Multiple SclerosisPhase 3FETEMNCT05809414
Amantadine and Transcranial Magnetic Stimulation for Treating Fatigue in Multiple Sclerosis
A Phase 3 study testing Transcranial Magnetic Stimulation and Amantadine Hydrochloride 100 mg (milligrams) Oral Capsule in people with Multiple Sclerosis and Fatigue, run by Hospital San Carlos, Madrid at 4 sites in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Sclerosis, Fatigue
- What is being tested?
- Transcranial Magnetic Stimulation and Amantadine Hydrochloride 100 mg (milligrams) Oral Capsule
- Type of treatment
- Pill or oral medicine, Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 144 participants
- Where
- 4 sitesSpain
- Study dates
- 28 Nov 2022to 28 Feb 2025
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 23Show fewer
- 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.
- Patient has been treated for a maligned disease in the past three years.
- A scheduled surgery in the course of the trials.
- Any condition that a member of research team consider could affect to participation/follow up patient.
- Alcoholic o toxics condition in the last year.
- Major mental disorders
- Poor communication skills or poor cognitive condition.
- Other trial participation in the previous 4 month.
- Use a chronic drug that could interfere in the clinical outcome.
Trial locations and contacts
4 sites in 1 country.
Spain4 sites, 4 recruiting
- Recruiting
Hospital Puerta del Mar
Cadiz, 11009
Lucía Forero Díaz, MD PhD, lucia.forero.diaz@hotmail.es
- Recruiting
Hospital General Gregorio Marañon
Madrid, 28007
María Luisa Martínez Ginés, MD PhD, marisamgines@hotmail.com
- Recruiting
Hospital Clínico San Carlos
Madrid, 28040
Jorge Matias-Guiu Guia, MD PhD, matiasguiu@gmail.com
Jorge Matias-Guiu Guia, MD PhD
- Recruiting
Hospitalario Universitario Nuestra Señora de la Candelaria
Santa Cruz de Tenerife, 38010
Miguel Ángel Hernández Pérez, MD PhD, mhernandezp78@hotmail.com
About this study
Official title: Amantadine and Transcranial Magnetic Stimulation for Treating Fatigue in Multiple Sclerosis: Phase III Study, Controlled, Randomized, Crossed Over and Double Blind.
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.
Read the detailed description
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.
The main objective of the study is to evaluate the change in the severity of fatigue in MS patients undergoing treatment with amantadine, TMS and both in combination, compared to placebo. A randomized, placebo-controlled, crossover, double-blind clinical trial will be conducted. As secondary objectives, changes in cognition, depression and quality of life will be evaluated. For all this, the reference scales adequately validated for each of the objectives will be used.
- Conditions
- Multiple Sclerosis, Fatigue
- Being tested
- Transcranial Magnetic Stimulation, Amantadine Hydrochloride 100 mg (milligrams) Oral Capsule
- Keywords
- Amantadine, Multiple Sclerosis, Fatigue, Transcranial Magnetic Stimulation (TMS), Modified Fatigue Impact Scale (MFIS)
- Medical subject headings
- Multiple Sclerosis, Fatigue
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcranial Magnetic StimulationDevice
Also called TMS
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.
Amantadine Hydrochloride 100 mg (milligrams) Oral CapsuleDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Amantadine | Experimental | Not described Receives: Drug: Amantadine Hydrochloride 100 mg (milligrams) Oral Capsule |
| Placebo | Placebo comparator | Not described Receives: Drug: Amantadine Hydrochloride 100 mg (milligrams) Oral Capsule |
| TMS | Experimental | Not described Receives: Device: Transcranial Magnetic Stimulation |
| TMS sham | Sham comparator | Not described Receives: Device: Transcranial Magnetic Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 6 weeks after starting treatment
Secondary outcomes (5)
To assess the cognitive condition
To compare the effect of TMS and amantadine alone or in combination therapy compared to placebo on cognition determined by the Symbol Digit Modalities Test (SDMT).
Measured: 6 weeks after starting treatment
To assess the depression condition
To compare the effect of TMS and amantadine alone or in combination therapy compared to placebo on depression measured using the Beck Depression Inventory Scale (BDI-II score: Range from 0 to 63, from minimal to severe depression).
Measured: 6 weeks after starting treatment
To assess the quality of life
To compare the effect of TMS and amantadine alone or in combination therapy compared to placebo on the quality of life determined by the Short Form 12 Mental Health scale (SF-12 score: Range from 0 to 100, from worse to better physical and mental health functioning).
