Repetitive Transcranial Magnetic Stimulation as Therapy for Apathy in Amyotrophic Lateral Sclerosis

February 6, 2020 updated by: Jakub Antczak, Jagiellonian University

A Pilot Study of Repetitive Transcranial Magnetic Stimulation for Improvement of Apathy in Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive loss of central and peripheral motor neurons. ALS leads to death usually within 3 to 5 years from the onset of the symptoms. Available treatment can prolong the disease duration but cannot modify the disease course. Apathy is a frequent complication of ALS, affecting up to 30% of patients and affecting negatively the survival. Repetitive Transcranial Magnetic Stimulation (rTMS) is a noninvasive method of modulation of brain plasticity with confirmed beneficial effect on apathy in several neurologic and psychiatric conditions. The purpose of this study is to compare the effectiveness of rTMS in improving the apathy in patients with ALS with placebo stimulation.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive loss of central and peripheral motor neurons. ALS leads to death usually within 3 to 5 years from the onset of the symptoms. Available treatment can prolong the disease duration but cannot modify the disease course. Apathy is a frequent complication of ALS, which negatively influences quality of life (caga et al. 2018) and is an independent poor prognostic factor for survival (Caga et al. 2016). Similarly, the depression is also a frequent complication of ALS. Repetitive Transcranial Magnetic Stimulation (rTMS) is a noninvasive method of modulation of brain plasticity with confirmed beneficial effect on apathy in several neurologic and psychiatric conditions like mild cognitive impairment (Padala et al. 2018), stroke (Sasaki et al. 2017), Alzheimer disease (Nguyen et al. 2017) and schizophrenia (Prikryl et al. 2013). The purpose of this study is to compare the effectiveness of rTMS in improving the apathy in patients with ALS with placebo stimulation and - as a secondary outcome - depression in patients with ALS.

Intervention will include ten daily sessions of rTMS. In each session 3000 magnetic pulses will be administered over the left dorsolateral prefrontal cortex. Stimulation intensity will equal 120% of the motor threshold value for the right first dorsal interosseus.

Assessment of apathy and of depression and daily functioning will be made before and after therapy, as well as two and four weeks later.

Study Type

Interventional

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

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Diagnosis of definite or probable ALS according to el Escorial criteria (Brooks et al. 2000)
  • Moderate or severe depression defined as the score in Beck's Depression Inventory ≥20
  • Mini-Mental State Examination score ≥26

Exclusion Criteria:

  • Psychiatric symptoms, which may negatively influence patient's tolerance and adherence to therapy
  • Respiratory insufficiency and other complications od advanced stages of ALS, which may compromise patient's ability to undergo the study procedure
  • Contraindications for rTMS as listed by the Guidelines of the International Federation of Clinical Neurophysiology (Rossi et al. 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: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Active rTMS
10 hertz (Hz) rTMS will be administered over the left dorsolateral prefrontal cortex. Therapy will include 10 daily sessions (on consecutive week days). In every sessions 3000 magnetic pulses of 120% of the resting motor threshold intensity will be elicited.
Device: rTMS
High frequency rTMS to induce the long term potentiation in the left dorsolateral prefrontal cortex.
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 in the left dorsolateral prefrontal cortex.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Apathy Evaluation Scale Clinical Version after rTMS, total score, range 18 to 72 with higher values representing a worse outcome
Time Frame: Baseline rTMS, directly (on the same 1 day) after finishing rTMS
Change from baseline score in Apathy Evaluation Scale Clinical Version to the measurement taken directly after finishing rTMS.
Baseline rTMS, directly (on the same 1 day) after finishing rTMS
Apathy Evaluation Scale Clinical Version first follow up, total score, range 18 to 72 with higher values representing a worse outcome
Time Frame: Baseline rTMS, two weeks after finishing rTMS
Change from baseline score in Apathy Evaluation Scale Clinical Version to the measurement taken two weeks after finishing rTMS.
Baseline rTMS, two weeks after finishing rTMS
Apathy Evaluation Scale Clinical Version second follow up, total score, range 18 to 72 with higher values representing a worse outcome
Time Frame: Baseline rTMS, four weeks after finishing rTMS
Change from baseline score in Apathy Evaluation Scale Clinical Version to the measurement taken four weeks after finishing rTMS
Baseline rTMS, four weeks after finishing rTMS

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Lateral Sclerosis Functional Rating Scale-Revised after rTMS, total score, range 0 to 40 with higher values representing a better outcome
Time Frame: Baseline rTMS, directly (on the same 1 day) after finishing rTMS
Change from baseline score in Lateral Sclerosis Functional Rating Scale-Revised to the measurement taken directly after finishing rTMS.
Baseline rTMS, directly (on the same 1 day) after finishing rTMS
Lateral Sclerosis Functional Rating Scale-Revised first follow up, total score, range 0 to 40 with higher values representing a better outcome
Time Frame: Baseline rTMS, two weeks after finishing rTMS
Change from baseline score in the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised to the measurement taken two weeks after finishing rTMS.
Baseline rTMS, two weeks after finishing rTMS
Lateral Sclerosis Functional Rating Scale-Revised second follow up, total score, range 0 to 40 with higher values representing a better outcome
Time Frame: Baseline rTMS, four weeks after finishing rTMS
Change from baseline score in Lateral Sclerosis Functional Rating Scale-Revised to the measurement taken directly after finishing rTMS
Baseline rTMS, four weeks after finishing rTMS
Beck's Depression Inventory ater rTMS, total score, range 0 to 63, with higher values representing a worse outcome
Time Frame: Baseline rTMS, directly (on the same 1 day) after finishing rTMS
Change from baseline score in the Beck's Depression Inventory to the measurement taken directly after finishing rTMS.
Baseline rTMS, directly (on the same 1 day) after finishing rTMS
Beck's Depression Inventory first follow up, total score, range 0 to 63, with higher values representing a worse outcome
Time Frame: Baseline rTMS, two weeks after finishing rTMS
Change from baseline score in the Beck's Depression Inventory to the measurement taken two weeks after finishing rTMS.
Baseline rTMS, two weeks after finishing rTMS
Beck's Depression Inventory second follow up, total score, range 0 to 63, with higher values representing a worse outcome
Time Frame: Baseline rTMS, four weeks after finishing rTMS
Change from baseline score in the Beck's Depression Inventory to the measurement taken four weeks after finishing rTMS.
Baseline rTMS, four weeks after finishing rTMS

Collaborators and Investigators

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

Sponsor

Jagiellonian University

Investigators

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

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 (Anticipated)

November 15, 2019

Primary Completion (Anticipated)

June 30, 2021

Study Completion (Anticipated)

December 31, 2021

Study Registration Dates

First Submitted

March 26, 2019

First Submitted That Met QC Criteria

March 26, 2019

First Posted (Actual)

March 27, 2019

Study Record Updates

Last Update Posted (Actual)

February 10, 2020

Last Update Submitted That Met QC Criteria

February 6, 2020

Last Verified

February 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • JagiellonianU62

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

After completing the study, the details of neurophysiologic diagnostics including motor threshold, the age and gender as well as individual scores of Mini-Mental State Examination, AES-C, Beck's Depression Inventory and Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised will be made available to other researchers on request.

IPD Sharing Time Frame

The data will become available after the study is published.

IPD Sharing Access Criteria

On request send by e-mail: jantczak@cm-uj.krakow.pl

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)
  • Informed Consent Form (ICF)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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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