- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00833820
Repetitive Transcranial Magnetic Stimulation (rTMS) in Amyotrophic Lateral Sclerosis (rTMS-ALS)
Repetitive Transcranial Magnetic Stimulation in Amyotrophic Lateral Sclerosis
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Eligible patients should have a diagnosis of definite ALS according to the El Escorial revised criteria with clear clinical upper and lower motor neuron signs. Twenty patients with definite ALS will be enrolled and will be allocated to the treatment: 10 active and 10 sham stimulation. Patients will be randomly allocated by one of the investigators not involved in follow-up evaluations and data analysis. Stratified block randomisation will be performed such that the two treatment groups will be evenly balanced for disease severity, as evaluated with the revised ALS functional rating scale (ALSFRS-R), and duration. The patients and the neurologists assessing the outcomes will be blinded to group assignment.
Outcome measures Patients will be evaluated at the beginning of the treatment and every month until the end of the study at 1 year. At each visit, patients will be evaluated using the ALSFRS-R and manual muscle testing (MMT). MMT testing will be performed by means of the Medical Research Council (MRC) Scale. To obtain an estimate of the overall limb muscle strength we will calculate a MRC compound score by adding the MRC scores of eight upper limb muscles and five lower limb muscles for each side and dividing the sum by the number of muscles tested (26 muscles). We will test the following muscles: biceps brachii, deltoid, triceps brachii, extensor carpi radialis , extensor digitorum communis, abductor digiti minimi, abductor pollicis brevis, opponens pollicis, iliopsoas, rectus femoris, tibialis anterior, extensor hallucis longus, gastrocnemius.
The primary outcome measure will be the rate of decline of ALSFRS-R scores. Secondary outcome measure will be the rate of decline in MMT.
Transcranial brain stimulation Central motor conduction time for the first dorsal interosseous muscle will calculated by subtracting the peripheral conduction time, from spinal cord to muscles, from the latency of responses evoked by cortical stimulation at the maximum stimulator output during voluntary contraction at about 20% of maximum.
Repetitive TMS will be applied over the hand motor area using a MagPro (Medtronic A/S Denmark) stimulator and a figure of eight-shaped coil.
Active rTMS will be performed using the cTBS pattern in which 3 pulses of stimulation are given at 50Hz, repeated every 200 ms for a total of 600 pulses. We will use a butterfly coil (MCF-B-65) with the handle pointed posteriorly and approximately perpendicular to the central sulcus. The initial direction of the current induced in the brain will be posterior-anterior. The stimulation intensity will be 80 % of the active motor threshold (AMT), defined as the minimum single pulse intensity required to produce a motor evoked potential greater than 200 uV on more than five out of ten trials from the contracted contralateral first interosseous muscle. This protocol leads to pronounced and prolonged suppression of cortical excitability that reaches a maximum about 5-10 min after the end of the stimulation.
Sham rTMS will be performed using the same stimulator connected to the placebo butterfly coil MCF-P-B-65 which has no stimulating effect on the cortex but produces similar auditory and tactile sensations as the active coil. The site of stimulation and the number of stimuli will be identical to those used for the active magnetic rTMS.
Repetitive TMS will be performed bilaterally. The order of stimulation of the two hemispheres will be randomized. The stimulation of the two hemispheres will be performed sequentially at an interval of one minute. The motor cortex of each side will be stimulated for five consecutive days every month for twelve consecutive months. In the patients with absent first dorsal interosseous motor evoked potentials after stimulation of one hemisphere, the repetitive stimulation will be performed at the same intensity used for the opposite hemisphere.
Statistical analysis Statistical analysis will be performed using a two-factor (TIME and TREATMENT) repeated measures analysis of variance.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 3
Contacts and Locations
Study Locations
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-
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Rome, Italy, 00168
- Institute of neurology Università Cattolica
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Eligible patients should have a diagnosis of definite ALS according to the El Escorial revised criteria with clear clinical upper and lower motor neuron signs.
Exclusion Criteria:
Contraindications to transcranial magnetic stimulation:
- Tracheostomy
- Pace-maker
- Implanted metallic devices
- Epilepsy
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: A
Patients receiving real rTMS
|
Repetitive transcranial magnetic stimulation will be performed using a focal coil held over motor cortex on each hemisphere.
Stimulation protocol used will be the cTBS in which three pulses of stimulation are given at 50 Hz, repeated every 200 ms for a total of 300 pulses delivered over the right motor cortex.
The stimulus intensity will be set at 80% of Action Motor Threshold.
|
Sham Comparator: B
patients receiving sham stimulation
|
Sham repetitive transcranial magnetic stimulation will be performed using the same stimulator connected to the placebo butterfly coil MCF-P-B-65 which has no stimulating effect on the cortex but produces similar auditory and tactile sensations as the active coil.
The site of stimulation and the number of stimuli will be identical to those used for the active magnetic rTMS.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Rate of decline of ALSFRS-R score
Time Frame: one year
|
one year
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Rate of decline of manual muscle force testing score
Time Frame: one year
|
one year
|
Collaborators and Investigators
Investigators
- Principal Investigator: Vincenzo Di Lazzaro, MD, Institute of Neurology Università Cattolica Roma
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 001 (NavyGHB)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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