Clinical trial NCT05809414: Amantadine and Transcranial Magnetic Stimulation for Treating Fatigue in Multiple Sclerosis
Official title: Amantadine and Transcranial Magnetic Stimulation for Treating Fatigue in Multiple Sclerosis: Phase III Study, Controlled, Randomized, Crossed Over and Double Blind.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Multiple Sclerosis
Fatigue
Keywords: Amantadine
Multiple Sclerosis
Fatigue
Transcranial Magnetic Stimulation (TMS)
Modified Fatigue Impact Scale (MFIS)
Lead sponsor: Hospital San Carlos, Madrid
Sponsor class: OTHER
First posted: 2023-04-12
Enrollment: 144
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention 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.
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: To assess the fatigue severity
timeFrame: 6 weeks after starting treatment
Secondary outcomes:
measure: To assess the cognitive condition
timeFrame: 6 weeks after starting treatment
measure: To assess the depression condition
timeFrame: 6 weeks after starting treatment
measure: To assess the quality of life
timeFrame: 6 weeks after starting treatment
measure: Safety assessment
timeFrame: 6 months after randomization
measure: Cost-effectivity assessment
timeFrame: 6 weeks after starting treatment
Other outcomes:
Locations:
city: Cadiz
country: Spain
facility: Hospital Puerta del Mar
city: Madrid
country: Spain
facility: Hospital General Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Santa Cruz De Tenerife
country: Spain
facility: Hospitalario Universitario Nuestra Señora de la Candelaria
Study officials:
affiliation: Hospital San Carlos, Madrid
name: Jorge Matias-Guiu Guia, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: