Clinical trial NCT03627416: Repetitive Transcranial Magnetic Stimulation as Therapy in Hereditary Spastic Paraplegia and Adrenomyeloneuropathy
Official title: A Pilot Study of Repetitive Transcranial Magnetic Stimulation for Improvement of Gait in Hereditary Spastic Paraplegia and Adrenomyeloneuropathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hereditary Spastic Paraplegia
Adrenomyeloneuropathy
Keywords: Hereditary spastic paraplegia
repetitive transcranial magnetic stimulation
disturbed gait
Adrenomyeloneuropthy
Lead sponsor: Jagiellonian University
Sponsor class: OTHER
First posted: 2018-08-13
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 16 patients with HSP or AMN will receive either active and sham stimulation in random order
Primary purpose: TREATMENT

Brief summary: Hereditary spastic paraplegia (HSP) is the group of inherited disorders, characterized by progressive gait disturbance. There is no established therapy. Adrenoleukodystrophy (AMN) is an x-linked hereditary disease. One of its form, the adrenomyeloneuropathy has the same symptoms as HSP. Current therapeutic options for AMN are very limited. Repetitive Transcranial Magnetic Stimulation (rTMS) is a noninvasive method of modulation of brain plasticity. The purpose of this study is to compare the effectiveness of rTMS in improving the HSP- and AMN-related gait disturbance and other symptoms with sham stimulation.

Intervention will include five daily sessions. In each session 1500 magnetic pulses will be administered to each of both primary motor areas for lower extremities. Assessment of gait and of strength and spasticity of lower extremities will be made before and after therapy, as well as two weeks later.

Detailed description: Hereditary spastic paraplegia (HSP) is a group of inherited disorders, characterized by progressive gait disturbance with weakness and spasticity, which predominate in lower extremities. There is no established therapy. Adrenoleukodystrophy (AMN) is an x-linked hereditary disease. One of its form, the adrenomyeloneuropathy has the same symptoms as HSP. Current therapeutic options for AMN are very limited. Repetitive Transcranial Magnetic Stimulation (rTMS), a noninvasive method of modulation of brain plasticity proved to be effective in improving the gait performance in several conditions such as Parkinson Disease, vascular Parkinsonism, partial spinal cord injury and in post-stroke paresis. Previous studies documented also altered cortical excitability in HSP patients.

The purpose of this study is 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.

Intervention will include five daily sessions. In each session 1500 magnetic pulses will be administered to each of both primary motor areas for lower extremities. Assessment of gait and of strength and spasticity of lower extremities will be made before and after therapy, as well as two weeks later.

Eligibility criteria: Inclusion Criteria:

* diagnosis of hereditary spastic paraplegia - confirmed genetically, on the basis of family history or on exclusion or diagnosis of adrenomyeloneuropathy - 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 ethiology 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

Primary outcomes:
measure: Change From Baseline Walking Time in 10 Meter Walk Test to the Measurement Taken Directly After rTMS
timeFrame: Before rTMS, directly (on the same day) after rTMS
Secondary outcomes:
measure: Change in Timed up and go Test
timeFrame: Baseline, directly (on the same day) after rTMS and 14 days later
measure: Change in Medical Research Council Scale (MRC)
timeFrame: Baseline, directly (on the same day) after rTMS and 14 days later
measure: Modified Ashworth Scale
timeFrame: Baseline, directly (on the same day) after rTMS and 14 days later
measure: Change From Baseline Walking Time in 10 Meter Walk Test to the Measurement Taken Two Weeks After rTMS
timeFrame: Baseline, 14 days after rTMS
Other outcomes:
Locations:
city: Kraków
country: Poland
facility: Jagiellonian University Medical College, Department of Neurology
Study officials:
affiliation: Jagiellonian University Medical College, Department of Neurology
name: Jakub M Antczak, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rossi S, Hallett M, Rossini PM, Pascual-Leone A; Safety of TMS Consensus Group. Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol. 2009 Dec;120(12):2008-2039. doi: 10.1016/j.clinph.2009.08.016. Epub 2009 Oct 14.
citation: Antczak J, Pera J, Dabros M, Kozminski W, Czyzycki M, Wezyk K, Dwojak M, Banach M, Slowik A. The Effect of Repetitive Transcranial Magnetic Stimulation on Motor Symptoms in Hereditary Spastic Paraplegia. Neural Plast. 2019 May 12;2019:7638675. doi: 10.1155/2019/7638675. eCollection 2019.