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

NCT03892863 | Withdrawn

• 1 other identifier: JagiellonianU61
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Amyotrophic Lateral Sclerosis

Keywords

Amyotrophic Lateral Sclerosis; depression; rTMS

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• 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 Outcomes (6)

• Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised after rTMS, total score, range 0 to 40 with higher values representing a better outcome

  Before rTMS, directly (on the same day) after finishing rTMS

• Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised first follow up, total score, range 0 to 40 with higher values representing a better outcome

  Before rTMS, two weeks after finishing rTMS

• Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised second follow up, total score, range 0 to 40 with higher values representing a better outcome

  Before rTMS, four weeks after finishing rTMS

• Apathy Evaluation Scale Clinical Version ater rTMS, total score, range 18 to 72 with higher values representing a worse outcome

  Before rTMS, directly (on the same day) after finishing rTMS

• Apathy Evaluation Scale Clinical Version first follow up, total score, range 18 to 72 with higher values representing a worse outcome

  Before rTMS, two weeks after finishing rTMS

Study Arms (2)

active repetitive transcranial magnetic stimulation

ACTIVE COMPARATOR

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.

Device: active repetitive transcranial magnetic stimulation

sham repetitive transcranial magnetic stimulation

SHAM COMPARATOR

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.

Device: sham repetitive transcranial magnetic stimulation

Interventions

active repetitive transcranial magnetic stimulation DEVICE

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

active repetitive transcranial magnetic stimulation

sham repetitive transcranial magnetic stimulation DEVICE

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

sham repetitive transcranial magnetic stimulation

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Jagiellonian University: lead

Study Sites (1)

Jagiellonian University Medical College, Department of Neurology

Krakow, 31503, Poland

Location

Related 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. doi: 10.1080/146608200300079536. No abstract available.

  PMID: 11464847 BACKGROUND

• 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.

  PMID: 15258224 BACKGROUND

• 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.

  PMID: 25034472 BACKGROUND

• 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.

  PMID: 19833552 BACKGROUND

• 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.

  PMID: 28092847 BACKGROUND

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis; Depression

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Behavioral Symptoms; Behavior

Study Officials

• Jakub M Antczak, MD

  Department of Neurology, Jagiellonian University Medical College

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Sham stimulation will be provided by holding the stimulating coil perpendicularly to the scalp, which assures similar impression as during active stimulation but prevents significant magnetic field to reach the brain tissue.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Patients will be randomly assigned to real or placebo (sham) stimulation.

Study Record Dates

• First Submitted: March 26, 2019
• First Posted: March 27, 2019
• Study Start: November 15, 2019
• Primary Completion: June 30, 2021
• Study Completion: December 31, 2021
• Last Updated: February 10, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: The data will become available after the study is published.
• Access Criteria: On request send by e-mail: jantczak@cm-uj.krakow.pl

Locations

PL (1)