Spanish Society of Neurology.

Rare Disease Registries

Javier Arpa

Madrid, March, 4th - 5th, 2013

Study Groups of SEN

Grupos de Trabajocoordinador-delegadoDr. Jerónimo Sancho Rieger.

Grupo de Estudio de Humanidades e Historia de la Neurología

Grupo de Estudio de Epilepsia

Grupo de Estudio de la Neurología del Trabajo

Grupo de Estudio de Cefaleas

Grupo de Estudio de Enfermedades Desmielinizantes

Grupo de Estudio de Enfermedades Neuromusculares

Grupo de Estudio de los Trastornos del Movimiento

Grupo de Estudio de Enfermedades Cerebrovasculares

Grupo de Estudio de Neuroepidemiología

Grupo de Estudio de Conducta y Demencias

Grupo de Estudio de Neurogeriatría

Grupo de Estudio de Trastornos de la Vigilia y el Sueño

Grupo de Estudio de Neurogenética

Grupo de Estudio de Gestión y Asistencia Neurológica

Grupo de Estudio sobre Dolor Neuropático

Grupo de Estudio de Neuroquímica y Neurofarmacología

Grupo de Estudio de Neuroncología

Grupo de Estudio de Neuroimagen

Grupo de Estudio de Neuro-oftalmología

Grupo de Estudio de Neurología Crítica e Intensivista

Comisión de Estudio de Ataxias y Paraparesias Espásticas Degenerativas (CEAPED)

Committee of Rare Diseases of SEN

Coordinator: Dr. Mª Carmen Calles Hernández

Members: Dr. Javier Arpa Gutiérrez Dr. Samuel Ignacio Pascual Pascual Dr. Pedro José García Ruiz-Espiga

ISSUES: 1.- Improve recognition of RD by Neurologists 2.- Impel creating Reference Centers in RD 3.- Improve information channels for Neurologists 4.- Improve the level of participation of SEN in other

National or International Research Organizations in RD like CIBERER

5.- Strengthen the Spanish RD registries of the Institute Carlos III

6.- Boost database of genetic mutation in RD

Joint Societies of SEN

Sociedades adheridas

 

Club Español de Neuropatología

Club EMG

Sociedad Española de Enfermería Neurológica SEDENE

SONES

Sociedad Española de Neuro-rehabilitación

CEAPED

Study Commission of Degenerative Ataxia and Spastic Paraparesis

2011

Coordinator: Dr. F.Javier Arpa Gutiérrez

Secretary: Mª José Abenza Abildúa

Members:

Dr. Samuel I. Pascual Pascual

Dr. Francisco Javier Rodríguez de

Rivera Garrido

Board of Directors

CEAPED Minutes(23/NOV/2012)

The elaboration of a Map of the Spanish Health Care with regard to Degenerative Ataxia and Spastic Paraparesis was agreed. A survey will carried out directed to all the members of SEN.

Participate in clinical trial at home and abroad. It is agreed to carry out a training course in Degenerative Ataxia

and Spastic Paraparesis during 2013 (Villagarcía de Campos, on June 2013).

Collaboration with other Study Groups of SEN (Genetics, Neuromuscular, Movement Disorders, General Neurology...), NEUROGENES Association, and other Medicine Specialities.

It is considered fundamental to maintain a close collaboration with CIBERER and CIBERNED. Translational Research.

Collaboration with European Groups of Hereditary Ataxias and Paraplegias and other International groups. RIBERMOV. EFACTS.

REDAPED (Spanish Registry of Degenerative Ataxias and Spastic Paraparesis).

Collaboration Agreement between ISCIII and SEN for the Development of Activities Related with the RDR within the activity field of SEN.

It was emphasized the significance of relationships with the Associations of Patients and their Relatives.

