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

Amyotrophic Lateral Sclerosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03892382
• Other study ID #: JagiellonianU62
• Status: Withdrawn
• Phase: N/A
• Start date: November 15, 2019
• Est. completion date: December 31, 2021

Study information

• Verified date: February 2020
• Source: Jagiellonian University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 31, 2021
• Est. primary completion date: June 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

Intervention

Device:
• rTMS
High frequency rTMS to induce the long term potentiation in the left dorsolateral prefrontal cortex.

Locations

Country	Name	City	State
Poland	Jagiellonian University Medical College, Department of Neurology	Kraków

Sponsors (1)

Lead Sponsor	Collaborator
Jagiellonian University

Country where clinical trial is conducted

Poland, 

References & Publications (9)

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. Review. — View 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. — View 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. — View Citation

Lefaucheur JP, André-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, Jääskeläinen SK, Kimiskidis VK, Koch G, Langguth B, Nyffeler T, Oliviero A, Padberg F, Poulet E, Rossi S, Rossini PM, Rothwell JC, Schönfeldt-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. Review. — View 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. — View 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. — View 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. — View 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. Review. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Apathy Evaluation Scale Clinical Version after rTMS, total score, range 18 to 72 with higher values representing a worse outcome	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
Primary	Apathy Evaluation Scale Clinical Version first follow up, total score, range 18 to 72 with higher values representing a worse outcome	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
Primary	Apathy Evaluation Scale Clinical Version second follow up, total score, range 18 to 72 with higher values representing a worse outcome	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	Lateral Sclerosis Functional Rating Scale-Revised after rTMS, total score, range 0 to 40 with higher values representing a better outcome	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
Secondary	Lateral Sclerosis Functional Rating Scale-Revised first follow up, total score, range 0 to 40 with higher values representing a better outcome	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
Secondary	Lateral Sclerosis Functional Rating Scale-Revised second follow up, total score, range 0 to 40 with higher values representing a better outcome	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
Secondary	Beck's Depression Inventory ater rTMS, total score, range 0 to 63, with higher values representing a worse outcome	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
Secondary	Beck's Depression Inventory first follow up, total score, range 0 to 63, with higher values representing a worse outcome	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
Secondary	Beck's Depression Inventory second follow up, total score, range 0 to 63, with higher values representing a worse outcome	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