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

Sponsor

Jagiellonian University (Other)

Overall Status

Withdrawn

CT.gov ID

NCT03892382

Collaborator

(none)

Enrollment

Location

Arms

25.5

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Condition or Disease	Intervention/Treatment	Phase
Amyotrophic Lateral Sclerosis	Device: rTMS	N/A

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 Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Patients will be randomly assigned to real or placebo (sham) stimulation.Patients will be randomly assigned to real or placebo (sham) stimulation.

Masking:

Triple (Participant, Investigator, Outcomes 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.

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Nov 15, 2019

Anticipated Primary Completion Date :

Jun 30, 2021

Anticipated Study Completion Date :

Dec 31, 2021

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Apathy Evaluation Scale Clinical Version after rTMS, total score, range 18 to 72 with higher values representing a worse outcome [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.
Apathy Evaluation Scale Clinical Version first follow up, total score, range 18 to 72 with higher values representing a worse outcome [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.
Apathy Evaluation Scale Clinical Version second follow up, total score, range 18 to 72 with higher values representing a worse outcome [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

Secondary Outcome Measures

Lateral Sclerosis Functional Rating Scale-Revised after rTMS, total score, range 0 to 40 with higher values representing a better outcome [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.
Lateral Sclerosis Functional Rating Scale-Revised first follow up, total score, range 0 to 40 with higher values representing a better outcome [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.
Lateral Sclerosis Functional Rating Scale-Revised second follow up, total score, range 0 to 40 with higher values representing a better outcome [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
Beck's Depression Inventory ater rTMS, total score, range 0 to 63, with higher values representing a worse outcome [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.
Beck's Depression Inventory first follow up, total score, range 0 to 63, with higher values representing a worse outcome [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.
Beck's Depression Inventory second follow up, total score, range 0 to 63, with higher values representing a worse outcome [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Diagnosis of definite or probable ALS according to el Escorial criteria (Brooks et al.

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