Amantadine and/or transcranial magnetic stimulation for fatigue associated with multiple sclerosis (FETEM): study protocol for a phase 3 randomised, double-blind, cross-over, controlled clinical trial

  1. Jordi A Matias-Guiu 27
  2. Javier González-Rosa 101112
  3. Miguel Ángel Hernández 16
  4. Maria Luisa Martínez-Ginés 56
  5. Antonio Portolés 1234
  6. Natalia Pérez-Macías 34
  7. Julián Benito-León 513
  8. Iván Padrón 89
  9. Julio Prieto 1415
  10. Jorge Matias-Guiu 27
  1. 1 Department of Pharmacology and Toxicology
  2. 2 Universidad Complutense de Madrid
    info

    Universidad Complutense de Madrid

    Madrid, España

    ROR 02p0gd045

  3. 3 Unidad de Investigación Clínica y Ensayos Clínicos (UICEC)
  4. 4 Instituto de Investigacion Sanitaria Hospital Clinico San Carlos
  5. 5 Department of Neurology
  6. 6 Hospital Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM)
  7. 7 Department of Neurology, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISCC)
  8. 8 Department of Developmental Psychology and Education, Instituto Universitario de Neurociencia (IUNE)
  9. 9 Universidad de La Laguna
    info

    Universidad de La Laguna

    San Cristobal de La Laguna, España

    ROR https://ror.org/01r9z8p25

  10. 10 Department of Psychology
  11. 11 Universidad de Cádiz
    info

    Universidad de Cádiz

    Cádiz, España

    ROR https://ror.org/04mxxkb11

  12. 12 Institute of Research and Biomedical Innovation of Cadiz
  13. 13 Hospital Universitario 12 de Octubre, Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), Universidad Complutense
  14. 14 Department of Clinical Neurophysiology
  15. 15 Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM)
  16. 16 Hospital Universitario Nuestra Señora de la Candelaria
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Revista:
BMJ Open

ISSN: 2044-6055

Año de publicación: 2024

Volumen: 14

Número: 1

Páginas: e078661

Tipo: Artículo

DOI: 10.1136/BMJOPEN-2023-078661 GOOGLE SCHOLAR lock_openAcceso abierto editor

Otras publicaciones en: BMJ Open

Resumen

Introduction Fatigue is one of the most disabling symptoms of multiple sclerosis (MS), and effective treatments are lacking. Amantadine is one of the most used treatments, although its efficacy is under debate. Transcranial magnetic stimulation (TMS) is a promising intervention that has shown positive effects in some preliminary investigations. We aim to investigate the effect of 6 weeks of amantadine and/or TMS in fatigue due to MS.Methods and analysis The study is a national, multicentre, phase 3, randomised, double-blind, cross-over, placebo-controlled and sham-controlled clinical trial. Adult patients with relapsing-remitting MS, Expanded Disability Status Scale score of 1.5–4.5 and Fatigue Severity Score>4 are eligible for the trial. Participants will be randomised to one of the sequences of the study. Each sequence consists of four periods of 6 weeks of treatment and three washout periods of 12–18 weeks. All patients will receive all the combinations of therapies. The primary outcome is the Modified Fatigue Impact Scale. The secondary outcomes are the Symbol Digit Modalities Test (cognition), Beck Depression Inventory-II (depressive symptoms) and Short-Survey 12 (quality of life). Safety and cost-effectiveness will also be evaluated. An exploratory substudy including MRI and blood biomarkers will be conducted.Ethics and dissemination The study is approved by the Ethics Committee of the Hospital Clinico San Carlos and the Spanish Agency of Medications and Medical Devices. All study findings will be published in scientific peer-reviewed journals and presented at relevant scientific conferences.Trial registration number EudraCT 2021-004868-95; [NCT05809414][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT05809414&atom=%2Fbmjopen%2F14%2F1%2Fe078661.atom