Amantadine and Transcranial Magnetic Transcranial Magnetic Stimulation for Fatigue in Multiple Sclerosis: a Phase Iii, Controlled, Randomised, Double-Blind, Crossover Trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacion Para La Investigacion Biomedica Del Hospital Clinico San Carlos

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

28 Nov 2022 → ongoing

Decision date (initial)

2024-09-11

Transition trial

Yes

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-516732-97-00

EudraCT number

2021-004868-95

ClinicalTrials.gov

NCT05809414

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To compare the effect of TMS and amantadine alone or in combination therapy compared to placebo for treatment of fatigue in MS as determined by the MFIS scale. with placebo for the treatment of fatigue in MS as determined by the MFIS scale at 6 weeks

Secondary objectives 1

1. Changes in cognition, depression and quality of life will be assessed. For all of this, reference scales will be used that have been adequately validated for each of the objectives. A safety and cost-effectiveness analysis will also be carried out.

Conditions and MedDRA coding

multiple sclerosis (MS)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. Disability scale score (EDSS) at the time of recruitment (1, 5 to 4.5 points). 2. Fatigue Severity Scale (FSS) score greater than 4 points. 3. Beck Depression Inventory (BDI) score less than 30 points. 4. Not having presented an outbreak of the disease in at least three months prior to recruitment. recruitment. 5. Having undergone a four-week washout for any fatigue-related drugs related to fatigue: amantadine, modafinil, methylphenidate, acetyl-L-carnitine, cannabinol (delta-9-tetrahydrocannabinol, delta-9-tetrahydrocannabinol), cannabinol (delta-9-tetrahydrocannabinol and cannabidiol from Cannabis sativa L) and fampridine. fampridine. 6. Patient able to sign the Informed Consent form.

Exclusion criteria 1

1. 1. Patient diagnosed with a disease other than MS that may cause fatigue such as (but not limited to): a. Patient diagnosed with sleep apnoea treated with CPAP or not and who can justify fatigue apart from the disease. b. Patient with another associated autoimmune or rheumatological disease (lupus, rheumatoid arthritis...) that may justify the fatigue. In case of endocrine immune diseases, the patient is allowed to participate in the study if the analytical parameters are in range in the last 6 months and do not justify the fatigue. c. Patients with immune endocrine diseases. Inclusion is only allowed if the analytical parameters are in range in the last 6 months. d. Patients with diagnostic criteria for chronic fatigue syndrome. e. Patients with poorly controlled arterial hypertension or with decompensated, terminal or NYHA 3-4 heart failure. 2. Secondary epilepsy. 3. Present contraindications related to the treatments to be used (TMS or amantadine) such as: (a) Magnetically-sensitive metal on the head or within 12 inches (30.5 cm) of the TMS coil that cannot be removed. Objects that may contain such metal include: aneurysm clips or coils; carotid or cerebral stents; implanted stimulators; electrodes; ferromagnetic implants in the ears or eyes; bullets or shrapnel fragments; metal pellets, bullets or fragments; magnetically activated dental implants. b) History of epilepsy. c) Drugs that may lower the seizure threshold (antidepressants such as tricyclic antidepressants, antipsychotics, etc.). SSRIs are permitted at stable doses for the last 6 months. d) Hypersensitivity to amantadine. e) Severe heart disease, severe renal failure, angle-closure glaucoma. 4. Breast-feeding, pregnancy, or planning pregnancy in the next year. In case of fertile women, they must commit to the use of contraceptives throughout the study. In case of doubt at the time of inclusion, a pregnancy test will be performed. 5. Patients with a terminal medical illness with a life expectancy of less than one year. 6. Patient treated for malignant disease within the last three years. 7. Planning surgery during the trial period. 8. Any condition considered by the investigator team that may preclude participation/follow-up in the trial. 9. Alcohol or substance abuse within the past year. 10. Major psychiatric disorders (schizophrenia, schizoaffective disorders, bipolar, or obsessive-compulsive disorders, personality disorders). 11. Inability to communicate, poor command of the language or cognitive impairment that, in the opinion of the researcher, renders him/her incapable of carrying out the study. 12. Participation in another clinical trial with medication in the 4 months prior to inclusion. 13. Chronic use of drugs that may influence the results (unless they can be withdrawn prior to the start of the study): a. Antiepileptic drugs. Allowed in stable doses 3 months prior to inclusion. If it is necessary during the study because the patient has an epileptic seizure, it can be added. b. Diazepam and derivatives except in stable doses 3 months prior to inclusion. Modifications are permitted during the study. c. Baclofen, must be withdrawn with a period equal to or greater than 5 half-lives. d. SSRIs (Selective Serotonin Reuptake Inhibitors) except at stable doses 3 months prior to inclusion. If necessary during the study, may be added. e. Drugs that may lower the seizure threshold (antidepressants such as tricyclic antidepressants, antipsychotics, etc.). They are allowed in stable doses 3 months prior to inclusion. If necessary during the study, they can be added.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The change in the values of the MFIS questionnaire is considered as the main study variable for the evaluation of effectiveness.

Secondary endpoints 1

1. - Patient-perceived quality of life. The change in the mean score of the patient-perceived quality of life scale (SF-12) between the time of inclusion in the study and at the beginning and end of each phase will be assessed. - Beck Depression Inventory-II to assess depressive symptomatology. The assessment will be made at inclusion, and at the beginning and end of each phase. - Total costs per patient. Total costs of hospitalisation and treatment as well as other health care will be measured. -

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacion Para La Investigacion Biomedica Del Hospital Clinico San Carlos

Sponsor organisation

Fundacion Para La Investigacion Biomedica Del Hospital Clinico San Carlos

Address

Calle Del Profesor Martin Lagos

City

Madrid

Postcode

28040

Country

Spain

Scientific contact point

Organisation

Fundacion Para La Investigacion Biomedica Del Hospital Clinico San Carlos

Contact name

Jorge Matias-Guiu Guía

Public contact point

Organisation

Fundacion Para La Investigacion Biomedica Del Hospital Clinico San Carlos

Contact name

Jorge Matias-Guiu Guía

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 4 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications