Systems Medicine of Mitochondrial and Biochemical Parkinson's Disease and Other Related Movement Disorders
Conditions: Parkinson Disease, Parkinsonism
Sponsor: University College, London

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Project Title:  Systems Medicine of Mitochondrial and biochemical 
Parkinson’s Disease and other related movement disorders 
(SysMedPD) 
 
Protocol 
Version 1.1 
 
04/10/2017 
 
 
Co-Chief Investigators: Prof. Anthony Schapira and Prof Huw Morris 
 
Study Administrator: Dr Philip Campbell 
 
Reference Codes: 
UCL Sponsor Code: 17/0126 
 
Start Date of study: 1/3/17 
Project Duration: 5 years 
 
Abbreviations: Parkinson’s disease – PD; idiopathic Parkinson’s disease – IPD; cerebrospinal 
fluid (CSF); PD patients with detectable mitochondrial dysfunction – mito-PD; PD patients 
without detectable mitochondrial dysfunction – amito-PD; 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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PROTOCOL VERSIONS 
Version Stage 
Versions No 
Version Date 
Protocol updated & 
finalised by; 
Appendix 
No 
detail 
the 
reason(s) for the protocol 
update 
Previous 
1.0 
12/4/17 
AS, HM, PC 
- 
 
Current 
1.1 
04/10/2017 
AS, HM, PC 
Added RNA collection and 
processing 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
DECLARATIONS 
The undersigned confirm that the following protocol has been agreed and accepted and that the 
investigator agrees to conduct the study in compliance with the approved protocol and will adhere to 
the Research Governance Framework 2005 (as amended thereafter), the Trust Data & Information 
policy, Sponsor and other relevant SOPs and applicable Trust policies and legal frameworks. 
I (investigator) agree to ensure that the confidential information contained in this document will not be 
used for any other purposes other than the evaluation or conduct of the clinical investigation without 
the prior written consent of the Sponsor. 
I (investigator) also confirm that an honest accurate and transparent account of the study will be given; 
and that any deviations from the study as planned in this protocol will be explained and reported 
accordingly. 
Chief Investigator:  
Signature:      
 
 
 
Date 21/06/2017 
Print Name (in full): Professor Anthony Henry Vernon Schapira 
Position: Head of Department and Professor of Clinical Neurosciences 
 
On behalf of the Study Sponsor: 
Signature: 
 
 
Date 22/06/2017 
Print Name(in full): Suzanne Emerton 
Position: Sponsorship Officer 
 
 

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1. Trial Personnel 
 
Co-investigators 
Dr Philip Campbell, UCL 
 
 
 
 
p.campbell@ucl.ac.uk  
 
 
2. Summary 
 
Title:  
Systems Medicine of Mitochondrial and biochemical 
Parkinson’s Disease and other related movement disorders 
Short title: 
 
 
SysMedPD 
Objectives: 
Stratification of PD patients based on biochemical markers to   
develop novel neuroprotective therapeutic approaches. 
Type of trial: 
Basic science study with human subjects 
Trial design and methods: 
Genetic analysis, biological material sampling, biochemical 
assays, cell line generation. 
Trial duration per participant: 24 months (up to 3 study visits in 2 years)  
Estimated total trial duration: 5 years (includes 2 years for additional data analysis) 
Planned trial sites: 
Multi-site (Royal Free Hospital Trust and National Hospital for 
Neurology and Neurosurgery, UCLH NHS Trust) 
Total no. participants planned: 160 
Main inclusion/exclusion criteria:  
Inclusion – Affected by Parkinson’s disease (PD) or a related 
disorder or unaffected by PD or related disorder for control 
cohort 
 
Exclusion – Participants with dementia, under 18 years of age. 
Statistical methodology and analysis: 
 
Screening for genetic mutations associated with PD, 
biochemical analysis of biosamples (blood components and 
tissue) by a variety of methods (Seahorse, flow cytometry etc) 
to stratify patients into groups with and without dysfunction in 
the 
studied 
biochemical 
process 
(e.g. 
mitochondrial 
dysfunction). Statistical analysis will include univariate and 
multivariate statistics such as principal component analysis, 
linear mixed models, partial least squares regression and 
ANOVA simultaneous component analysis.  
 
