an increasingly larger fraction of aged individuals creates a social and economic challenge to develop new medications to slow the progression of PD
Our understanding of the aetiopathogenesis of PD has rapidly developed in the past two decades but this has not yet translated into any clinically established neuroprotective treatment that slows disease progression There is a growing consensus that the failure of previous efforts is mainly due to the aetiopathogenic diversity of PD and the estrangement of existing preclinical models from clinical PD For example it is known that mutations in mitochondrial genes can cause monogenic PD and biochemical evidence indicates that in a proportion of cases idiopathic PD is associated with detectable mitochondrial dysfunction
Therefore the investigators focus is on monogenic forms of PD that involve mitochondrial abnormalities as a primary eg Parkin PINK1 or secondary eg LRRK2 GBA1 phenomenon in order to extrapolate to idiopathic PD IPD patients with and without mitochondrial dysfunction Mito-IPD and Amito-IPD respectively Biochemical pathways focusing on but not restricted to mitochondrial function will be assessed using a variety of techniques including biochemical assays on blood urine CSF and tissue samples The investigators will explore both the relevance and measurement of specific biochemical pathways in Parkinsons and related disorders
The main overall objective is to stratify PD patients based on dysfunction in biochemical pathways related to PD This will aid in developing new candidate neuroprotection compounds to slow the progression of neurodegeneration
Although symptomatic treatments exist to partially compensate for motor dysfunction no neuroprotective treatment has yet been established to slow PD progression which inevitably renders patients incapable of living independently Compared to age- and sex-matched controls PD patients are about 5 times more likely to require nursing home care and this care costs about 5 times more than average nursing home care This combined with the European demographic shift toward an increasingly larger fraction of aged individuals creates a social and economic challenge to develop new medications to slow the progression of PD
Our understanding of the aetiopathogenesis of PD has rapidly developed in the past two decades but this has not yet translated into any clinically established neuroprotective treatment that slows disease progression There is a growing consensus that the failure of previous efforts is mainly due to the aetiopathogenic diversity of PD and the estrangement of existing preclinical models from clinical PD For example it is known that mutations in mitochondrial genes can cause monogenic PD and biochemical evidence indicates that in a proportion of cases idiopathic PD is associated with detectable mitochondrial dysfunction
Therefore the investigators focus is on monogenic forms of PD that involve mitochondrial abnormalities as a primary eg Parkin PINK1 or secondary eg LRRK2 GBA1 phenomenon in order to extrapolate to idiopathic PD IPD patients with and without mitochondrial dysfunction Mito-IPD and Amito-IPD respectively Biochemical pathways focusing on but not restricted to mitochondrial function will be assessed using a variety of techniques including biochemical assays on blood urine CSF and tissue samples The investigators will explore both the relevance and measurement of specific biochemical pathways in Parkinsons and related disorders
The main overall objective is to stratify PD patients based on dysfunction in biochemical pathways related to PD This will aid in developing new candidate neuroprotection compounds to slow the progression of neurodegeneration
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None