Clinical trial NCT03892863: Repetitive Transcranial Magnetic Stimulation as Therapy for Depression in Amyotrophic Lateral Sclerosis
Official title: A Pilot Study of Repetitive Transcranial Magnetic Stimulation for Improvement of Depression in Amyotrophic Lateral Sclerosis
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Amyotrophic Lateral Sclerosis
Keywords: Amyotrophic Lateral Sclerosis
depression
rTMS
Lead sponsor: Jagiellonian University
Sponsor class: OTHER
First posted: 2019-03-27
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients will be randomly assigned to real or placebo (sham) stimulation.
Primary purpose: TREATMENT

Brief summary: 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. Depression is a frequent complication of ALS, which further decreases quality of life and the available data concerning effectivity of antidepressant drugs are conflicting. Repetitive Transcranial Magnetic Stimulation (rTMS) is a noninvasive method of modulation of brain plasticity with confirmed antidepressive effect. The purpose of this study is to compare the effectiveness of rTMS in improving the depression in patients with ALS with placebo stimulation. Intervention will include 10 daily sessions. In each session 3000 magnetic pulses will be administered over the left dorsolateral prefrontal cortex. Assessment depression severity will be made before and after therapy, as well as two and four weeks later.

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. Depression is a frequent complication of ALS, which further decreases quality of life and the available data concerning effectivity of antidepressant drugs are conflicting. Similarly, the apathy may also complicate ALS and worsen the prognosis. Repetitive Transcranial Magnetic Stimulation (rTMS) is a noninvasive method of modulation of brain plasticity with proved antidepressive effect in patients suffering from major depression and in depression associated with several neurological disorders such as Parkinson's disease or stroke.

The purpose of this study is to compare the effectiveness rTMS in improving the depression and - as a secondary outcome - the apathy and daily functioning 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 depression severity and of apathy and daily functioning will be made before and after therapy, as well as two and four weeks later.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of definite or probable ALS according to el Escorial criteria (Brooks et al. 2000)
* Depression defined as the score in Beck's Depression Inventory ≥14
* 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

Primary outcomes:
measure: Beck's Depression Inventory ater rTMS, total score, range 0 to 63, with higher values representing a worse outcome
timeFrame: Before rTMS, directly (on the same day) after finishing rTMS
measure: Beck's Depression Inventory first follow up, total score, range 0 to 63, with higher values representing a worse outcome
timeFrame: Before rTMS, two weeks after finishing rTMS
measure: Beck's Depression Inventory second follow up, total score, range 0 to 63, with higher values representing a worse outcome
timeFrame: Before rTMS, four weeks after finishing rTMS
Secondary outcomes:
measure: Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised after rTMS, total score, range 0 to 40 with higher values representing a better outcome
timeFrame: Before rTMS, directly (on the same day) after finishing rTMS
measure: Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised first follow up, total score, range 0 to 40 with higher values representing a better outcome
timeFrame: Before rTMS, two weeks after finishing rTMS
measure: Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised second follow up, total score, range 0 to 40 with higher values representing a better outcome
timeFrame: Before rTMS, four weeks after finishing rTMS
measure: Apathy Evaluation Scale Clinical Version ater rTMS, total score, range 18 to 72 with higher values representing a worse outcome
timeFrame: Before rTMS, directly (on the same day) after finishing rTMS
measure: Apathy Evaluation Scale Clinical Version first follow up, total score, range 18 to 72 with higher values representing a worse outcome
timeFrame: Before rTMS, two weeks after finishing rTMS
measure: AES-C second follow up, total score, range 18 to 72 with higher values representing a worse outcome
timeFrame: Before rTMS, four weeks after finishing rTMS
Other outcomes:
Locations:
city: Kraków
country: Poland
facility: Jagiellonian University Medical College, Department of Neurology
Study officials:
affiliation: Department of Neurology, Jagiellonian University Medical College
name: Jakub M Antczak, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Brooks BR, Miller RG, Swash M, Munsat TL; World Federation of Neurology Research Group on Motor Neuron Diseases. El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord. 2000 Dec;1(5):293-9. doi: 10.1080/146608200300079536. No abstract available.
citation: Fregni F, Santos CM, Myczkowski ML, Rigolino R, Gallucci-Neto J, Barbosa ER, Valente KD, Pascual-Leone A, Marcolin MA. Repetitive transcranial magnetic stimulation is as effective as fluoxetine in the treatment of depression in patients with Parkinson's disease. J Neurol Neurosurg Psychiatry. 2004 Aug;75(8):1171-4. doi: 10.1136/jnnp.2003.027060.
citation: Lefaucheur JP, Andre-Obadia N, Antal A, Ayache SS, Baeken C, Benninger DH, Cantello RM, Cincotta M, de Carvalho M, De Ridder D, Devanne H, Di Lazzaro V, Filipovic SR, Hummel FC, Jaaskelainen SK, Kimiskidis VK, Koch G, Langguth B, Nyffeler T, Oliviero A, Padberg F, Poulet E, Rossi S, Rossini PM, Rothwell JC, Schonfeldt-Lecuona C, Siebner HR, Slotema CW, Stagg CJ, Valls-Sole J, Ziemann U, Paulus W, Garcia-Larrea L. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS). Clin Neurophysiol. 2014 Nov;125(11):2150-2206. doi: 10.1016/j.clinph.2014.05.021. Epub 2014 Jun 5.
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.
citation: Shen X, Liu M, Cheng Y, Jia C, Pan X, Gou Q, Liu X, Cao H, Zhang L. Repetitive transcranial magnetic stimulation for the treatment of post-stroke depression: A systematic review and meta-analysis of randomized controlled clinical trials. J Affect Disord. 2017 Mar 15;211:65-74. doi: 10.1016/j.jad.2016.12.058. Epub 2017 Jan 10.