 
 
 
 
 
 

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3. Introduction 
 
3.1 Background: Parkinson's disease (PD) is a progressive neurological disorder that is 
increasingly prevalent with age, with the incidence rising from approximately 4 people per 
10,000 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, our focus is on monogenic forms of PD that involve mitochondrial abnormalities 
as a primary (e.g., Parkin, PINK1), or secondary (e.g., 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 focussing 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. We will explore both the relevance and 
measurement of specific biochemical pathways in Parkinson’s 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. 
3.2 Ethical considerations: The primary ethical considerations here are accurate informed 
consent, data security and potential adverse events related to study procedures, which will 
be monitored through the study. 
3.3 Risks/benefits: This is a basic science study involving procedures to human participants. 
The primary risks of this study will be: 
(1) Potential adverse events related to study procedures which will be mitigated by careful 
monitoring throughout the study 

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(2) Causing increased anxiety about risk to family members of developing PD, which will be 
mitigated (i.) the provision of NHS-based genetic counselling and support where needed and 
(ii.) patient and public engagement through education about the results and implications of 
research as the study progresses. 
4. Objectives 
To identify participants with known monogenic forms of PD and related disorders (PINK1, 
parkin, GBA, LRRK2) for biochemical assessment of blood, urine, CSF and tissue samples to 
identify defects in specific biological pathways (e.g. mitochondrial dysfunction). The most 
informative of these assays will then be applied to participants without genetic mutations 
(IPD) to stratify them based on dysfunction in these biochemical pathways.  
5. Study design 
It is planned that 160 participants will be recruited to the study (comprising 100 with 
idiopathic Parkinson’s disease, 30 with genetic forms of Parkinson’s disease and 30 healthy 
control subjects). This is based upon power calculations conducted by the University of 
Luxembourg (who constructed the initial EU study proposal).  
Participants will be asked to take part in up to 3 visits, one at baseline where a full assessment 
including clinical assessment and biosamples donation will take place, an optional visit for 
skin biopsy and/or CSF sampling and one further visit 1-2 years post entry into the study for 
repeat assessment and biosamples collection for participants with PD only. Data and samples 
will be collected in a standardised format and, following site based subject anonymization, 
will be entered onto a secure web-based database. To develop a patient registry, subjects can 
provide consent for permission to be contacted if further/additional research projects were 
to become available.  
All participants must consent to the core protocol of clinical assessment and blood and urine 
donation. CSF and skin biopsy consent is highly desirable but optional. Skin biopsies will be 
requested from some study participants including unselected PD patients, healthy controls 
and PD patients with defined genetic and/or biochemical phenotypes. If participants are 
identified as being in particular cohorts of interest post baseline assessment/sampling 
analysis (e.g. the mito-PD or amito-PD groups) then cell lines generated from skin biopsies 
from these participants will be used to create advanced cell models, such as induced 
pluripotent stem cells and dopamingeric neurons for further biochemical analysis and 
validation of initial findings. All monogenic PD participant skin biopsy samples will be used to 
generate such models.  
Patients will be asked if they want to be informed of the availability of NHS genetic or 
biochemical tests which emerge as a result of this research.  Participants will not be made 
aware of the cohort they fall into as currently this will not change their medical care, however 
consent will be sort to re-contact patients based on the results of this study if these results 
suggest they will be eligible for novel therapies for PD or would be eligible to take part in 
future studies or clinical trials related to Parkinson’s disease. Control subjects will be asked to 

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complete baseline clinical assessments and donate biosamples but will not be asked to return 
for any further study visits.  
 
