Using Amantadine and TMS to Treat Fatigue in Multiple Sclerosis

Amantadine and Transcranial Magnetic Stimulation for Treating Fatigue in Multiple Sclerosis: Phase III Study, Controlled, Randomized, Crossed Over and Double Blind.

This study is testing whether the combination of a medication called amantadine and a treatment called TMS can help reduce fatigue in people with multiple sclerosis.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 144 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Hospital San Carlos, Madrid (other)
• Locations: 4 sites (Cadiz and 3 other locations)
• Trial ID: NCT05809414 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the effectiveness of amantadine, transcranial magnetic stimulation (TMS), and their combination in reducing fatigue among patients with multiple sclerosis (MS). It is a randomized, placebo-controlled, crossover, double-blind study that will assess changes in fatigue severity, cognition, depression, and quality of life using validated scales. The trial seeks to provide a more effective treatment option for a common and debilitating symptom of MS, which currently lacks adequate therapeutic solutions.

Who should consider this trial

Good fit: Ideal candidates for this study are adults with multiple sclerosis experiencing significant fatigue, as indicated by specific eligibility criteria.

Not a fit: Patients with fatigue due to conditions other than multiple sclerosis or those with contraindications to the trial treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new effective treatment for fatigue in patients with multiple sclerosis.

How similar studies have performed: Preliminary studies have suggested that TMS may be beneficial for treating fatigue in MS, but this approach has not been adequately tested in large-scale trials.

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.

Where this trial is running

Cadiz and 3 other locations

• Hospital Puerta del Mar — Cadiz, Spain (RECRUITING)
• Hospital General Gregorio Marañon — Madrid, Spain (RECRUITING)
• Hospital Clínico San Carlos — Madrid, Spain (RECRUITING)
• Hospitalario Universitario Nuestra Señora de la Candelaria — Santa Cruz De Tenerife, Spain (RECRUITING)

Study contacts

• Principal investigator: Jorge Matias-Guiu Guia, MD PhD — Hospital San Carlos, Madrid
• Study coordinator: Jorge Matias-Guiu Guia, MD PhD

Conditions: Multiple Sclerosis, Fatigue, Amantadine, Transcranial Magnetic Stimulation, Modified Fatigue Impact Scale