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European Huntington’s disease Networkwww.euro‐hd.net
Chair, EHDN and CI Registry: Prof. Bernhard Landwehrmeyer
Sites
Language coordination
Central Coordination
HD community
Lay organisations
Working groups
Executive Committee
Scientific & bioethics advisory board
Sponsor
Registry Steering Committee
EHDN Working Groups
• Advanced stage HD
• Behavioural Phenotype
• Biomarkers
• Biological modifiers and Neuroprevention
• Brainbanking
• Cognitive Phenotype
• Environmental Modifiers
• Functional
• Genetic Modifiers
• Genetic Counseling
• Health Economics
• Imaging
• Juvenile HD
• Motor Phenotype
• Neuroprotective Rx
• Quality of Life
• Standard of Care
• Surgical Therapy
• Symptomatic Rx
• Physiotherapy
RegistryObjectives:
Define phenotypical characteristics of the European HD population
Find out who might be interested and available to participate in studies
Find out how affected people and their relatives are coping
Who can take part:
At risk/gene positive patients with/without symptoms of HD
Companions
Control participants (including gene negative family members)
Registry will facilitate:
Observational studies
Interventional trials
Biomarker detection
Identification of genetic/biological modifiers
Development and validation of clinical outcome measure
Studies of phenotypic subgroups, e.g. JHD
REGISTRYClinical data, annual visits
Optional components:
• Biosamples for identification of genetic modifiers and biomarkers
• Blood sample for CAG repeat testing
• Family History Questionnaire
• Permission to be contacted between visits
Assessment protocolDemographics*Medical history*Medication*Comorbid conditions*CAG repeat length*UHDRS Motor*UHDRS Functional , TFC*BiosamplesCaregiver questionnaireUHDRS PsychiatryUHDRS NeuropsychologyHealth Economics questionnaireSF‐36Family History questionnaire* Core assessment
Quality control/assurance
• Plausibility checks and SOPs
• Rater training and assessment
• Monitoring (online/on‐site)
REGISTRY Site Accrual (Europe)Rank Study Site Subjects Visits Forms1 Leiden 316 769 83242 Manchester 254 481 52573 Cambridge 238 1567 102784 Madrid‐ryc 236 413 41545 London‐nhnn 200 461 34896 Taufkirchen 198 315 35047 Ulm 175 443 50108 Milan 149 313 25949 Copenhagen 137 266 168510 Pozzilli 122 226 200911 Cardiff 119 768 456412 Bochum 108 188 228813 Aberdeen 101 266 211414 Muenster 90 118 208415 Napels 86 188 169816 Rome 84 169 183217 Graz 81 170 192418 Birmingham 76 193 205119 Sheffield 75 135 186420 Madrid‐fjd 75 121 1396
REGISTRY Site Accrual (UK)Study Site Subjects Visits FormsManchester 254 481 5257Cambridge 238 1567 10278London‐NHNN 200 461 3489Cardiff 119 768 4564Aberdeen 101 266 2114Birmingham 76 193 2051Sheffield 75 135 1864London‐Guys 52 110 840Oxford 48 73 547Leicester 47 93 1152Leeds 47 110 866Edinburgh 35 56 749Fife 33 70 872Gloucester 28 58 470Glasgow 17 21 209Plymouth 16 26 222London‐Georges 11 20 241Preston 8 8 124Exeter 8 18 96Total 1413 4534 36005
SouthamptonDorsetPooleMillaton CourtBristolNewcastle
REGISTRY BIOSAMPLES
CAG repeat measurement 1949
Preparation of DNA from Lymphoblastoid cell line 2549
Isolation of lymphocytes 2771
Preparation of plasma 1250
Preparation of urine 2370
EHDN Project - Samples received since November 2005
4 31210
2515
232032
21
4362
5054617774
87105111113
7990
143
110
80
122
165
143139
160
184
141
88
136
205
165
131141
182
211
0
50
100
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200
250no
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Biosamples collection (UK) Study site Total Biosamples First SubmissionsManchester 231 203London‐nhnn 201 153Cambridge 192 184Cardiff 130 116Sheffield 101 67Birmingham 93 70Leeds 68 47Oxford 55 47Fife 51 33London‐guys 51 47Aberdeen 48 48Edinburgh 37 34Leicester 36 33Gloucester 32 27London‐georges 16 10Plymouth 14 13Glasgow 11 11Preston 7 7Exeter 5 5Total 1379 1155
Future aims and objectives for REGISTRY
• Define the European HD cohort– Registry version 3
• Interventional trials– Ethyl‐EPA: completed (EHDN, HSG)– ACR‐16 : dopaminergic stabiliser (EHDN): 26 wk, double‐blind, placebo controlled.
• Epidemiological studies, e.g. Juvenile HD
• Development of assessment tools
Research applications
26 applications received.
Examples of approved projects:
• Improved Function Scale for Pre‐HD
• Exploration of modifier genes for age of onset
– GWA scan
• Late‐stage HD: phenotype and management
• Use of rehabilitation services in HD
Registry 3.0: changes to eCRFsFixed data
Enrolment
DemographicsFixed: Education
Variable: Employment, Updates, Exploratory
Clinical Characteristics (Age of Onset)
Comorbid
Medication
CAG
Registry 3.0
Visit data
• Cognitive brief & extended
• PBA accepted if trained (instead of UHDRS Behaviour)
• Samples‐ plasma collection– 56 sites returned surveys
• 21 Yes (3 UK sites, Aberdeen, Cardiff, London NHNN)
• 11 Maybe
• 24 No
Sub‐study proposals: examples
• Neuropsychiatric– Apathy, Irritability, Depression
• Physiotherapy: outcome measures
• Lifestyle questionnaire: activity/passivity
• Quality of Life
• Cognitive
Optional Components
• Contact between visits (Registry HD, Controls)
• Donation of biosamples (Registry HD, Controls)
• CAG determinations (Registry HD)
• Family History (Registry HD)
• Retrospective data (Registry HD)
• Exploratory* (Registry HD, Controls)
Project (QC)/site specific consent
• Video (Registry HD)
*includes sub‐study proposals
Outlook for 2009
• Protocol finalised by Spring 2009
• Submit to LAC– Translations
– ERB/institutional approval• Country‐specific timelines for approval
• R 3.0 approval to be obtained for all sites before online version released (paper & pencil data collection could begin beforehand)
• Training on webportal, assessments