 
Table 1 – SysMedPD overview 
 
5.1 Inclusion/exclusion criteria:  
Inclusion 
1. Diagnosed with PD, or a related condition (e.g. Parkinson’s plus, dystonia, 
tremor) or healthy control participant 
 
 
2. Age 18 years or over  
Exclusion 
1. Lack of capacity to consent to participate in the project 
 
Visit 1 
Visit 
2 
(optional) 
Visit 3 - 24-48 months (for those 
affected by PD only) 
Study personnel administered 
 
 
 
Informed consent 
X 
 
X 
Demographic information 
X 
 
X 
Parkinson’s disease history 
X 
 
X 
Past medical history 
X 
 
X 
Medication history 
X 
 
X 
Family history 
X 
 
X 
Environmental exposure 
X 
 
X 
MDS-UPDRS clinician 
X 
 
X 
Tremor Spirals 
X 
 
X 
Handwriting 
X 
 
X 
MoCA 
X 
 
X 
Patient completed 
 
 
 
MDS-UPDRS patient 
X 
 
X 
PDSS2 
X 
 
X 
ESS 
X 
 
X 
HADS 
X 
 
X 
WHO QoL (BREF) 
X 
 
X 
Biomarkers 
 
 
 
Blood for DNA 
X 
 
X 
Blood for RNA 
X 
 
X 
Blood PBL/LCL 
X 
 
X 
Blood for Serum 
X 
 
X 
Blood for Plasma 
X 
 
X 
Blood for cellular components 
X 
 
X 
Urine 
X 
 
X 
Optional Assessments 
 
 
 
Video assessment 
X 
 
X 
CSF 
 
X 
 
Skin biopsy  
 
X 
 

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Additional lumbar puncture and skin biopsy exclusion criteria 
1. Anticoagulants such as warfarin 
2. Known coagulation abnormalities – known coagulopathy 
3. Lumbar spinal surgery within 6 months prior to assessment, or any lumbar 
spinal surgery that interferes with anatomy of the inter-vertebral space 
(LP).  
4. History of chronic or repeat CSF leakage following previous lumbar 
puncture or history of spontaneous or traumatic intracranial hypotension 
(LP) 
5. Active infectious process 
6. Allergy/hypersensitivity to local anaesthetic 
5.2 Recruitment: Participants will be identified in the following ways: 
a) By the study team from existing biobank studies that UCL is collaborating on, where 
the patient has consented to be re-contacted.  
b) By the clinical care team/ their treating physicians through movement disorder and 
neurology clinics in the course of normal clinical care.  
c) Participants may contact the study team directly, for example after reading adverts 
on PD charity websites, in this instance participants will need to complete and return a 
‘permission to contact form’ to the study team.  
d) Participants friends/spouses who plan to attend study/clinic visits with the 
participant may also be approached to join the study as control subjects. This will be done by 
the study team. During study visits participants can be given permission to contact forms and 
information leaflets to give to friends/spouses who they feel may want to enrol in the study 
as a control subject 
Participants will be provided with written information on the study before they 
participate, either via email or regular post. The primary research clinics will be based at the 
Royal Free London Foundation Trust and UCLH. Participants will be approached by their 
caregiver in the course of normal clinical care or by caregivers holding registries of patients 
who have agreed to be contacted for research purposes.   
5.3 Consent: Written Informed consent will be obtained by individuals trained in GCP; and in 
consent procedures specific to this study. The consent process will be guided by a standard 
operating procedure (SOP). Standardised patient information sheets (PIS) and consent forms 
will be used. Participants can withdraw from the study any time without giving reasons.  
5.4 Study assessments: Potential participants will sign an informed consent form prior to any 
study-related procedures, which will involve agreement to: 
1. A brief structured clinical interview (30 mins) that will obtain details of patient 
demographics, PD history, past medical history, medication history, family history and 
environmental exposures (based on MERQ-PD questionnaire). This will also include 
reviewing participants NHS records.  

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2. A structured clinical examination (15mins) consisting of the following standardised 
examinations: 
 
a. MDS-UPDRS 
 
b. Montreal Cognitive Assessment (MoCA) 
 
c. Handwriting and spiral drawing assessment 
Examinations may be videotaped for confidential research analysis, for example 
validation of clinical diagnosis, and rating scale assessment by another member of the 
research team 
3. Standardised validated patient self-completion questionnaires (20mins – can be 
done at home) including Epworth sleepiness scale (ESS), Parkinson’s disease sleep 
scale 2 (PDSS2), WHO Quality of Life scale short version (WHOQol – BREF), Hospital 
Anxiety and Depression scale (HADS) and Scales for Outcomes in Parkinson's disease - 
Autonomic (SCOPA-AUT). 
5.5 Biosamples: All participants will be invited to donate blood, urine and CSF at the initial 
study visit. All samples will be taken and stored using a standardised protocols. Participants 
will be asked to fast for 10-12 hours where possible before biosamples are taken. All samples 
will be labelled with a unique study identifier.  
 
