Neuromuscular Magnetic Stimulation in ALS Patients (NMS-ALS)

August 1, 2018 updated by: Maurizio Inghilleri, University of Roma La Sapienza

Neuromuscular Magnetic Stimulation Counteracts Muscle Decline in ALS Patients

Aim of the study is to verify whether neuromuscular magnetic stimulation can improve muscle function in spinal-onset Amyotrophic Lateral Sclerosis (ALS) patients.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Background: Amyotrophic lateral sclerosis (ALS) is a multi-factorial and multi-systemic pathology associated with motor neuron degeneration, muscle atrophy and paralysis. Mounting evidence suggests that the earliest presymptomatic functional and pathological changes are occurring distally in axons and at the neuromuscular junction (NMJ). These changes precede, and can be independent of the loss of cell bodies or alterations in other cell types already linked to the ALS disease process. In line with these studies, we found that in human ALS muscles the acetylcholine receptors (AChRs) are less sensitive to ACh than denervated non-ALS muscles. It has been also reported that muscle specific expression of mutant superoxide dismutase (SOD1) gene induces muscle atrophy, significant reduction in muscle strength, mitochondrial dysfunction, microgliosis, and neuronal degeneration, suggesting that retrograde signals from muscle to nerve may contribute to synapse and axon damage. This suggests that skeletal muscle is an important target for therapeutic intervention. Neuromuscular system may be artificially stimulated either by an electrical stimulation (ES) or by time-varying electromagnetic fields. Neuromuscular magnetic stimulation (NMMS) has been proposed as an alternative, non-invasive, stimulation technique.

Objective: aim of the study is to verify whether neuromuscular magnetic stimulation can improve muscle function in spinal-onset Amyotrophic Lateral Sclerosis (ALS) patients. We will study if neuromuscular magnetic stimulation can counteract muscle atrophy by promoting the modulation of factors associated with muscle catabolism and/or increasing the efficacy of nicotinic acetylcholine receptors.

Methods: At the baseline visit, ALS patients will be randomized in two groups to receive daily real neuromuscular magnetic stimulation in one arm and sham neuromuscular magnetic stimulation in the opposite arm for two weeks. All patients will undergo median nerve conduction study and a clinical examination, including handgrip strength test and evaluation of upper limbs muscle strength by Medical Research Council Muscle Scale. At the end of the stimulation procedures, a needle muscle biopsy will be performed bilaterally from flexor carpi radialis muscle. Muscle samples will be used to perform histomorphometric and molecular analysis and electrophysiological recordings of acetylcholine evoked currents.

Study Type

Interventional

Enrollment (Actual)

22

Phase

  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • diagnosis of probable or definite ALS with spinal-onset
  • right-handed patients
  • a bilateral symmetric muscular deficit in flexor carpi radialis muscle or flexor digitorum profundus muscle (defined by a MRC Muscle Scale score of 3-4/5)

Exclusion Criteria:

