Repetitive Transcranial Magnetic Stimulation as Therapy in Hereditary Spastic Paraplegia and Adrenomyeloneuropathy

Not Applicable

Completed

• Conditions: Hereditary Spastic Paraplegia; Adrenomyeloneuropathy

• Registration Number: NCT03627416
• Lead Sponsor: Jakub Antczak

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.

Study Timeline

• Study Start: 2017-01-09
• Study First Submitted: 2017-10-23
• Study First Submitted QC: 2018-08-08
• Study First Posted: 2018-08-13
• Primary Completion: 2019-01-01
• Study Completion: 2019-01-01
• Results First Submitted: 2021-02-09
• Status Verified: 2021-08
• Results First Submitted QC: 2021-08-30
• Last Update Submitted: 2021-08-30
• Results First Posted: 2021-09-27
• Last Update Posted: 2021-09-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 15

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Primary Outcome Measures

Name	Time	Method
Change From Baseline Walking Time in 10 Meter Walk Test to the Measurement Taken Directly After rTMS	Before rTMS, directly (on the same day) after rTMS	Change in time of walking barefoot the distance of 10 meters with maximal speed, but safely, between baseline and directly after rTMS.

Secondary Outcome Measures

Name	Time	Method
Change in Timed up and go Test	Baseline, directly (on the same day) after rTMS and 14 days later	Time of standing up from a chair, walking three metres to cross a line drawn 3 meters ahead and going back to sit down on the chair.
Change in Medical Research Council Scale (MRC)	Baseline, directly (on the same day) after rTMS and 14 days later	Change in bilateral assessment of the strength of following movements: hip flexion, knee flexion and extension, ankle flexion and extension. Assessment will be made according to six degrees (0 to 5) MRC scale, with higher values representing stronger movements, which is better outcome. Values are averaged from all movements tested.
Modified Ashworth Scale	Baseline, directly (on the same day) after rTMS and 14 days later	Bilateral assessment of spasticity in following movements: hip flexion, knee flexion and extension, ankle flexion and extension. Assessment will be made according to six degrees (0 to 5) Modified Ashworth Scale, with higher values representing more severe spasticity, which is worse outcome. Values are averaged from all movements tested.
Change From Baseline Walking Time in 10 Meter Walk Test to the Measurement Taken Two Weeks After rTMS	Baseline, 14 days after rTMS	Change in time of walking barefoot the distance of 10 meters with maximal speed, but safely, between baseline and 14 days after finishing rTMS therapy.

Trial Locations

Locations (1)

Jagiellonian University Medical College, Department of Neurology; 🇵🇱 Kraków, Poland