a. Blood – each participant will be invited to donated up to 100mls of blood for DNA, 
analysis, RNA analysis, storage of immortalised peripheral blood lymphocytes (PBLs) (see 
below), plasma and serum samples, and extraction of blood cells (red blood cells, white blood 
cells and platelets) for biochemical assessment (such as mitochondrial function).  
 
b. Urine - a mid-stream urine sample will be collected from each participant 
 
c. CSF – Consent to CSF sampling is highly desirable but optional. For participants who 
agree to donate CSF a lumbar puncture will be performed. An information sheet on lumbar 
puncture will be provided to the participant. Local protocols should include the ability to 
perform a blood patch if necessary for persisting low- pressure headache. Lumbar punctures 
for CSF collection are performed using a small calibre needle in either a sitting or lateral 
decubitus position. CSF is obtained via gravity flow into polypropylene tubes. The first 0.5-1ml 
will be discarded due to potential contamination with blood. 5-10ml of CSF will then be 
collected for storage. Participants who are having a lumbar puncture as part of their routine 
clinical care, treatment or as a research procedure will be asked if they will donate surplus 
CSF for research purposes. 
 
d. Skin biopsy – Skin biopsy consent is highly desirable but optional. A proportion of 
participants will be asked to donate a skin biopsy. Skin biopsies will yield both skin and 
underlying fat samples. The area for biopsy will be scrubbed with 70% isopropyl alcohol and 
local anaesthetic will be instilled prior to removal of a skin and underlying fat sample by sterile 
punch biopsy instrument (4- 6mm depending on the participant’s build). The skin will be 
closed with steristrips in most cases. Occasionally it is anticipated that a single stitch will be 
required and if this is the case the participant will be instructed to attend their GP surgery to 

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have the stitch removed by the practice nurse in one week’s time. The patient will be given 
an information sheet on post skin biopsy management. Skin punch will be carried out by 
clinically qualified personnel at all centres or where appropriate, at the participant’s home.  
The skin and fat sample will be transferred to the laboratory for further processing. Here 
fibroblast (from skin) and adipose stem cell (from fat) lines will be established using standard 
methods. 
5.6 Controls: Individuals who are not blood relatives of the patient are eligible to participate 
as an unaffected control. Typically this will be the spouse or a close friend of the affected 
SysMedPD patient, but not their son, daughter or sibling. Permission to contact forms and 
patient information leaflets will be given to participants in the study to pass onto 
friends/spouses who would be eligible to enrol as control subjects. Alternatively, at 
study/clinic visits where a participant is accompanied by a friend/spouse who would be 
eligible to enrol as an unaffected control, the study team will invite the individual to take 
copies of the participant information sheet and consent form, as well as a ‘permission to 
contact form’. If they would like to enrol then they can return the permission to contact form 
to the study team. Finally unaffected controls can contact the study team directly, for 
example after reading adverts on PD charity websites. In this instance they would need to 
complete and return a ‘permission to contact form’ to the study team. Unaffected individuals 
can participate by completing study questionnaires/assessment and donating blood samples, 
and if possible CSF collection and skin biopsy. They will not be required to undergo a second 
follow up visit.  
 
6. Sample analysis/processing 
 
6.1 Screening for genes related to PD: Blood samples will be sent to UCL Institute of 
Neurology Neurogenetics Lab for DNA extraction and storage to be carried out in accordance 
with the analytical plan agreed with the Chief Investigator. The Neurogenetics Laboratory will 
process, store and dispose of blood samples in accordance with all applicable legal and 
regulatory requirements, including the Human Tissue Act 2004 and any thereto. Genetic 
analysis may include large scale sequence, copy number and single nucleotide variant 
analysis.  Similarly RNA will be extracted from whole blood and analysed using RNA 
sequencing (RNAseq). 
 