Measured: 6 weeks after starting treatment
Safety assessment
Analyze the incidence of the adverse events detected in each of the branches, whether or not with multiple sclerosis
Measured: 6 months after randomization
Cost-effectivity assessment
Determine the cost-effectiveness of the different interventions. The total costs of hospitalization and treatment, as well as other health care, will be measured.
Measured: 6 weeks after starting treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2023
- Study start28 Nov 2022
- Primary completion15 Jul 2024 (estimated)
- Study completion28 Feb 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- All patients will receive all possible combinations (TMS+placebo, TMS+amantadine, TMS sham+amantadine, TMS sham+placebo), the only difference being the sequence in which they are administered.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 144 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospital San Carlos, Madrid
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jorge Matías-Guiu, Hospital San Carlos, Madrid
- Investigators
- Jorge Matias-Guiu Guia, MD PhD, Principal investigator, Hospital San Carlos, Madrid
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05809414
- Sponsor's protocol ID
- FETEM
- Acronym
- FETEM
- Status last verified
- Dec 2023
- First submitted
- 20 Mar 2023
- Last updated
- 11 Dec 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 38176857
Study at a glance
From the registry record, last updated by the sponsor on 11 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Amantadine and Transcranial Magnetic Stimulation for Treating Fatigue in Multiple Sclerosis: Phase III Study, Controlled, Randomized, Crossed Over and Double Blind.
- ClinicalTrials.gov ID
- NCT05809414
- Acronym / sponsor ID
- FETEM / FETEM
- Conditions
- Multiple Sclerosis, Fatigue
- Keywords
- Amantadine, Multiple Sclerosis, Fatigue, Transcranial Magnetic Stimulation (TMS), Modified Fatigue Impact Scale (MFIS)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 144 participants (estimated)
- Lead sponsor
- Hospital San Carlos, MadridUniversity, hospital or other
- Study start
- 28 Nov 2022 (actual)
- Primary completion
- 15 Jul 2024 (estimated)
- Study completion
- 28 Feb 2025 (estimated)
- First posted
- 12 Apr 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
The main objective of the study is to evaluate the change in the severity of fatigue in MS patients undergoing treatment with amantadine, TMS and both in combination, compared to placebo. A randomized, placebo-controlled, crossover, double-blind clinical trial will be conducted. As secondary objectives, changes in cognition, depression and quality of life will be evaluated. For all this, the reference scales adequately validated for each of the objectives will be used.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- All patients will receive all possible combinations (TMS+placebo, TMS+amantadine, TMS sham+amantadine, TMS sham+placebo), the only difference being the sequence in which they are administered.
| Arm | Type | Receives |
|---|---|---|
| Amantadine | Experimental | Drug: Amantadine Hydrochloride 100 mg (milligrams) Oral Capsule |
| Placebo | Placebo comparator | Drug: Amantadine Hydrochloride 100 mg (milligrams) Oral Capsule |
| TMS | Experimental | Device: Transcranial Magnetic Stimulation |
| TMS sham | Sham comparator | Device: Transcranial Magnetic Stimulation |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (23 listed)
- Fatigue causing disease other than multiple sclerosis:
- Secondary Epilepsy or neuropathic chronic pain which requires continuous treatment.
- Contraindication for trial treatment:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Transcranial Magnetic StimulationAlso: TMSTMS 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. | Device | TMS, TMS sham |
| Amantadine Hydrochloride 100 mg (milligrams) Oral CapsuleIt 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. | Drug | Amantadine, Placebo |
Primary outcome
To assess the fatigue severity
Time frame: 6 weeks after starting treatment
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).
5 secondary outcomes
To assess the cognitive condition
Time frame: 6 weeks after starting treatment
To assess the depression condition
Time frame: 6 weeks after starting treatment
To assess the quality of life
Time frame: 6 weeks after starting treatment
Safety assessment
Time frame: 6 months after randomization
Cost-effectivity assessment
Time frame: 6 weeks after starting treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Dec 2023.
- Derived from this study: PubMed 38176857Matias-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.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jorge Matias-Guiu Guia, MD PhD principal investigator
Hospital San Carlos, Madrid
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Transcranial Magnetic Stimulation and Amantadine Hydrochloride 100 mg (milligrams) Oral Capsule in people with Multiple Sclerosis and Fatigue, run by Hospital San Carlos, Madrid at 4 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 11 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jorge Matias-Guiu Guia, MD PhD (+34 913303000 ext. 3511, matiasguiu@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To assess the fatigue severity (time frame: 6 weeks after starting treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05809414, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Dec 2023.