NCT04062331

Brief Summary

Background: Transcranial Magnetic Stimulation (TMS) is a technique based on the principles of electromagnetic induction. It applies pulses of magnetic radiation that penetrate the brain tissue, and it is a non-invasive, painless and practically innocuous procedure. Previous studies advocate the therapeutic capacity of TMS in several neurodegenerative and psychiatric processes, both in animal models and in human studies. Its uses in Parkinson's disease, Alzheimer's disease and in Huntington's chorea have shown improvement in the symptomatology and in the molecular profile, and even in the cellular density of the brain. Consequently, the extrapolation of these TMS results in the aforementioned neurodegenerative disease to other entities with etiopathogenic and clinical analogy would raise the relevance and feasibility of its use in multiple sclerosis (MS). The overall objective will be to demonstrate the effectiveness of the TMS in terms of safety and clinical improvement, as well as to observe the molecular changes in relation to the treatment. Methods and design: Phase I clinical trial, unicentric, controlled, randomised, single blind. A total of 90 patients diagnosed with relapsing-remitting multiple sclerosis (RRMS) who meet all the inclusion criteria and do not present any of the exclusion criteria that are established and from which clinically evaluable results can be obtained. The patients included will be assigned under the 1:1:1 randomization formula, constituting three groups for the present study: 30 patients treated with natalizumab + white (placebo) + 30 patients treated with natalizumab + TMS (1 Hertz) + 30 patients treated with natalizumab + TMS (5 Hertz). Discussion: Results of this study will inform on the efficiency of the TMS for the treatment of MS. The expected results are that TMS is a useful therapeutic resource to improve clinical status (main parameters) and neurochemical profile (surrogate parameters); both types of parameters will be checked.

Trial Health

35
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
90

participants targeted

Target at P75+ for phase_1 multiple-sclerosis

Timeline
Completed

Started Oct 2019

Typical duration for phase_1 multiple-sclerosis

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 1, 2019

Completed
19 days until next milestone

First Posted

Study publicly available on registry

August 20, 2019

Completed
1 month until next milestone

Study Start

First participant enrolled

October 1, 2019

Completed
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2021

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2022

Completed
Last Updated

August 21, 2019

Status Verified

August 1, 2019

Enrollment Period

2 years

First QC Date

August 1, 2019

Last Update Submit

August 19, 2019

Conditions

Keywords

clinical trialmultiple sclerosisneurodegenerative diseasestranscranial magnetic stimulationdeep brain stimulationneurochemistry

Outcome Measures

Primary Outcomes (3)

  • Clinical activity of the disease

    Expanded Disability Status Scale. Score from 0 (total absence of disability) to 10 (death due to multiple sclerosis).

    up 1 year

  • Comprehensive clinical assessment of the disease

    Multiple Sclerosis Functional Composite. It consists of three tests: Timed 25-Foot Walk, 9-Hole Peg Test and Paced Auditory Serial Addition Task. Score measured as a function of time. The higher, the worse the patient's condition.

    up 1 year

  • Cognitive function

    Brief Repeatable Battery of Neuropsychological Test. It consists of the selective reminding test, the 10/36 spatial recall test, the symbol digit modalities test, the paced auditory serial addition test and the word list generation test. A higher score means a better status in a person.

    up 1 year

Secondary Outcomes (12)

  • Assessment of fatigue

    up 1 year

  • Depression assessment

    up 1 year

  • Image analysis

    through study completion, an average of 1 year

  • Lipoperoxidation molecules

    through study completion, an average of 1 year

  • Carbonylated proteins

    through study completion, an average of 1 year

  • +7 more secondary outcomes

Study Arms (3)

Placebo group

PLACEBO COMPARATOR

This group will be under standard therapy (natalizumab) plus Transcranial Magnetic Stimulation (TMS) without any frequency (device doesn't running; it means, device turned off) but the same duration of sessions.

Drug: Placebos

Group under TMS 1 Hertz treatment

EXPERIMENTAL

1 Hertz group (1 Hertz ) will be under standard therapy (natalizumab) plus Transcranial Magnetic Stimulation (TMS) running with a frequency of 1 Hertz.

Device: Transcranial Magnetic Stimulation (TMS)

Group under TMS 5 Hertz treatment

EXPERIMENTAL

5 Hertz group (5 Hertz ) will be under standard therapy (natalizumab) plus Transcranial Magnetic Stimulation (TMS) running with a frequency of 5 Hertz .