  • history of epilepsy or severe headaches,
  • pregnancy or breast-feeding
  • patients with implanted cardiac pacemaker, neurostimulators, surgical clips or medical pumps
  • presenting any other comorbid condition affecting the possibility of completing the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Right-real NMMS Group
It will receive a real stimulation (rNMMS) of the right arm and a sham stimulation (sNMMS) of the left arm
Device: Neuromuscular magnetic stimulation (NMMS)
It is a non-invasive, stimulation technique that does not induce high-intensity cutaneous electric fields and does not activate skin nociceptors, thus resulting in a painless and better-tolerated procedure. rNMMS is delivered through a high-frequency magnetic stimulator connected to a conventional circular cooled coil. Magnetic stimulator is placed above the flexor muscles of the forearm. rNMMS is delivered at a 5-Hz frequency and with a 100% stimulation intensity of 100% of the maximum intensity in 140 trains of 50 stimuli. sNMMS is delivered with a sham coil producing similar acoustic sensations and mechanical skin perceptions.
Active Comparator: Left-real NMMS Group
It will receive a rNMMS of the left arm and a sNMMS of the right arm
Device: Neuromuscular magnetic stimulation (NMMS)
It is a non-invasive, stimulation technique that does not induce high-intensity cutaneous electric fields and does not activate skin nociceptors, thus resulting in a painless and better-tolerated procedure. rNMMS is delivered through a high-frequency magnetic stimulator connected to a conventional circular cooled coil. Magnetic stimulator is placed above the flexor muscles of the forearm. rNMMS is delivered at a 5-Hz frequency and with a 100% stimulation intensity of 100% of the maximum intensity in 140 trains of 50 stimuli. sNMMS is delivered with a sham coil producing similar acoustic sensations and mechanical skin perceptions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline to Week 2 in the muscle strength measured by Medical Research Council Muscle Scale (MRC).
Time Frame: Baseline to Week 2
Evaluation of the efficacy of NMMS in improving the muscular strength in ALS patients as measured by MRC-score (numeric scale, normal value: 35 for upper limbs, 40 for lower limbs).
Baseline to Week 2

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline to Week 2 in the muscle strength measured by handgrip dynamometry
Time Frame: Baseline to Week 2
Evaluation of the efficacy of NMMS in improving the muscular strength in ALS patients as measured by handgrip dynamometry (numeric scale, normal value: >35 for female, >45 for male)
Baseline to Week 2
Change from baseline to Week 2 in the Compound Muscle Action Potential (CMAP) amplitude from flexor carpi radialis
Time Frame: Baseline to Week 2
Evaluation of the effect of NMMS on the electrophysiological parameter (CMAP) to analyse the physiological mechanisms of the applied neurophysiological technique (milliVolt, mV, normal value 10.2 mV).
Baseline to Week 2
Change from baseline to Week 2 in the amplitude of the ACh-evoked currents (IACh) for nicotinic acetylcholine receptors
Time Frame: Baseline to Week 2
Evaluation of the effect of NMMS on the nicotinic acetylcholine receptor in patients with ALS (nanoAmpere, nA)
Baseline to Week 2
Change from baseline to Week 2 on levels of insulin-like growth factor-1 (IGF-1) and Myostatin
Time Frame: Baseline to Week 2
Evaluation of the effect of NMMS on the adaptation changes of gene expression due to rNMMS quantifying shifts in messenger ribonucleic acid (mRNA) levels of a selected panel of genes involved in muscle growth (numeric value)
Baseline to Week 2
Change from baseline to Week 2 on the diameter size of muscle fibers
Time Frame: Baseline to Week 2
Evaluation of the effect of NMMS on histomorphometric analysis in ALS muscle fibers (micrometer, μm).
Baseline to Week 2
Change from baseline to Week 2 on levels of Muscle Atrophy F-box (MAFbx)/Atrogin-1 and Muscle Ring-Finger Protein 1 (MuRF-1)
Time Frame: Baseline to Week 2
Evaluation of the effect of NMMS on the adaptation changes of gene expression due to rNMMS quantifying shifts in mRNA levels of a selected panel of genes involved in downregulation of atrophy-related genes (numeric value)
Baseline to Week 2

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Roma La Sapienza

Investigators

  • Principal Investigator: Maurizio Inghilleri, Prof, Department of Human Neuroscience, Umberto I Hospital-University of Rome Sapienza

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2014

Primary Completion (Actual)

May 1, 2016

Study Completion (Actual)

November 1, 2017

Study Registration Dates

First Submitted

July 23, 2018

First Submitted That Met QC Criteria

August 1, 2018

First Posted (Actual)

August 7, 2018

Study Record Updates

Last Update Posted (Actual)

August 7, 2018

Last Update Submitted That Met QC Criteria

August 1, 2018

Last Verified

August 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2174

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

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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