Amantadine and Transcranial Magnetic Stimulation for Treating Fatigue in Multiple Sclerosis

NCT ID: NCT05809414

Last Updated: 2023-12-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

144 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-11-28

Study Completion Date

2025-02-28

Brief Summary

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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

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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

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Multiple Sclerosis Fatigue

Keywords

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Amantadine Multiple Sclerosis Fatigue Transcranial Magnetic Stimulation (TMS) Modified Fatigue Impact Scale (MFIS)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Amantadine

Group Type EXPERIMENTAL

Amantadine Hydrochloride 100 mg (milligrams) Oral Capsule

Intervention Type DRUG

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.

Placebo

Group Type PLACEBO_COMPARATOR

Amantadine Hydrochloride 100 mg (milligrams) Oral Capsule

Intervention Type DRUG

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.

TMS

Group Type EXPERIMENTAL

Transcranial Magnetic Stimulation

Intervention Type DEVICE

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.

TMS sham

Group Type SHAM_COMPARATOR

Transcranial Magnetic Stimulation

Intervention Type DEVICE

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.

Interventions

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Transcranial Magnetic Stimulation

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.

Intervention Type DEVICE

Amantadine Hydrochloride 100 mg (milligrams) Oral Capsule

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.

Intervention Type DRUG

Other Intervention Names

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TMS

Eligibility Criteria

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Inclusion Criteria

1. Expanded Disability Status Scale mark 1.5 - 4.5
2. Fatigue Severity Scale \> 4
3. Beck Depression Inventory \< 30
4. No relapse for, at least, three month prior to screening
5. Drug washout period = 4 weeks for any fatigue aimed drug
6. Patient capable to sign the informed consent

Exclusion Criteria

1. Fatigue causing disease other than multiple sclerosis:

1. sleep apnea
2. other autoimmune disease that could be explain the fatigue.
3. endocrine autoimmune disease if the blood test is not in range in the last 6 month.
4. patient with diagnosis of chronic fatigue
5. Patient with high blood pressure out of range or decompensated heart failure or New York Heart Association (NYHA) 3-4.
2. Secondary Epilepsy or neuropathic chronic pain which requires continuous treatment.
3. Contraindication for trial treatment:

1. Some kind of magnetic metal.
2. Epilepsy antecedents.
3. Any drugs that could decrease the seizure threshold
4. Amantadine sensitivity
5. Cardiopathy disease, severe kidney failure, Angle-closure glaucoma
4. 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.
5. Patient with a terminal disease with no more than one year life expectancy.
6. Patient has been treated for a maligned disease in the past three years.
7. A scheduled surgery in the course of the trials.
8. Any condition that a member of research team consider could affect to participation/follow up patient.
9. Alcoholic o toxics condition in the last year.
10. Major mental disorders
11. Poor communication skills or poor cognitive condition.
12. Other trial participation in the previous 4 month.
13. Use a chronic drug that could interfere in the clinical outcome.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hospital San Carlos, Madrid

OTHER

Sponsor Role lead

Responsible Party

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Jorge Matías-Guiu

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Jorge Matias-Guiu Guia, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Hospital San Carlos, Madrid

Locations

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Hospital Puerta del Mar

Cadiz, , Spain

Site Status RECRUITING

Hospital General Gregorio Marañon

Madrid, , Spain

Site Status RECRUITING

Hospital Clínico San Carlos

Madrid, , Spain

Site Status RECRUITING

Hospitalario Universitario Nuestra Señora de la Candelaria

Santa Cruz de Tenerife, , Spain

Site Status RECRUITING

Countries

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Spain

Central Contacts

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Jorge Matias-Guiu Guia, MD PhD

Role: CONTACT

Phone: +34 913303000

Email: [email protected]

Jordi Matias-Guiu Antem, MD PhD

Role: CONTACT

Phone: +34 913303000

Email: [email protected]

Facility Contacts

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Lucía Forero Díaz, MD PhD

Role: primary

María Luisa Martínez Ginés, MD PhD

Role: primary

Jorge Matias-Guiu Guia, MD PhD

Role: primary

Miguel Ángel Hernández Pérez, MD PhD

Role: primary

References

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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.

Reference Type DERIVED
PMID: 38176857 (View on PubMed)

Other Identifiers

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FETEM

Identifier Type: -

Identifier Source: org_study_id