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

NCT ID: NCT03892863

Last Updated: 2020-02-10

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: NA
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-11-15
• Study Completion Date: 2021-12-31

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.

Conditions

Amyotrophic Lateral Sclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

active repetitive transcranial magnetic stimulation

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.

Group Type: ACTIVE_COMPARATOR

active repetitive transcranial magnetic stimulation

Intervention Type: DEVICE

High frequency rTMS to induce the long term potentiation in the left dorsolateral prefrontal cortex

sham repetitive transcranial magnetic stimulation

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.

Group Type: SHAM_COMPARATOR

sham repetitive transcranial magnetic stimulation

Intervention Type: DEVICE

High frequency rTMS to induce the long term potentiation in the left dorsolateral prefrontal cortex

Interventions

active repetitive transcranial magnetic stimulation

High frequency rTMS to induce the long term potentiation in the left dorsolateral prefrontal cortex

Intervention Type: DEVICE

sham repetitive transcranial magnetic stimulation

High frequency rTMS to induce the long term potentiation in the left dorsolateral prefrontal cortex

Intervention Type: DEVICE

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jagiellonian University

OTHER

Sponsor Role: lead

Responsible Party

Jakub Antczak

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jakub M Antczak, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Neurology, Jagiellonian University Medical College

Locations

Jagiellonian University Medical College, Department of Neurology

Krakow, , Poland

Countries

Poland

References

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.

Reference Type: BACKGROUND

PMID: 11464847 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15258224 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25034472 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19833552 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 28092847 (View on PubMed)

Other Identifiers

JagiellonianU61

Identifier Type: -

Identifier Source: org_study_id