Device: Transcranial Magnetic Stimulation (TMS)

Interventions

By means of the magnetic stimulator we induce a cerebral electric current that is able to obtain a motor potential in the first dorsal interosseous bone of the left hand. The intervention procedure consists of two steps: First step: Obtaining the Motor Evoked Threshold at Rest: Each patient, regardless of to the group to which they belong will have his/her threshold evoked motor calculated at rest, by stimulation of the right motor cortex, evoking electromyographic responses in the contralateral muscles. Second step: Administration of TMS: To calculate the motive threshold as the percentage of the same to which the treatment will have to be applied, a device equipped with a coil. The treatment will be administered for 5 consecutive days, with 3 weeks of rest, between each stimulation. To complete a treatment period of 14 months. The stimulation with TMS will be carried out every day in the same time slot for 5 consecutive days every 4 weeks, during a period of 14 months.

Also known as: Deep Brain Stimulation, Deep Transcranial Magnetic Stimulation
Group under TMS 1 Hertz treatmentGroup under TMS 5 Hertz treatment

Administration of Transcranial Magnetic Stimulation at 0 Hz (the patient will be only under drug standar therapy)

Also known as: Sham group
Placebo group

Eligibility Criteria

Age14 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Patients diagnosed with RRMS in their inflammatory forms who have completed a 14-dose treatment with natalizumab.
  • Normal analytical parameters, defined by: Leukocytes\> 3000 / mcl, Neutrophils\> 1500 / mcl, Platelets\> 100000 / mcl, AST/ALT \<2.5 IU / L, Creatinine \<2.5 mg / dl.
  • Patients of both sexes aged between 18 and 60 years.
  • EDSS: between 3.0 and 6.5 points.
  • Patients who give their informed consent for participation in the clinical trial.

You may not qualify if:

  • Any active or chronic infection, including HIV infection, or hepatitis B or C.
  • History of neoplasia (basal cell carcinoma of the skin and in situ carcinoma in remission are excluded for more than one year).
  • Life expectancy severely limited by other co-morbidities.
  • Endocrine disease such as diabetes, hyper or hypothyroidism.
  • Chronic inflammatory or autoimmune disease such as ulcerative colitis, Crohn's disease, systemic lupus erythematosus and any other form of connective tissue disease or chronic arthropathy.
  • Chronic obstructive pulmonary disease.
  • Severe psychiatric illnesses.
  • Hepatic, or renal, or cardiac dysfunction (including coronary heart disease and heart failure).
  • Chronic anaemia.
  • Pregnancy or risk of pregnancy (including refusal to use contraception).
  • Women in breastfeeding period.
  • Inability to undergo MRI scans.
  • Inability to grant written informed consent.
  • Taking lipid-lowering drugs and vitamin supplements.
  • Treatment with steroids and/or non-steroidal anti-inflammatories, or alcohol intake 40 hours before the blood extraction and/or development of the different tests.
  • +3 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (1)

  • Aguera E, Caballero-Villarraso J, Feijoo M, Escribano BM, Conde C, Bahamonde MC, Giraldo AI, Paz-Rojas E, Tunez I. Clinical and Neurochemical Effects of Transcranial Magnetic Stimulation (TMS) in Multiple Sclerosis: A Study Protocol for a Randomized Clinical Trial. Front Neurol. 2020 Aug 11;11:750. doi: 10.3389/fneur.2020.00750. eCollection 2020.

MeSH Terms

Conditions

Multiple SclerosisNeurodegenerative Diseases

Interventions

Transcranial Magnetic StimulationDeep Brain Stimulation

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNSAutoimmune Diseases of the Nervous SystemNervous System DiseasesDemyelinating DiseasesAutoimmune DiseasesImmune System Diseases

Intervention Hierarchy (Ancestors)

Magnetic Field TherapyTherapeuticsElectric Stimulation TherapySurgical Procedures, Operative

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
Masking Details
Single-blind. Investigator who applies transcranial stimulation knows the kind of treatment (placebo, TMS 1 Hertz, TMS 5 Hertz). The patients don't know the frequency (measured Hertz) which TMS is running (0 Hertz= placebo, 1 Hertz, 5 Hertz) and the device and duration of sessions are the same.
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Phase I clinical trial, unicentric, controlled, randomised, single blind. Three arms. The patients included will be assigned under the 1:1:1 randomization formula, constituting three groups for the present study: 30 patients treated with natalizumab + white (placebo) + 30 patients treated with natalizumab + TMS (1 Hertz) + 30 patients treated with natalizumab + TMS (5 Hertz).
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor

Study Record Dates

First Submitted

August 1, 2019

First Posted

August 20, 2019

Study Start

October 1, 2019

Primary Completion

October 1, 2021

Study Completion

October 1, 2022

Last Updated

August 21, 2019

Record last verified: 2019-08

Data Sharing

IPD Sharing
Will share

To publish the protocol study and its results in Scientific Journals

Shared Documents
STUDY PROTOCOL, SAP, ICF, CSR
Time Frame
The protocol study may be published in the last quarter of 2019. The results could be published at the end of the study (about 2022).
Access Criteria
Throug the website of research group https://www.imibic.org/grupo/35 or after request it (by previous e-mail from one of investigators)