REGISTRY Study Protocol Version 2.0 Amendment 1 replacing version 1.0 (version 2.0 includes two new, optional components: ‘donation of biosamples’ and ‘family history questionnaire’) REGISTRY – an observational study of the European Huntington-Disease Network (EHDN) Version 2.0 Date June 2005 Sponsored by High-Q Foundation/HP Therapeutics Foundation, Inc. European Huntington-Disease Network (EHDN) REGISTRY – an observational study of the European Huntington-Disease Network (EHDN) Protocol Version 2.0. Table of content 1. Overview/summary .......................................................................................................3 PROTOCOL TITLE ...............................................................................................................................3 TYPE OF STUDY .................................................................................................................................3 STEERING COMMITTEE.......................................................................................................................3 STUDY CENTRES ................................................................................................................................3 STUDY PERIOD ...................................................................................................................................3 STUDY OBJECTIVES............................................................................................................................3 STUDY POPULATION...........................................................................................................................3 STUDY DESIGN...................................................................................................................................3 NUMBER OF SUBJECTS .......................................................................................................................5 INCLUSION CRITERIA..........................................................................................................................5 EXCLUSION CRITERIA ........................................................................................................................5 ASSESSMENTS AND MEASURES ..........................................................................................................5 SAMPLE SIZE CONSIDERATION ...........................................................................................................6 2. Detailed study description.............................................................................................7 2.1 BACKGROUND AND RATIONAL .....................................................................................................7 2.2. STUDY OBJECTIVES ...................................................................................................................10 2.3. STUDY DESIGN ..........................................................................................................................10 2.3.1. CLINICAL PHENOTYPICAL CHARACTERIZATION......................................................................11 2.3.2. COLLECTION OF BIOLOGICAL SPECIMEN.................................................................................12 2.3.3. COMPLETION OF A FAMILY HISTORY QUESTIONNAIRE (FHQ) ................................................12 2.4. OBSERVATION SCHEDULES .......................................................................................................14 2.6. DESCRIPTION OF THE STUDY POPULATION ................................................................................15 2.6.1. PARTICIPANT SELECTION CRITERIA ........................................................................................15 2.6.2. INCLUSION CRITERIA..............................................................................................................15 2.6.3. EXCLUSION CRITERIA.............................................................................................................16 2.7. DATA SECURITY........................................................................................................................16 2.8. METHOD OF IDENTIFICATION AND RECRUITMENT OF STUDY SUBJECTS ....................................16 2.9. PARTICIPANT INFORMED CONSENT............................................................................................16 2.10. DOCUMENTATION OF CONSENT/ASSENT.................................................................................17 2.11. STUDY PROCEDURES - DESCRIPTIONS......................................................................................18 2.11.1. UNIFIED HUNTINGTON'S DISEASE RATING SCALE 99 (UHDRS 99) .....................................18 2.11.2 FAMILY HISTORY QUESTIONNAIRE (FHQ)............................................................................18 2.11.3. CAG GENOTYPING ..............................................................................................................19 2.11.4. SPECIMEN REPOSITORY: BIOREP IN MILANO (ITALY)..........................................................19 2.12. COSTS TO THE PARTICIPANT ...................................................................................................20 2.13. PARTICIPANT RISK ..................................................................................................................20 2.14. POTENTIAL BENEFIT ...............................................................................................................21 2.15. ALTERNATIVES TO PARTICIPATION .........................................................................................21 2.16. WITHDRAWAL FROM PARTICIPATION......................................................................................21 2.17. END OF STUDY/WITHDRAWALS ...............................................................................................22 2.18. STATISTICAL CONSIDERATIONS ..............................................................................................22 2.19. DATA ANALYSIS .....................................................................................................................23 2.20. MONITORING TRIAL PROGRESS ...............................................................................................23 2.21. FORMS AND DATA HANDLING..................................................................................................23 2.22. MODIFICATION OF THE PROTOCOL ..........................................................................................23 2.23. ADMINISTRATIVE RESPONSIBILITIES .......................................................................................24 REFERENCES....................................................................................................................................25 Appendices .......................................................................................................................27 A INFORMATION AND CONSENT FORMS...........................................................................................27 B. STUDY COORDINATION................................................................................................................46 C. HARDCOPY OF THE CRF..............................................................................................................49 REGISTRY Protocol 2.0 2 1. Overview/summary Protocol Title REGISTRY Type of Study: Prospective observational study with no experimental treatment Steering committee See appendix C Study centres Contributing study sites throughout Europe (currently 100 centres) Study period Prospective, open-ended study. Participants are asked at the time of signing up for REGISTRY (= at the base line visit) to attend as many annual follow up visits as possible Study objectives To collect prospective data on the phenotypical characteristics of Huntington's disease (HD) mutation carriers regardless of whether they display clinical symptoms and signs of HD and of individuals who are part of an HD family (irrespective of their mutation carrier status), in order • to obtain natural history data on a wide spectrum of HD patients, HD mutation carriers and individuals who are part of an HD family • to relate phenotypical characteristics o with genetic factors (‘genetic modifiers’), o with data derived from the study of body fluids (blood, urine – ‘wet biomarker’) and o imaging data (‘dry biomarker’) • to expedite identification and recruitment of participants for clinical trials • to plan for future research studies (observational and interventional trials aimed at better symptom control or aimed at slowing or postponing the onset and progression of HD). To achieve these objectives, participants are asked to donate biosamples (blood and urine) for studies to identify genetic modifiers of HD and to establish and validate biological markers tracking the progressive course of HD; in this context a family history is requested as well in order to understand the relationships of clinical data sets and biosamples from related donors. In addition, non-mutation carrying family members of participants are asked to consider donating biosamples to serve as controls. Study population Participants will either have signs and symptoms of HD, be a member of an HD family or are know to carry the HD mutation. Whilst there are no age restrictions, all participants must either be able to provide consent or have a parent/guardian who can provide parental permission, or have an authorized representative who can provide consent.