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

Amyotrophic Lateral Sclerosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03892863
• Other study ID #: JagiellonianU61
• Status: Withdrawn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. 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.

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.

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)

• 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

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Depression
• Motor Neuron Disease
• Sclerosis

Intervention

Device:
• active repetitive transcranial magnetic stimulation
High frequency rTMS to induce the long term potentiation in the left dorsolateral prefrontal cortex
• sham repetitive transcranial magnetic stimulation
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 (5)

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

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. — 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

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

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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Before rTMS, directly (on the same day) after finishing rTMS
Primary	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.	Before rTMS, two weeks after finishing rTMS
Primary	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.	Before rTMS, four weeks after finishing rTMS
Secondary	Amyotrophic 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 the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised to the measurement taken directly after finishing rTMS.	Before rTMS, directly (on the same day) after finishing rTMS
Secondary	Amyotrophic 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.	Before rTMS, two weeks after finishing rTMS
Secondary	Amyotrophic 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 the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised to the measurement taken directly after finishing rTMS.	Before rTMS, four weeks after finishing rTMS
Secondary	Apathy Evaluation Scale Clinical Version ater rTMS, total score, range 18 to 72 with higher values representing a worse outcome	Change from baseline score in the Apathy Evaluation Scale Clinical Version to the measurement taken taken directly after finishing rTMS.	Before rTMS, directly (on the same day) after finishing rTMS
Secondary	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 the Apathy Evaluation Scale Clinical Version to the measurement taken two weeks after finishing rTMS.	Before rTMS, two weeks after finishing rTMS
Secondary	AES-C second follow up, total score, range 18 to 72 with higher values representing a worse outcome	Change from baseline score in the Apathy Evaluation Scale Clinical Version to the measurement taken four weeks after finishing rTMS.	Before rTMS, four weeks after finishing rTMS