Clinical trial NCT03892382: Repetitive Transcranial Magnetic Stimulation as Therapy for Apathy in Amyotrophic Lateral Sclerosis
Official title: A Pilot Study of Repetitive Transcranial Magnetic Stimulation for Improvement of Apathy in Amyotrophic Lateral Sclerosis
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Amyotrophic Lateral Sclerosis
Keywords: Amyotrophic Lateral Sclerosis
rTMS
apathy
depression
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. 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Apathy Evaluation Scale Clinical Version after rTMS, total score, range 18 to 72 with higher values representing a worse outcome
timeFrame: Baseline rTMS, directly (on the same 1 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: Baseline rTMS, two weeks after finishing rTMS
measure: Apathy Evaluation Scale Clinical Version second follow up, total score, range 18 to 72 with higher values representing a worse outcome
timeFrame: Baseline rTMS, four weeks after finishing rTMS
Secondary outcomes:
measure: Lateral Sclerosis Functional Rating Scale-Revised after rTMS, total score, range 0 to 40 with higher values representing a better outcome
timeFrame: Baseline rTMS, directly (on the same 1 day) after finishing rTMS
measure: Lateral Sclerosis Functional Rating Scale-Revised first follow up, total score, range 0 to 40 with higher values representing a better outcome
timeFrame: Baseline rTMS, two weeks after finishing rTMS
measure: Lateral Sclerosis Functional Rating Scale-Revised second follow up, total score, range 0 to 40 with higher values representing a better outcome
timeFrame: Baseline rTMS, four weeks after finishing rTMS
measure: Beck's Depression Inventory ater rTMS, total score, range 0 to 63, with higher values representing a worse outcome
timeFrame: Baseline rTMS, directly (on the same 1 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: Baseline 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: Baseline 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: Caga J, Hsieh S, Highton-Williamson E, Zoing MC, Ramsey E, Devenney E, Ahmed RM, Kiernan MC. Apathy and its impact on patient outcome in amyotrophic lateral sclerosis. J Neurol. 2018 Jan;265(1):187-193. doi: 10.1007/s00415-017-8688-4. Epub 2017 Nov 30.
citation: Caga J, Turner MR, Hsieh S, Ahmed RM, Devenney E, Ramsey E, Zoing MC, Mioshi E, Kiernan MC. Apathy is associated with poor prognosis in amyotrophic lateral sclerosis. Eur J Neurol. 2016 May;23(5):891-7. doi: 10.1111/ene.12959. Epub 2016 Jan 29.
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: Nguyen JP, Suarez A, Kemoun G, Meignier M, Le Saout E, Damier P, Nizard J, Lefaucheur JP. Repetitive transcranial magnetic stimulation combined with cognitive training for the treatment of Alzheimer's disease. Neurophysiol Clin. 2017 Feb;47(1):47-53. doi: 10.1016/j.neucli.2017.01.001. Epub 2017 Feb 1.
citation: Padala PR, Padala KP, Lensing SY, Jackson AN, Hunter CR, Parkes CM, Dennis RA, Bopp MM, Caceda R, Mennemeier MS, Roberson PK, Sullivan DH. Repetitive transcranial magnetic stimulation for apathy in mild cognitive impairment: A double-blind, randomized, sham-controlled, cross-over pilot study. Psychiatry Res. 2018 Mar;261:312-318. doi: 10.1016/j.psychres.2017.12.063. Epub 2018 Jan 5.
citation: Prikryl R, Ustohal L, Prikrylova Kucerova H, Kasparek T, Venclikova S, Vrzalova M, Ceskova E. A detailed analysis of the effect of repetitive transcranial magnetic stimulation on negative symptoms of schizophrenia: a double-blind trial. Schizophr Res. 2013 Sep;149(1-3):167-73. doi: 10.1016/j.schres.2013.06.015. Epub 2013 Jun 25.
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: Sasaki N, Hara T, Yamada N, Niimi M, Kakuda W, Abo M. The Efficacy of High-Frequency Repetitive Transcranial Magnetic Stimulation for Improving Apathy in Chronic Stroke Patients. Eur Neurol. 2017;78(1-2):28-32. doi: 10.1159/000477440. Epub 2017 Jun 3.