A Pilot Study of Repetitive Transcranial Magnetic Stimulation for Improvement of Gait in Hereditary Spastic Paraplegia and Adrenomyeloneuropathy
Phase: NA
Conditions: Hereditary Spastic Paraplegia, Adrenomyeloneuropathy
Sponsor: Jakub Antczak

Study protocol 
 
 
„Repetitive Transcranial Magnetic Stimulation as 
Therapy in Hereditary Spastic Paraplegia and 
Adrenomyeloneuropathy” 
 
 
NCT03627416 
 
 
 
 
 
Document date: 06.01.2017  

Study objective: to compare the effectiveness of 10 hertz (Hz) rTMS over the primary 
motor cortices in improving the gait and strength and spasticity of lower extremities 
with sham stimulation in HSP and AMN patients.  
 
Study design: prospective, randomized, controlled, single blinded clinical trial in cross-
over design  
 
Patients: 16 subjects with HSP and AMN  
Inclusion Criteria:  
• Diagnosis of HSP - confirmed genetically, on the basis of family history or on 
exclusion or diagnosis of AMN - confirmed genetically or by the elevated plasma 
very long chain fatty acid or on family history  
• Gait disturbances affecting daily activities  
• Ability to walk 10 meters without assistance or with crutches or with rollator 
walker  
Exclusion Criteria:  
• Presence of signs or symptoms indicating other than HSP or AMN etiology of gait 
disturbances  
• Contraindications for rTMS as listed by the Guidelines of the International 
Federation of Clinical Neurophysiology (IFCN 2009) i.e. seizure in the past, 
epilepsy, presence of magnetic material in the reach of magnetic field, 
pregnancy, likelihood to get pregnant, intracranial electrodes, cardiac 
pacemaker or intracardiac lines, frequent syncopes  
 
Intervention:  
Experimental:  

active rTMS 10 hertz (Hz) rTMS was administered over bilateral primary motor areas for 
the muscles of lower extremities. Therapy included five daily sessions (on consecutive 
weekdays). In every session 3000 magnetic pulses of 90% of the resting motor threshold 
intensity was elicited.  
Sham Comparator:  
Sham rTMS Sham stimulation mimicked the active one except that the stimulating coil 
was being held perpendicularly to the scalp, which assures similar impression as the 
active stimulation but prevents that significant magnetic field will reach brain tissue.  
Every included participant underwent real and sham stimulations in random order. The 
randomization list contained blocks of random size of two or four. Information about 
assignment of every patient was kept in sealed envelopes. Eight patients received the 
active treatment first.  
 
Outcome Measures  
Primary Outcome Measure(s):  
Change from baseline Walking Time in 10 Meter Walk Test to the measurement taken 
directly after rTMS  
Secondary Outcome Measure(s):  
Change in Timed up and go Test from baseline to the measurement taken directly after 
rTMS and to the measurement taken two weeks after rTMS  
Change in Medical Research Council Scale (MRC) from baseline to the measurement 
taken directly after rTMS and to the measurement taken two weeks after rTMS  
Change in Modified Ashworth Scale from baseline to the measurement taken directly 
after rTMS and to the measurement taken two weeks after rTMS  
Change from baseline Walking Time in 10 Meter Walk Test to the measurement taken 
two weeks after rTMS  
 

Statistical analysis  
The measurements of spasticity were averaged for both extremities in each movement 
tested, and then, the scores for movements of the proximal segments of lower 
extremities, i.e., hip flexion, knee extension, and knee flexion, as well as of the distal 
segments, i.e., ankle flexion and extension, were summarized. The times of performing 
10MWT and TUG, as well as the spasticity of proximal and distal segments measured 
before active rTMS, were compared with respective measurements done after active 
rTMS and during follow-up. For sham rTMS, the same comparisons were done. Owing 
to the small number of subjects and the presence of ordinal data, the nonparametric 
Wilcoxon signed rank test was used. The significance level was set to p < 0.05. Power 
analysis was conducted in G∗Power v.3.2 software [30], for large (dz = 0.8), medium (dz 
= 0.5), and small (dz = 0.2) effect sizes, assuming a sample size of 15 subjects. The power 
for the three effect sizes was 80%, 56%, and 18%, respectively. The rest of calculations 
was done with the Statistica data analysis software system, version 12.0 (StatSoft, 2008; 
Palo Alto, CA, USA). Considering our interest in all symptoms tested (gait performance, 
weakness, and spasticity), which might respond to rTMS differently, as well as our 
intention to avoid excessive type II errors, which may occur in such a limited number of 
subjects, we decided not to conduct a correction for multiple comparisons.