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Clinical Trials/NCT05809414
NCT05809414
Recruiting
Phase 3

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

Hospital San Carlos, Madrid4 sites in 1 country144 target enrollmentNovember 28, 2022

Overview

Phase
Phase 3
Intervention
Amantadine Hydrochloride 100 mg (milligrams) Oral Capsule
Conditions
Multiple Sclerosis
Sponsor
Hospital San Carlos, Madrid
Enrollment
144
Locations
4
Primary Endpoint
To assess the fatigue severity
Status
Recruiting
Last Updated
2 years ago

Overview

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.

Registry
clinicaltrials.gov
Start Date
November 28, 2022
End Date
February 28, 2025
Last Updated
2 years ago
Study Type
Interventional
Study Design
Crossover
Sex
All

Investigators

Responsible Party
Principal Investigator
Principal Investigator

Jorge Matías-Guiu

Principal Investigator

Hospital San Carlos, Madrid

Eligibility Criteria

Inclusion Criteria

  • 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

Exclusion Criteria

  • 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-
  • Secondary Epilepsy or neuropathic chronic pain which requires continuous treatment.
  • Contraindication for trial treatment:
  • Some kind of magnetic metal.
  • Epilepsy antecedents.

Arms & Interventions

Amantadine

Intervention: Amantadine Hydrochloride 100 mg (milligrams) Oral Capsule

Placebo

Intervention: Amantadine Hydrochloride 100 mg (milligrams) Oral Capsule

TMS

Intervention: Transcranial Magnetic Stimulation

TMS sham

Intervention: Transcranial Magnetic Stimulation

Outcomes

Primary Outcomes

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).

Secondary Outcomes

  • To assess the depression condition(6 weeks after starting treatment)
  • Cost-effectivity assessment(6 weeks after starting treatment)
  • To assess the cognitive condition(6 weeks after starting treatment)
  • Safety assessment(6 months after randomization)
  • To assess the quality of life(6 weeks after starting treatment)

Study Sites (4)

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