Amantadine and Transcranial Magnetic Stimulation for Treating Fatigue in Multiple Sclerosis
FETEM
1 other identifier
interventional
144
1 country
4
Brief Summary
Multiple Sclerosis (MS) is the most frequent cause of non-traumatic disability in people under 55 years of age. Fatigue is the most frequent and disabling symptom in the disease, and for which there is no effective treatment. Among the proposed drugs, amantadine is the one that could be most useful, although up to now it has not been adequately demonstrated due to a lack of sufficiently powerful and methodologically appropriate clinical trials. Transcranial magnetic stimulation (TMS) has recently been proposed as a useful treatment for fatigue in MS in preliminary studies.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3 multiple-sclerosis
Started Nov 2022
4 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
November 28, 2022
CompletedFirst Submitted
Initial submission to the registry
March 20, 2023
CompletedFirst Posted
Study publicly available on registry
April 12, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 15, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
February 28, 2025
CompletedDecember 11, 2023
December 1, 2023
1.6 years
March 20, 2023
December 4, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
To assess the fatigue severity
To compare the effect of TMS and amantadine alone or in combination therapy compared with placebo on fatigue determined using the Modified Fatigue Impact Scale (Total MFIS score: Range from 0 to 84, from minimal to severe fatigue).
6 weeks after starting treatment
Secondary Outcomes (5)
To assess the cognitive condition
6 weeks after starting treatment
To assess the depression condition
6 weeks after starting treatment
To assess the quality of life
6 weeks after starting treatment
Safety assessment
6 months after randomization
Cost-effectivity assessment
6 weeks after starting treatment
Study Arms (4)
Amantadine
EXPERIMENTALPlacebo
PLACEBO COMPARATORTMS
EXPERIMENTALTMS sham
SHAM COMPARATORInterventions
TMS is a technique for electrical stimulation of brain tissue by generating a magnetic field, which modulates neural activity at the stimulation site and in interconnected neural networks. The treatment will be applied to the left dorsolateral prefrontal region. Each patient will receive 3 sessions per week of approximately 10 minutes for 6 weeks. In the case of TMS sham, a placebo coil will be used, which is indistinguishable from the therapeutic one. In addition, the sessions will be carried out with the same frequency, so the patient will be unaware of the treatment they are receiving.
It will be used at a dose of 100 mg, 1 capsule a day for 1 week, followed by 2 daily doses of 100 mg until completing 6 weeks in total. After completing the treatment phase, the dose will be de-escalated (1 capsule a day for 5 days and discontinued). In the case of placebo amantadine capsules, they will have the same organoleptic characteristics as amantadine. The start, maintenance and de-escalation pattern will be identical.
Eligibility Criteria
You may qualify if:
- Expanded Disability Status Scale mark 1.5 - 4.5
- Fatigue Severity Scale \> 4
- Beck Depression Inventory \< 30
- No relapse for, at least, three month prior to screening
- Drug washout period = 4 weeks for any fatigue aimed drug
- Patient capable to sign the informed consent
You may not qualify if:
- Fatigue causing disease other than multiple sclerosis:
- sleep apnea
- other autoimmune disease that could be explain the fatigue.
- endocrine autoimmune disease if the blood test is not in range in the last 6 month.
- patient with diagnosis of chronic fatigue
- Patient with high blood pressure out of range or decompensated heart failure or New York Heart Association (NYHA) 3-4.
- Secondary Epilepsy or neuropathic chronic pain which requires continuous treatment.
- Contraindication for trial treatment:
- Some kind of magnetic metal.
- Epilepsy antecedents.
- Any drugs that could decrease the seizure threshold
- Amantadine sensitivity
- Cardiopathy disease, severe kidney failure, Angle-closure glaucoma
- Breastfeeding, pregnancy, or pregnancy planning phase in the next year. Of childbearing potential and willing to use an acceptable method of contraception during the study period.
- Patient with a terminal disease with no more than one year life expectancy.
- +8 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (4)
Hospital Puerta del Mar
Cadiz, 11009, Spain
Hospital General Gregorio Marañon
Madrid, 28007, Spain
Hospital Clínico San Carlos
Madrid, 28040, Spain
Hospitalario Universitario Nuestra Señora de la Candelaria
Santa Cruz de Tenerife, 38010, Spain
Related Publications (1)
Matias-Guiu JA, Gonzalez-Rosa J, Hernandez MA, Martinez-Gines ML, Portoles A, Perez-Macias N, Benito-Leon J, Padron I, Prieto J, Matias-Guiu J. 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. BMJ Open. 2024 Jan 4;14(1):e078661. doi: 10.1136/bmjopen-2023-078661.
PMID: 38176857DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Jorge Matias-Guiu Guia, MD PhD
Hospital San Carlos, Madrid
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- CROSSOVER
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
March 20, 2023
First Posted
April 12, 2023
Study Start
November 28, 2022
Primary Completion
July 15, 2024
Study Completion
February 28, 2025
Last Updated
December 11, 2023
Record last verified: 2023-12
Data Sharing
- IPD Sharing
- Will share
The data used will be deposited in a suitable repository that will be complied with the requirements of ISCIII and any other applicable national regulations. Due to the data collected retain their personal character and they can be traced back, they will be safeguarded maintaining their integrity and confidentiality. These data cannot be openly shared after the project's completion. The licenses and access permissions will be determined based on the following criteria before the project's completion: a) The guidelines or recommendations of ISCIII. b) The policies established by the data repository to which the data will be sent. c) Possible restrictions on data publication that may arise from applicable protection schemes for the project's results. In any case, the requirements set forth by ISCIII in the funding call received will be complied with, as well as those considered in other applicable regulations. The dataset used will be stored in a locked condition for a period of 5 years.