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

Primary Purpose

Hereditary Spastic Paraplegia, Adrenomyeloneuropathy

Status
Completed
Phase
Not Applicable
Locations
Poland
Study Type
Interventional
Intervention
rTMS
Sponsored by
Jakub Antczak
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hereditary Spastic Paraplegia focused on measuring Hereditary spastic paraplegia, repetitive transcranial magnetic stimulation, disturbed gait, Adrenomyeloneuropthy

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Jagiellonian University Medical College, Department of Neurology

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

active rTMS

Sham rTMS

Arm Description

10 hertz (Hz) rTMS will be administered over bilateral primary motor areas for the muscles of lower extremities. Therapy will include five daily sessions (on consecutive week days). In every sessions 3000 magnetic pulses of 90% of the resting motor threshold intensity will be elicited.

Sham stimulation will mimic the active one except that the stimulating coil will be held perpendicularly to the scalp, which assures similar impression as the active stimulation but prevents that significant magnetic field will reach brain tissue.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.

Full Information

First Posted
October 23, 2017
Last Updated
August 30, 2021
Sponsor
Jakub Antczak
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1. Study Identification

Unique Protocol Identification Number
NCT03627416
Brief Title
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

2. Study Status

Record Verification Date
August 2021
Overall Recruitment Status
Completed
Study Start Date
January 9, 2017 (Actual)
Primary Completion Date
January 1, 2019 (Actual)
Study Completion Date
January 1, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Jakub Antczak

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hereditary Spastic Paraplegia, Adrenomyeloneuropathy
Keywords
Hereditary spastic paraplegia, repetitive transcranial magnetic stimulation, disturbed gait, Adrenomyeloneuropthy

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Model Description
16 patients with HSP or AMN will receive either active and sham stimulation in random order
Masking
ParticipantOutcomes Assessor
Masking Description
Sham stimulation will be provided by holding the stimulating coil perpendicularly to the scalp, which assures similar impression as during active stimulation but prevents significant magnetic field to reach the brain tissue.
Allocation
Randomized
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
active rTMS
Arm Type
Experimental
Arm Description
10 hertz (Hz) rTMS will be administered over bilateral primary motor areas for the muscles of lower extremities. Therapy will include five daily sessions (on consecutive week days). In every sessions 3000 magnetic pulses of 90% of the resting motor threshold intensity will be elicited.
Arm Title
Sham rTMS
Arm Type
Sham Comparator
Arm Description
Sham stimulation will mimic the active one except that the stimulating coil will be held perpendicularly to the scalp, which assures similar impression as the active stimulation but prevents that significant magnetic field will reach brain tissue.
Intervention Type
Device
Intervention Name(s)
rTMS
Intervention Description
high frequency rTMS to induce the long term potentiation of primary motor areas for the muscles of lower extremities
Primary Outcome Measure Information:
Title
Change From Baseline Walking Time in 10 Meter Walk Test to the Measurement Taken Directly After rTMS
Description
Change in time of walking barefoot the distance of 10 meters with maximal speed, but safely, between baseline and directly after rTMS.
Time Frame
Before rTMS, directly (on the same day) after rTMS
Secondary Outcome Measure Information:
Title
Change in Timed up and go Test
Description
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.
Time Frame
Baseline, directly (on the same day) after rTMS and 14 days later
Title
Change in Medical Research Council Scale (MRC)
Description
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.
Time Frame
Baseline, directly (on the same day) after rTMS and 14 days later
Title
Modified Ashworth Scale
Description
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.
Time Frame
Baseline, directly (on the same day) after rTMS and 14 days later
Title
Change From Baseline Walking Time in 10 Meter Walk Test to the Measurement Taken Two Weeks After rTMS
Description
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.
Time Frame
Baseline, 14 days after rTMS

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jakub M Antczak, MD
Organizational Affiliation
Jagiellonian University Medical College, Department of Neurology
Official's Role
Principal Investigator
Facility Information:
Facility Name
Jagiellonian University Medical College, Department of Neurology
City
Kraków
ZIP/Postal Code
31503
Country
Poland

12. IPD Sharing Statement

Citations:
PubMed Identifier
19833552
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.
Results Reference
result
PubMed Identifier
31214256
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.
Results Reference
derived

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

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