Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202403516079512 Date of Approval: 05/03/2024
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Treatment of Progressive Multiple Sclerosis-related Cognitive Impairment, Fatigue, and Depression Using Repetitive Transcranial Magnetic Stimulation
Official scientific title Treatment of Progressive Multiple Sclerosis-related Cognitive Impairment, Fatigue, and Depression Using Repetitive Transcranial Magnetic Stimulation
Brief summary describing the background and objectives of the trial Background: Multiple sclerosis (MS) is the most frequent central nervous system disease of early and mid-adulthood. Cognitive impairment, fatigue, and depression are prevalent in MS, however, these symptoms have been underestimated in the past. It is now recognized that these symptoms are linked to considerable disability and negatively affect patients’ quality of life. Sandyk, 1998 showed in various studies how electromagnetic stimulation manages to improve the visual and cognitive deficit associated with MS, as well as reducing the symptomatic exacerbation. Many studies were conducted on the application of conventional repetitive Transcranial Magnetic Stimulation (rTMS) to treat such disabling symptoms as cognitive impairment, depression, and fatigue. These studies potentially showed controversies due to heterogeneous MS symptomatology and heterogeneous research methodologies, which is a fundamental issue to be resolved in the future. Thus, further trials replicating the results will help establish the exact level of evidence for the use of rTMS as a supplementary treatment for MS. Objectives: The primary objective is to investigate the efficacy of high frequency rTMS on cognitive impairment, fatigue, and depression in a sample of Egyptian progressive MS patients. The secondary objective is to evaluate the effects of these protocols on the patients’ MS-related sphincteric dysfunction.
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Nervous System Diseases
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Treatment: Devices
Anticipated trial start date 01/04/2024
Actual trial start date 28/03/2024
Anticipated date of last follow up 01/04/2025
Actual Last follow-up date
Anticipated target sample size (number of participants) 60
Actual target sample size (number of participants)
Recruitment status Recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Crossover: all participants receive all interventions in different sequence during study Randomised Simple randomization using a randomization table created by a computer software program Allocation was determined by the holder of the sequence who is situated off site Masking/blinding used Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Real repetitive Transcranial Magnetic Stimulation of DLPFC 6 sessions: Each session lasts for 580 seconds and consists of 1000 pulses with a frequency of 10 Hz, at 90% of resting motor threshold for DLPFC stimulation. 6 every-other-day sessions (over 2 weeks) Resting motor threshold is first determined in the abductor pollicis brevis according to the method described by Rossini et al., 1994. Each session lasts for 580 seconds and consists of 1000 pulses with a frequency of 10 Hz, at 90% of resting motor threshold for DLPFC stimulation, in 25 trains, 40 pulses per train with 20 seconds inter-train interval. The coil is held in the optimal scalp position with the handle pointing backwards at 45° of the sagittal plane to ensure that the induced electric field be perpendicular to the underlying gyrus. The site of stimulation of left DLPFC corresponds to F3 of 10-20 system of EEG. MagVenture MagPro X100 repetitive transcranial magnetic stimulator (Farum, Denmark) with Magoption and a 75-mm figure-of-eight coil (MagVenture cool B65) will be used. 20
Experimental Group Real repetitive Transcranial Magnetic Stimulation over pre SMA 6 sessions: Each session lasts for 580 seconds and consists of 1000 pulses with a frequency of 10 Hz, at 110% of resting motor threshold for pre SMA stimulation. 6 every-other-day sessions (over 2 weeks) Resting motor threshold is first determined in the abductor pollicis brevis according to the method described by Rossini et al., 1994. Each session lasts for 580 seconds and consists of 1000 pulses with a frequency of 10 Hz, at 110% of resting motor threshold for pre SMA stimulation, in 25 trains, 40 pulses per train with 20 seconds inter-train interval. The coil is held in the optimal scalp position to ensure that the induced electric field be perpendicular to the underlying gyrus. The site of stimulation for pre-SMA corresponds to 2 cm anterior to Cz. MagVenture MagPro X100 repetitive transcranial magnetic stimulator (Farum, Denmark) with Magoption and a 75-mm figure-of-eight coil (MagVenture cool B65) will be used. 20