6.2 ECACC: Consent will also be sought for a coded blood to be sent to the European Collection 
of Cell Cultures - Porton Down (ECACC) for storage of peripheral blood lymphocytes (PBLs) 
and ultimately the preparation of immortalised cell lines for affected individuals only. No 
personal identifiers will be sent with this sample. However to enable the cell line to be of 
optimal use to the research community, strictly limited details of the subject will accompany 
the sample, specifically sex, race and year of birth. No further personal identifying details will 
be released to ECACC. The code linking the samples will be kept strictly confidential by the 
research group, on the encrypted NHS computer system in a folder whose access restricted 
by the study PI. Subjects can request withdrawal of their samples from ECACC at any point. 
The European Collection of Cell Cultures will process, store and dispose of blood samples in 
accordance with all applicable legal and regulatory requirements, including the Human Tissue 
Act 2004 and any amendments thereto. The custodian and Human Tissue Act Designated 

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Individual for ECACC is Julie E. Russell (MSc C.Biol MSB) - Head of Culture Collections                           
for Public Health England (PHE) (contact details: email: julie.e.russell@phe.gov.uk; direct 
telephone: +44 (0) 1980 612661) 
 
6.3 Assessment of biochemical pathways: This will involve analysis of plasma, serum, urine, 
CSF, blood cellular components and tissue taken from participants. If participants have 
already donated samples to another approved study lead by the principle investigators or 
their collaborators (such as the Clinical Neurological Disorders DNA and Serum Research Bank 
- CANDAS), and there is consent to use samples in collaborating projects, then these samples 
will be requested from the CANDAS study to reduce patient burden.  Various pathways 
thought to be involved in PD (such as mitochondrial dysfunction) will be investigated using a 
range of laboratory techniques such as flow cytometry, seahorse extracellular flux analysis 
and metabolomic analysis. The aim is to use these pathways to stratify participants into 
cohorts with and without dysfunction in the studied biochemical pathway.  
 
6.4 Collaboration – incoming data/samples: The research group may analyse anonymous 
samples provided by collaborators where an MTA is in place and where samples have been 
collected with appropriate local ethical approval.  
 
6.5 Collaboration – outgoing samples: The research group will collaborate with national and 
international groups engaged in neurology research, principally in the EU for analysis as 
above. This project is part of a large European wide project involving multiple sites across 
Europe and is being funded primarily by an EU ‘Horizon 2020’ grant. This will involve sharing 
anonymised samples for specific analysis which will be carried out at other sites, e.g. 
“metabolomics” in the Netherlands.  Pseudo-anonymised data will accompany the samples. 
Appropriate material transfer agreements (MTAs) will be used. Participants will be asked 
whether they consent to sharing of their pseudo-anonymized data. 
 
7. Feedback to participants and the Wider Community 
 
7.1 Individual based: Participants will be asked at the time of entry to the study whether they 
would wish to be informed if the project discovers they have a genetic mutation related to 
PD that has a validated NHS genetic test. If they elect to be informed, they will be contacted 
by letter. This will allow the individual to seek formal NHS (or equivalent) neurogenetics 
disease gene confirmation via an accredited genetics service and for potentially at risk family 
members to seek predictive counselling and testing via an NHS clinical genetics service if they 
wish. It will be emphasized that research results cannot be used for diagnosis or genetic 
counselling but that the appropriate NHS services will be used and that we will link closely 
with normal NHS care. The main genetics services with which we will work will be the 
Neurogenetics clinic, National Hospital for Neurology and Neurosurgery and Royal Free 
Hospitals. Where an individual does not want feedback, no communication of specific 
research findings will be made.  
 
Participants will also be asked at time of entry into the study whether they would consent to 
be re-contacted based on results (genetic or biochemical) generated from this study should 
these results indicate they would be eligible for new research studies or therapies for 

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Parkinson’s disease.  The contact will involve providing information about new studies with 
no commitment to enter these studies.  
 
7.2 Incidental identification of health problems: There is the potential to detect 
unexpected, unrelated pathology in individuals undergoing clinical evaluation and clinical 
test. In such a case, the clinical research team will discuss the situation with the study 
participant and advise they see their GP to discuss whether specialist referral to assess and 
potentially treat these symptoms is appropriate. Relevant results with also be fed back to 
the participant’s GP with their consent. This possibility will also be made clear in the consent 
form signed by the study participant.  
 
