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

NCT03892382 | Withdrawn

• 1 other identifier: JagiellonianU62
• 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. 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.

Conditions

Amyotrophic Lateral Sclerosis

Keywords

Amyotrophic Lateral Sclerosis; rTMS; apathy; depression

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• 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 Outcomes (6)

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

  Baseline rTMS, directly (on the same 1 day) after finishing rTMS

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

  Baseline rTMS, two weeks after finishing rTMS

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

  Baseline rTMS, four weeks after finishing rTMS

• Beck's Depression Inventory ater rTMS, total score, range 0 to 63, with higher values representing a worse outcome

  Baseline rTMS, directly (on the same 1 day) after finishing rTMS

• Beck's Depression Inventory first follow up, total score, range 0 to 63, with higher values representing a worse outcome

  Baseline rTMS, two weeks after finishing rTMS

Study Arms (2)

Active rTMS

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: rTMS

Sham rTMS

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: rTMS

Interventions

rTMS DEVICE

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

Active rTMS; Sham rTMS

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)
• Moderate or severe depression defined as the score in Beck's Depression Inventory ≥20
• 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 (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. doi: 10.1080/146608200300079536. No abstract available.

  PMID: 11464847 BACKGROUND

• 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.

  PMID: 29189922 BACKGROUND

• 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.

  PMID: 26822417 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

• 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.

  PMID: 28161090 BACKGROUND

• 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.

  PMID: 29331848 BACKGROUND

• 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.

  PMID: 23810122 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

• 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.

  PMID: 28578330 BACKGROUND

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis; Lethargy; 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; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; 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)