Hereditary ataxias and paraplegias

Designated CSUR (Reference Units)

Autonomous Region

Hospital U. La Fe Region Valenciana

Hospital U. La Paz Madrid

Hospitalario U. Marqués de Valdecilla

Cantabria

Hospital Clínico y Provincial de Barcelona

Cataluña

Hospital San Juan de Dios (Designated for children’s patients only)

Cataluña

Spanish Registry of Degenerative Ataxia and Spastic Paraparesis

(REDAPED)

1Hospital Universitario La Paz, Madrid; 2Hospital Universitario La Fe, Valencia; 3Hospital Josep Trueta, Girona; 4Institute Germans Trias i Pujol, Barcelona; 5Hospital Clinic, Barcelona; 6Hospital Sant Joan de Déu, Barcelona; 7Fundación Gallega de Medicina Genómica, Santiago de Compostela; 8Instituto Universitario Dexeus; 9Institut d'Investigació Biomèdica de Bellvitge, Barcelona; 10IIER

Arpa Gutiérrez, F.J.1; Bataller L.2; Genís Batlle D.3; Matilla Dueñas A.4; Muñoz J.E.5; O´Callaghan M.D.M.6; Pascual Pascual S.I.1; Quintáns Castro B.7; Sanz Gallego I.1; Serrano Munuera M.C.8; Sobrido Gómez M.J.7; Volpini Bertrán V.9; Posada M.10

Madrid, July 30, 2012

REDAPEDI. Promoters: Study Commission of Degenerative Ataxia

and Spastic Paraparesis (CEAPED) of the Spanish Society of Neurology (SEN)

Institute of Rare Diseases Research (IIER), Institute of Health Carlos III (ISCIII), Madrid.

 II. Scientific Committee: IIER (Manuel Posada de La Paz) SEN (F. Javier Arpa Gutiérrez) SENEP (Samuel Ignacio Pascual Pascual) NEUROGENES (Antoni Matilla Dueñas)

REDAPEDBACKGROUND. The Registry REDAPED will work in the context of

developing a comprehensive approach to health care for the Degenerative Ataxia and Spastic Paraparesis. It will include multidisciplinary activities to preserve the health, to maximize functional recovery and improve the quality of life of patients.

The prevalence of ataxias is variable and as soon as well-known, although it is assumed that it is fewer than 1 case per 1,000 population. In our experience it is 13.4/100,000 population (Aguilar-Amat et al, not published data).

The prevalence of HSPs has been considered between 1.27 and 9.6 per 100,000 population (Polo et al, 1991; Berciano et al, 2002; Fink, 2006, 2009).

REDAPEDWORK PLAN. The recruitment will be continuous. It is scheduled to carry out one inclusion visit and annual

monitoring visit. Data from other visits are also recorded when the patient

attends the hospital for reasons of disease’s impairment, complications or if the neurologist considers that it is necessary from the clinical point of view.

OBJECTIVES (I):  Main objective: The main objective of this project

consists in characterizing the patients with degenerative ataxias and spastic paraparesis on the basis of a minimum, specific and homogeneous collection of clinical and genetic data and recording it in an only REGISTRY pertaining to the Spanish Country.

REDAPEDOBJECTIVES (II): Secondary objectives:

The present research project will develop a network that comprise to many Spanish hospitals to recruit the greater number of patients with degenerative ataxia and spastic paraparesis clinically and, if it is possible, genetically defined.

The characterization of the patients will be supported on scales of clinical assessment, structural image, electrophysiology, cardiological evaluations and hematological data with the purpose of setting up the more extensive and better characterized collection of patients. These data will represent a great contribution to the knowledge of the natural history of the degenerative ataxias and spastic paraparesis.

A network will be created for these patients directed to provide them the information and to facilitate the contact with specialized neurological clinics.

Promote the multidisciplinary research excellence in ataxias and paraparesis.

Promote training on the study of the ataxias and paraparesis.

REDAPEDMETHODS (I). 1. Collection of data and information sources:

Clinical history and documents derived from this (case report form, databases previously elaborated by each one of the research groups, etc.).

The inclusion of genetic data will originate in the information of the genetics units / departments / institutes.

The data collection are comprised in a minimum set of data 2. Study population:

Degenerative Ataxias and Spastic Paraparesis Patients. It is planned to include around 10,000 patients in Spain.