7.3 Scientific publication of results: will be via written reports to scientific journals. These 
publications will involve publication of anonymized information in scientific journals and the 
results of the research listed above.  
 
8. Adverse events 
 
All adverse events will be recorded in the case records. Adverse events may include side 
effects from the assessments performed but may also include signs or symptoms that may or 
may not be related to the study procedures. Appropriate local procedures will be in place for 
reporting of adverse events.  
 
8.1 Reporting Serious Unexpected Adverse Events: All Serious Unexpected Adverse Events 
to a research subject in the study must be reported immediately to the sponsor using the 
following email address research-incidents@ucl.ac.uk.  
A Serious Adverse Event  
 Results in death  
 Is life Threatening  
 Requires Hospitalisation or prolongation of hospitalisation  
 Results in persistent or significant disability or incapacity  
 Consists of a congenital anomaly or birth defect  
 Any other serious medical occurrence  
 
Serious Adverse Events will be documented from the point of enrolment until the patient is 
exited from study. Information recorded and reported shall include  
 A description of the event  
 The date of event onset  
 The relatedness of the event to the procedure  
 The expectedness of the event  
 The outcome of the event  
 The date the event was first noticed by, or reported to the investigator  
 
All ongoing Serious Adverse Events will be followed-up until the last study visit.  
 
8.2 Reporting Incidents: All incidents must be reported through the appropriate Trust 
incidents reporting system. Where no Trust is involved the incident should be reported by 
completing form at http://www.ucl.ac.uk/jro/postapproval  

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Where the study is being conducted at UCLH then the incidents should be reported through 
Datix.  
 
An incident in a research study is  
 Something that should not have happened OR  
 Something that should have happened but didn't  
 
Which significantly effects any of the following 
 The rights and well-being of the research subject  
 The scientific value of the study 
 The compliance of the study with all relevant legal rules or ethics guidance including 
the Data Protection Act and the Human Tissue Act.  
 The reputation of UCL  
 
This includes a requirement to report all serious breaches of protocol or GCP (if applicable). 
 
9. Data and sample management 
 
9.1 Storage of data: Patient identifiable source data will be stored in clinical subject folders 
in locked cabinet/locked room at study centres. Electronic scanned copies of primary consent 
forms and primary NHS records (e.g. NHS copy clinic letters, discharge summaries, previous 
genetic tests and scans) will be stored on the main NHS data store or on the secure database. 
Personally identifiable data will be transferred by mail, fax or 256-AES encrypted digital 
communication.  
 
Participants will have a unique study ID generated using a standard labelling procedure. A 
‘code-break’ will exist on the secure network if the need to identify a patent is required. Only 
the study primary investigators (Prof Anthony Schapira and Prof Huw Morris) and the study 
co-ordinator (Dr Philip Campbell) will have access to this ‘code-break’. 
 
The main study database will be held in pseudo-anonymised form (study number) on a web 
application called REDCap, which is PHP software with a MySQL database back-end, created 
by Vanderbilt University for creating and managing online databases and surveys. It is tried 
and tested and popular among research institutions particularly for use in managing clinical 
studies and trials, longitudinal studies and surveys. REDCap has password protected and 
granular access to data and software modules, as well as logging and audit trails of any 
activity. It enforces a robust security model, with password requirements/expiry and time-
outs, and any communication is encrypted through SSL. The database will be on a Linux server 
virtual machine hosted on a secure cloud hosting service. The web host, network connection 
and storage is Information Governance Toolkit compliant and ISO27001 certified following 
data security best practice. The database server will be backed up to two separate locations 
with server redundancy, meaning if one server goes down then a mirror will be up instead. 
No patient identifiable data will be held on this web based system.  
 
Personally identifiable information will be held on a database which is separated from the 
main study database, with access restricted to the study coordinator and chief investigator. 

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The Study Coordinator will be responsible for enforcing a secure and robust system for 
maintaining coherent de-identified participant IDs at the central database. 
 
Study clinical and genetic data will also be stored in pseudo-anonymised form with study code 
number on University (UCL) computer systems or other secure database. 
 