Control Group Sham repetitive Transcranial Magnetic Stimulation of DLPFC Similar pattern of stimulation of the experimental group which will receive intervention at DLPFC but using an inactive coil that is shielded yet optically identical to the active coil. 6 every-other-day sessions (over 2 weeks) Similar pattern of stimulation of the experimental group which will receive intervention at DLPFC but using an inactive coil that is shielded yet optically identical to the active coil. It produces sounds and sensations similar to the active coil but does not produce therapeutic effects. Later on, patients in this group will cross over to receive real rTMS over as proposed. 10 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
-Definite MS patients according to 2017 revisions of the McDonald criteria. -Progressive types of MS: Patient must fulfill diagnostic criteria of either: Secondary progressive MS (SPMS) or Primary progressive MS (PPMS) -Free of clinical relapses for at least 3 months prior to inclusion. -Free of steroid treatment for at least 6 weeks prior to inclusion. -No change in their medications, whether disease modifying treatment or symptomatic therapy for at least 3 months if applicable. -EDSS score ≤ 6 points and stable over the past 3 months. -A score of <34 on Symbol Digit Modalities Test, a score of ≥ 12 on the Beck Depression Inventory (Beck et al., 1961), a score of ≥ 38 on the Modified Fatigue Impact Scale. -Level of education: at least can read and write. -Written informed consent from the participants -Conditions that could affect the participants’ level of cognition, fatigue, or depression, including; pregnancy, history of substance use disorder, history of significant neurological disorder other than MS, psychiatric, endocrinological, hepatic, renal, collagen, or other systemic comorbidities that could affect these symptoms. -Contraindication to TMS: history of seizures, skull bone defects, metal fragments in the head, implanted metallic devices such as cardiac pacemakers, cochlear implants, medical pumps…, etc. -Illiterate patients. Adult: 19 Year-44 Year,Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 65 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 12/02/2024 The Research Ethics Committee at the Faculty of Medicine Ain Shams University
Ethics Committee Address
Street address City Postal code Country
38 Abbassia Square Cairo 11591 Egypt
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome To investigate the efficacy of high frequency rTMS on cognitive impairment using Symbol Digit Modalities Test, fatigue using Arabic version of Modified Fatigue Impact Scale, and depression using Arabic version of Beck Depression inventory in a sample of Egyptian progressive MS patients. Immediately after the last stimulation session, 4 weeks and at 12 weeks after the end of the intervention.
Secondary Outcome To evaluate the effects of high frequency rTMS on the patients’ MS-related sphincteric dysfunction using the Arabic International Consultation on Incontinence Questionnaire-Short Form Scale, and on the patients’ walking performance using Timed 25-Foot walk test and Functional Ambulation Category. Immediately after the last stimulation session, at 4 weeks and at 12 weeks after the end of the intervention.
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Multiple Sclerosis unit Neurology Department Ain Shams University 38 Abbassia Square Cairo 11591 Egypt
FUNDING SOURCES
Name of source Street address City Postal code Country
Science Technology and Innovation Funding Authority 101 Kasr Al-Ainy Cairo Egypt
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Science Technology and Innovation Funding Authority 101 Kasr Al-Ainy Cairo 11694 Egypt Funding Agency
Secondary Sponsor Neurology department Ain Shams University 38 Abbassia Square Cairo 11591 Egypt University
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Nevine El Nahas nevine_elnahas@med.asu.edu.eg +201227910517 38 Abbassia square
City Postal code Country Position/Affiliation
Cairo 11591 Egypt Professor of Neurology Ain Shams University
Role Name Email Phone Street address
Public Enquiries Azza Abdelnasser azza.abdelnasser@med.asu.edu.eg +201001240246 38 Abbassia square
City Postal code Country Position/Affiliation
Cairo 11591 Egypt Professor of Neurology Ain Shams University
Role Name Email Phone Street address
Scientific Enquiries Maha Sabry sabrymaha1@med.asu.edu.eg +201092998698 38 Abbassia square
City Postal code Country Position/Affiliation
Cairo 11591 Egypt Assistant Lecturer of Neurology Ain Shams University
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes All of the individual participant data collected during the trial, after deidentification. Analytic Code,Clinical Study Report,Informed Consent Form,Statistical Analysis Plan,Study Protocol Immediately following publication, ending 6 months following article publication. Open access, For individual participant metanalysis, Data will be made available on scientifically-sound basis, Data requesting should be directed to the principal investigator via E-mail
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information