3. Inclusion/exclusion criteria and withdrawal…

REDAPEDMETHODS (II). 4. Operational definition of variables (I):

Variables and information that will be collected in the Inclusion Visit: 1. Demographic data:

Gender Date of birth Ethnic group Birthplace Father birthplace Mother birthplace

2. Clinical history of Degenerative Ataxia or Spastic Paraparesis: Start date of disease Date of confirmed diagnosis Degenerative Ataxia or Spastic Paraparesis Type at Diagnosis Functional systems affected by the disease (cerebellar, pyramidal, brain

stem, sensory, sphincter, visual, auditory and mental) Genetics Concomitant diseases SARA scores at baseline (ataxias) and SPRS scores at baseline (Spastic

Paraparesis).

REDAPED

METHODS (III). 4. Operational definition of variables (II):

Variables and information that will be collected in the follow-up Visits: Visit date. Degenerative Ataxia or Spastic Paraparesis Type

according to the evolution Functional systems affected by the disease (cerebellar,

pyramidal, brain stem, sensory, sphincter, visual, auditory and mental)

New genetic data Concomitant diseases SARA scores at baseline (ataxias) and SPRS scores at

baseline (Spastic Paraparesis)

REDAPEDMETHODS (IV). 5. Planned sample size and the grounds for its

calculation. 6. Data management:

The regulations on the data management will be defined in the consortium agreement.

(SEN, IIER, SENEP, NEUROGENES y AEGH). The platform created for the RDR in ISCIII considers

the inclusion of massive data coming from AR (CCAA) and, at the same time, it will be able to include data coming from specific groups as CEAPED.

7. Data analysis. 8. Computer support:

The ISCIII platform guarantees the sustainability of the system and the associated legal issues.

SEN offers its resources to develop the design.

REDAPEDMETHODS (V). 9. Quality Assurance: The Scientific

Committee has as function the criteria management and the conflicts follow-up. Quality assurance should check the following standards:

a) Control of each included variableb) Validity of encoding c) Elaboration of indicators concerning contradictions between

the information of two combined variablesd) Process evaluatione) Control with external audits on the part of the own groupf) Analysis of the validity of the data The pertinent queries that assures the quality of

the data and the scientific accuracy of data collection in the electronic form software will be defined and implemented.

REDAPED ETHICAL ISSUES.1. Benefit-risk evaluation for those research subjects.2. Considerations about the information to patients and

family and informed consent (IC).3. Data Confidentiality.4. Interference with the doctor's prescribing habits. REGISTRY EXPLOITATION. PLANS FOR DISSEMINATION

OF RESULTS. By means of traditional forms of diffusion of information

whose copyright and signature models of publications will be captured in the consortium agreement

Elaboration of periodical reports in pdf format so that the different collaborating organizations in this project could spread basic information among their members

The way the different groups will be able to send data to European projects in course will be agreed.

All these points should be agreed and captured in the consortium agreement.

PROTOCOL AMENDMENTS.

REDAPEDPRACTICAL CONSIDERATIONS. 1. Follow-up information:

The promoters will send follow-up information to the Health Authorities with annual periodicity. They will be also notified any outstanding incidence occurring during the study (withdrawal, protocol amendments, etc.).

2. Diffusing results: The promoters are committed to publish the results of this

study in scientific journals.

ANNEXES Annex 1: Minimum Database of the Registry of

Degenerative Ataxia and Spastic Paraparesis (REDAPED). Annex 2: Informed Consent to the Patient. Annex 3: Form of Informed Consent. Annex 4: Classification of the Degenerative Ataxias. Annex 5: Classification of Hereditary Spastic or Familial

Spastic Paraparesis (HSP).

REDAPED

CONCLUSIONS: The main objective of the project REDAPED consists on

characterizing the patients with degenerative ataxias and spastic paraparesis.

The Registry REDAPED will contribute to develop the health care comprehensive approach of Ataxias and HSP, what include multidisciplinary interventions to preserve the health, to maximize the functional recovery and to improve the quality of life.