Anonymised data with study code and year of birth may be shared with external collaborators 
as indicated above. Participants' personal data, including their name, postcode, date of birth 
and NHS number will be shared with the NHS Health and Social Care Information Centre in 
order to provide information about their health status. Storage and handling of data will 
follow Standard Operating Procedures. The databases will be maintained until 2037 for 
genetic/epidemiological research, under the custodianship of Prof. Anthony Schapira or Prof. 
Huw Morris to enable the long term follow up of participants recruited in this study. It may 
become important for participants to be re-contacted if new treatments or NHS tests become 
available as a result of this research.  
 
9.2 Archiving: UCL recognises that there is an obligation to archive study-related documents 
at the end of the study (as such end is defined within this protocol).  The Chief Investigator 
confirms that he will archive the study master file at Royal Free for the period stipulated in 
the protocol and in line with all relevant legal and statutory requirements. The Principal 
Investigator agrees to archive the site’s study documents for 10 years following the study end, 
and in line with all relevant legal and statutory requirements.  
 
At the end of the research all existing biosamples from the study will be transferred to the 
Clinical Neurological Disorders DNA and Serum Research Bank (CANDAS) at UCL, under the 
custodianship of Prof Huw Morris (co-principle investigator of this study).  
 
9.3 Sample handling: Plasma, serum, urine, CSF and peripheral blood lymphocytes (PBLs) will 
be stored in secure freezers at the Royal Free Hospital Clinical Neuroscience Laboratories; 
Royal Free Hospital Biobank or National Hospital for Neurology Neurogenetics Laboratory. 
 
9.4 Blood/DNA/RNA: will be extracted and then stored in a local or collaborating DNA/RNA 
lab (e.g. Institute of Neurology Neurogenetics lab, Department of Clinical Neuroscience 
Laboratory Royal Free Hospital) and/or processed at the European Consortium for Cell 
Cultures (ECACC), Salisbury, Wiltshire.  
 
9.5 Cell lines: will be stored at Royal Free Hospital Clinical Neuroscience Laboratories; Royal 
Free Hospital. Cell lines may be submitted for bio-banking at ECACC (see section 6.2), 
StemBANCC, and collaborating laboratories in the UK and worldwide. 
 
StemBANCC is a large-scale international multi-site partnership in the area of stem cell 
research. It brings a consortium of 35 partners together who share their experience in the 
field. It is a resource for developing new disease models and testing new therapies, funded 
by several partners including the UK Medical Research Council.  It is a consortium which 
includes UCL and is overseen by a Scientific Ethical and Advisory Board and managed by Dr 
Zameel Cader, University of Oxford. 
 

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9.6 Quality assurance: An ongoing record of completion of study procedures will be kept. 
Protocol changes and personnel changes will be notified to REC, Local Trusts and other 
appropriate organizations.  
 
9.7 Insurance: University College London holds insurance against claims from participants for 
harm caused by their participation in this clinical study. Participants may be able to claim 
compensation if they can prove that UCL has been negligent. However, if this clinical study is 
being carried out in a hospital, the hospital continues to have a duty of care to the participant 
of the clinical study. University College London does not accept liability for any breach in the 
hospital’s duty of care, or any negligence on the part of hospital employees. This applies 
whether the hospital is an NHS Trust or otherwise 
 
10. Training 
 
The Chief Investigators will review and provide assurances of the training and experience of 
all staff working on this study.  Appropriate training records will be maintained in the study 
files. Written Informed consent will be obtained by individuals trained in GCP. MDS-UPDRS 
assessment will only be carried out by those trained to do.  
 
11. Intellectual property 
 
Intellectual property agreements have been agreed regarding this project, see section 8 
(page 18) of signed final version of consortium agreement for the project ‘SysMedPD’. 
 
12. Supply of equipment 
 
UCL owned research equipment (e.g Department of Clinical Neuroscience video recorder) 
will be used. 
 
13. Statement of Compliance  
 
The Chief Investigators will ensure that this study is conducted in accordance with the 
principles of the Declaration of Helsinki and in full conformity with relevant regulations and 
with the ICH Guidelines for Good Clinical Practice (CPMP/ICH/135/95) July 1996