Non-invasive Brain Stimulation for the Treatment of Depression Symptoms in ALS

Non-invasive Brain Stimulation for the Treatment of Depression Symptoms in ALS: A Pilot Study

This is an open-label clinical trial to determine the safety of rTMS and efficacy in improving depression symptoms, quality of life and cognition deficits among patients with Amyotrophic Lateral Sclerosis (ALS) and other neurodegenerative disorders.

Study Overview

• Status: Terminated
• Conditions: ALS
• Intervention / Treatment: Device: rTMS

Detailed Description

The objective of this study is to evaluate the role of repetitive transcranial magnetic stimulation (rTMS) for symptom reduction of depression and cognitive loss among patients with Amyotrophic Lateral Sclerosis (ALS) and other Neurodegenerative Diseases. Behavioral symptoms in ALS have been under scrutiny since its earliest descriptions, nearly 30 years ago (1). The importance of these symptoms among subjects with ALS has been also been under steady scrutiny. Studies have shown that the rates of anxiety and depression are significantly higher among subjects with ALS than the general population (1-23). Anxiety symptoms are related to depression, quality of life, and satisfaction with life (4, 9, 11, 15, 20, 24-26). Depressive symptoms are closely related to the ALS disease process (2).

rTMS has been shown to be a promising tool in modulating mood, memory, and cognitive performance (27). Current approaches to the management of ALS involve addressing symptomatology associated with the disease process. Among patients with ALS and other similar Neurodegenerative disorders, it is therefore important to understand if rTMS as an intervention is capable of:

1. Symptomatic improvement in mood,
2. Causing a significant positive change in disease progression or
3. Helping improve quality of life.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • Shara Holzberg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Diagnosis of familial or sporadic ALS as well as other Neurodegenerative disorders. Verification of the diagnosis will be performed by the Principal Investigator. This diagnosis can include neuro-degenerative disorders of uncertain cause, including ALS, MND, Peripheral neuropathies, Parkinson's and other progressive motor system diseases.
2. If subjects has ALS diagnosis, the date of dx should be ≤ 2 years
3. Age 18 or older.
4. Capable of providing informed consent.
5. Minimal speech impairment.
6. Ability to comply with study procedures.
7. Ability to communicate clearly if the subject wants to withdraw from the procedure at any stage.
8. MMSE ≥20

9. Female subjects of child bearing potential must engage in abstinence for the duration of the study. If a participant becomes sexually active, she must agree to using the following birth control methods:

   1. Hormonal (oral, implanted, injected, etc)
   2. Intrauterine device in place for ≥ 3 months
   3. Adequate barrier method in conjunction with spermicide
   4. Other
10. Absence of exclusion criteria.

EExclusion Criteria

1. Unable to provide informed consent
2. Significant speech impairment
3. Inability to comply with the procedures
4. Subjects with ALS diagnosis ≥ 2 years
5. Inability to communicate clearly if the subject wants to withdraw from the procedure at any stage
6. Seizures or history of seizures
7. Patients who have underwent brain surgery for any indication
8. Patients with pacemakers, cochlear implants, brain stimulators, infusion pumps, intracardiac lines, metallic clips, other implanted electronic or ferroelectric metallic devices. Dental implants are permitted
9. Inability to perform either TMS or NCS studies due to insufficient MEP or CMAP amplitude.
10. Patients with uncontrolled hypertension
11. Patients with neuro endocrine disorders

12. Patients who are withdrawn from the following drugs within 6 months:

    • Barbiturates
    • Benzodiazepines
    • Meprobamate
    • Chloral hydrate

Patients who have a recent history (within 24h) or chronic history of intake of:

• Cocaine.
• Phencyclidine Phosphate.
• Gamma-Hydroxy Butyrate.

• Amphetamines including N-methylamphetamine, 3,4-Methylenedioxymethamphetamine, 2,5-dimethoxy-4-methylamphetamine, Ephedrine, Cathinone.

  12. Substance abuse+ 13. Excessive use of alcohol # 14. MMSE ≤19 15. Female patients of child bearing potential not practicing contraception 16. Female patients who are pregnant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: intervention; rTMS	Device: rTMS; repetitive transcranial magnetic stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate safety and efficacy of repetitive transcranial magnetic stimulation (rTMS) using the FDA approved protocol in research subjects with ALS and other Neurodegenerative disorders.	Transcranial magnetic stimulation (TMS) is a non-invasive procedure used to stimulate small regions of the brain. It is a FDA approved for treatment resistant depression (K061053). We hypothesize that stimulation of dorsolateral prefrontal cortex (DLPFC) will be safe and effective in patients with ALS and other Neurodegenerative disorders. We will follow the FDA rTMS guidance for industry guidelines. All adverse events from all 15 patients enrolled in the study as assessed by the CTCAE v4.0, and as well, any occurrence of any new seizure in 2 or more patients, as reviewed and assessed by PI and medical monitor.	over 4 weeks, done once a week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To understand the impact of rTMS in addressing the mood symptoms associated with ALS.	rTMS is known to ameliorate depressive symptoms in patients with treatment resistant depression. It may also ameliorate depressive symptoms in subjects with ALS. This is measured using MQOL (Montreal Quality of life scale). This is a patient-reported instrument designed to assess overall well-being over a two day time scale. this single item scale is scored from 0-10 with higher score representing higher quality of life ratings. percent change from baseline to study completion will be measured to assess the efficacy of rtms in improving overall quality of life.	recorded once a week for the 4 week duration of the study.

Collaborators and Investigators

• Sponsor: Hospital for Special Surgery, New York

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 29, 2017
• Primary Completion (ACTUAL): August 16, 2022
• Study Completion (ACTUAL): August 16, 2022

Study Registration Dates

• First Submitted: November 30, 2017
• First Submitted That Met QC Criteria: December 11, 2017
• First Posted (ACTUAL): December 14, 2017

Study Record Updates

• Last Update Posted (ACTUAL): November 14, 2022
• Last Update Submitted That Met QC Criteria: November 9, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Depression
• Other Study ID Numbers: 2016-0326

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes