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

August 30, 2021 updated by: Jakub Antczak

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

15

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Poland
      • Kraków, Poland, 31503
        • Jagiellonian University Medical College, Department of Neurology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 78 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Sham Comparator: Sham rTMS
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.
Device: rTMS
high frequency rTMS to induce the long term potentiation of primary motor areas for the muscles of lower extremities
Experimental: active rTMS
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.
Device: rTMS
high frequency rTMS to induce the long term potentiation of primary motor areas for the muscles of lower extremities

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline Walking Time in 10 Meter Walk Test to the Measurement Taken Directly After rTMS
Time Frame: 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.
Before rTMS, directly (on the same day) after rTMS

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Timed up and go Test
Time Frame: 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.
Baseline, directly (on the same day) after rTMS and 14 days later
Change in Medical Research Council Scale (MRC)
Time Frame: 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.
Baseline, directly (on the same day) after rTMS and 14 days later
Modified Ashworth Scale
Time Frame: 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.
Baseline, directly (on the same day) after rTMS and 14 days later
Change From Baseline Walking Time in 10 Meter Walk Test to the Measurement Taken Two Weeks After rTMS
Time Frame: 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.
Baseline, 14 days after rTMS

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Jakub Antczak

Investigators

  • Principal Investigator: Jakub M Antczak, MD, Jagiellonian University Medical College, Department of Neurology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 9, 2017

Primary Completion (Actual)

January 1, 2019

Study Completion (Actual)

January 1, 2019

Study Registration Dates

First Submitted

October 23, 2017

First Submitted That Met QC Criteria

August 8, 2018

First Posted (Actual)

August 13, 2018

Study Record Updates

Last Update Posted (Actual)

September 27, 2021

Last Update Submitted That Met QC Criteria

August 30, 2021

Last Verified

August 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • JagiellonianU59

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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