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

Hereditary Spastic Paraplegia Clinical Trial

Official title:

A Pilot Study of Repetitive Transcranial Magnetic Stimulation for Improvement of Gait in Hereditary Spastic Paraplegia and Adrenomyeloneuropathy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03627416
• Other study ID #: JagiellonianU59
• Status: Completed
• Phase: N/A
• Start date: January 9, 2017
• Est. completion date: January 1, 2019

Study information

• Verified date: August 2021
• Source: Jagiellonian University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: January 1, 2019
• Est. primary completion date: January 1, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Adrenoleukodystrophy
• Adrenomyeloneuropathy
• Hereditary Spastic Paraplegia
• Muscle Spasticity
• Paraplegia
• Spastic Paraplegia, Hereditary

Intervention

Device:
• rTMS
high frequency rTMS to induce the long term potentiation of primary motor areas for the muscles of lower extremities

Locations

Country	Name	City	State
Poland	Jagiellonian University Medical College, Department of Neurology	Kraków

Sponsors (1)

Lead Sponsor	Collaborator
Jakub Antczak

Country where clinical trial is conducted

Poland, 

References & Publications (1)

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( — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline Walking Time in 10 Meter Walk Test to the Measurement Taken Directly After rTMS	Change in time of walking barefoot the distance of 10 meters with maximal speed, but safely, between baseline and directly after rTMS.	Before rTMS, directly (on the same day) after rTMS
Secondary	Change in Timed up and go Test	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.	Baseline, directly (on the same day) after rTMS and 14 days later
Secondary	Change in Medical Research Council Scale (MRC)	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.	Baseline, directly (on the same day) after rTMS and 14 days later
Secondary	Modified Ashworth Scale	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.	Baseline, directly (on the same day) after rTMS and 14 days later
Secondary	Change From Baseline Walking Time in 10 Meter Walk Test to the Measurement Taken Two Weeks 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.	Baseline, 14 days after rTMS