Full health care objectives will be achieved by means of continuous basic research, guided to understand the physiopathological mechanisms of Degenerative Ataxia and Spastic Paraparesis. REDAPED will promote these objectives.

REDAPED will promote the development of effective treatments to slow down, to stop, or even to revert the process of disease.

European Friedreich’s Ataxia Consortium for Translational Studies (EFACTS)

Scientific and technological objectives:1. Comprehensively populate a European FRDA database,

linked to a bio bank.2. Define a panel of clinical assessment tools that can be

used to define outcomes for clinical trials and identify the multiple health problems that occur during the course of FRDA disease progression.

3. Build on the knowledge base of frataxin structure and function.

4. Build on the knowledge base of frataxin-related cellular homeostasis and the pathogenic cascade.

5. Build on the knowledge base of epigenetic mechanisms regulating frataxin silencing.

6. Develop new and improved cellular and animal models for the study of FRDA.

7. Identify novel FRDA biomarkers.8. Identify genetic modifiers of FRDA disease.9. Develop novel therapeutic strategies for treating FRDA.

European Friedreich’s Ataxia Consortium for Translational

Studies (EFACTS)

Summary The EFACTS project will work towards developing a

global approach to FRDA care that will include multidisciplinary interventions to preserve health, maximize functional recovery and improve quality of life. This will be achieved through continued basic research into understanding the mechanisms of FRDA pathology, the creation of a European registry for FRDA and the development of effective treatments to slow, stop or even reverse the disease process. This will be done in continuous collaboration with patients’ associations (national associations and Euroataxia), involving the constant dissemination and education of EFACTS progress, to ultimately facilitate patient access to specialized centers where they can get the best of care.

RECRUITMENT IN SPAIN

•Total 56 patients•8 patients 1 year follow-up visit

Andalucía6

Extremadura4

Castilla la Mancha4

Castilla y León3 Cataluña

1

Madrid31

Valencia3

Aragón 3

Galicia1

COLLABORATION AGREEMENT BETWEEN THE INSTITUTE OF HEALTH CARLOS III AND THE SPANISH SOCIETY OF NEUROLOGY FOR THE

DEVELOPMENT OF ACTIVITIES RELATED TO RARE DISEASES REGISTRIES WITHIN THE ACTIVITY

FIELD OF THIS SOCIETY

Madrid, April 2012

D. Joaquín Roberto Arenas Barbero, Institute of Health Carlos III Director and Dr. Jerónimo Sancho Rieger,

President of the Spanish Society of Neurology

FOLLOW-UP AGREEMENT COMISSION

On the part of SEN Dr. F. Javier Arpa Gutiérrez Dr. Samuel Ignacio Pascual Pascual Dr. Susana Fernández Gómez

On the part of ISCIII Dr. Manuel Posada Dr. Ignacio Abaitua

ISSUES (1/FEB/2013): Review of the agreement Analysis of the state of the work done in the

field of ataxia and spastic paraparesis so far

Conclusions Improve the recognition of RD by neurologists Improve the information channels for neurologists Elaboration of a Map of the Spanish Health Care in RD Participate in clinical trials at home and abroad. Training courses in RD Collaboration with other Study Groups of SEN (Genetics,

Neuromuscular, Movement Disorders, General Neurology...), NEUROGENES Association, and other Medicine Specialties.

It is considered fundamental to maintain a close collaboration with CIBERER and CIBERNED. Translational Research.

Collaboration with European Groups of Hereditary Ataxias and Paraplegias and other International Groups.

Strengthen the Spanish RD registries of the Institute Carlos III Promote future registries (Ch-M-T, Neuromuscular, Dystonia,

treatable RD) Contribute to impel the genetic mutation’s database in RD Go more deeply into the Collaboration Agreement between ISCIII

and SEN for the Development of Activities Related with the RDR within the activity field of SEN.

Emphasize the significance of relationships with the Associations of Patients and their Relatives.

Thank you for your attentionThank you for your attention