Neuromuscular Magnetic Stimulation in ALS Patients

NCT03618966 | Completed Phase 2 DMC

• 1 other identifier: 2174
• Study Type: interventional
• Target: 22
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

Amyotrophic Lateral Sclerosis

Keywords

Amyotrophic lateral sclerosis; Muscle disease; Neuromuscular magnetic stimulation

Outcome Measures

Primary Outcomes (1)

• Change from baseline to Week 2 in the muscle strength measured by Medical Research Council Muscle Scale (MRC).

  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 Outcomes (6)

• Change from baseline to Week 2 in the muscle strength measured by handgrip dynamometry

  Baseline to Week 2

• Change from baseline to Week 2 in the Compound Muscle Action Potential (CMAP) amplitude from flexor carpi radialis

  Baseline to Week 2

• Change from baseline to Week 2 in the amplitude of the ACh-evoked currents (IACh) for nicotinic acetylcholine receptors

  Baseline to Week 2

• Change from baseline to Week 2 on levels of insulin-like growth factor-1 (IGF-1) and Myostatin

  Baseline to Week 2

• Change from baseline to Week 2 on the diameter size of muscle fibers

  Baseline to Week 2

Study Arms (2)

Right-real NMMS Group

EXPERIMENTAL

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)

Left-real NMMS Group

ACTIVE COMPARATOR

It will receive a rNMMS of the left arm and a sNMMS of the right arm

Device: Neuromuscular magnetic stimulation (NMMS)

Interventions

Neuromuscular magnetic stimulation (NMMS) DEVICE

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.

Left-real NMMS Group; Right-real NMMS Group

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Roma La Sapienza: lead

Related Publications (13)

• Musaro A. Understanding ALS: new therapeutic approaches. FEBS J. 2013 Sep;280(17):4315-22. doi: 10.1111/febs.12087. Epub 2013 Jan 3.

  PMID: 23217177 BACKGROUND

• Taylor JP, Brown RH Jr, Cleveland DW. Decoding ALS: from genes to mechanism. Nature. 2016 Nov 10;539(7628):197-206. doi: 10.1038/nature20413.

  PMID: 27830784 BACKGROUND

• Dadon-Nachum M, Melamed E, Offen D. The "dying-back" phenomenon of motor neurons in ALS. J Mol Neurosci. 2011 Mar;43(3):470-7. doi: 10.1007/s12031-010-9467-1. Epub 2010 Nov 7.

  PMID: 21057983 BACKGROUND

• Dupuis L, Loeffler JP. Neuromuscular junction destruction during amyotrophic lateral sclerosis: insights from transgenic models. Curr Opin Pharmacol. 2009 Jun;9(3):341-6. doi: 10.1016/j.coph.2009.03.007. Epub 2009 Apr 20.

  PMID: 19386549 BACKGROUND

• Dobrowolny G, Aucello M, Rizzuto E, Beccafico S, Mammucari C, Boncompagni S, Belia S, Wannenes F, Nicoletti C, Del Prete Z, Rosenthal N, Molinaro M, Protasi F, Fano G, Sandri M, Musaro A. Skeletal muscle is a primary target of SOD1G93A-mediated toxicity. Cell Metab. 2008 Nov;8(5):425-36. doi: 10.1016/j.cmet.2008.09.002.

  PMID: 19046573 BACKGROUND

• Loeffler JP, Picchiarelli G, Dupuis L, Gonzalez De Aguilar JL. The Role of Skeletal Muscle in Amyotrophic Lateral Sclerosis. Brain Pathol. 2016 Mar;26(2):227-36. doi: 10.1111/bpa.12350.

  PMID: 26780251 BACKGROUND

• Palma E, Inghilleri M, Conti L, Deflorio C, Frasca V, Manteca A, Pichiorri F, Roseti C, Torchia G, Limatola C, Grassi F, Miledi R. Physiological characterization of human muscle acetylcholine receptors from ALS patients. Proc Natl Acad Sci U S A. 2011 Dec 13;108(50):20184-8. doi: 10.1073/pnas.1117975108. Epub 2011 Nov 29.

  PMID: 22128328 BACKGROUND

• Palma E, Reyes-Ruiz JM, Lopergolo D, Roseti C, Bertollini C, Ruffolo G, Cifelli P, Onesti E, Limatola C, Miledi R, Inghilleri M. Acetylcholine receptors from human muscle as pharmacological targets for ALS therapy. Proc Natl Acad Sci U S A. 2016 Mar 15;113(11):3060-5. doi: 10.1073/pnas.1600251113. Epub 2016 Feb 29.

  PMID: 26929355 BACKGROUND

• Kern H, Barberi L, Lofler S, Sbardella S, Burggraf S, Fruhmann H, Carraro U, Mosole S, Sarabon N, Vogelauer M, Mayr W, Krenn M, Cvecka J, Romanello V, Pietrangelo L, Protasi F, Sandri M, Zampieri S, Musaro A. Electrical stimulation counteracts muscle decline in seniors. Front Aging Neurosci. 2014 Jul 24;6:189. doi: 10.3389/fnagi.2014.00189. eCollection 2014.

  PMID: 25104935 BACKGROUND

• Eusebi F, Palma E, Amici M, Miledi R. Microtransplantation of ligand-gated receptor-channels from fresh or frozen nervous tissue into Xenopus oocytes: a potent tool for expanding functional information. Prog Neurobiol. 2009 May;88(1):32-40. doi: 10.1016/j.pneurobio.2009.01.008. Epub 2009 Feb 7.

  PMID: 19428960 BACKGROUND

• Musaro A, McCullagh K, Paul A, Houghton L, Dobrowolny G, Molinaro M, Barton ER, Sweeney HL, Rosenthal N. Localized Igf-1 transgene expression sustains hypertrophy and regeneration in senescent skeletal muscle. Nat Genet. 2001 Feb;27(2):195-200. doi: 10.1038/84839.

  PMID: 11175789 BACKGROUND

• Scicchitano BM, Rizzuto E, Musaro A. Counteracting muscle wasting in aging and neuromuscular diseases: the critical role of IGF-1. Aging (Albany NY). 2009 May 13;1(5):451-7. doi: 10.18632/aging.100050.

  PMID: 20157530 BACKGROUND

• Trendelenburg AU, Meyer A, Rohner D, Boyle J, Hatakeyama S, Glass DJ. Myostatin reduces Akt/TORC1/p70S6K signaling, inhibiting myoblast differentiation and myotube size. Am J Physiol Cell Physiol. 2009 Jun;296(6):C1258-70. doi: 10.1152/ajpcell.00105.2009. Epub 2009 Apr 8.

  PMID: 19357233 BACKGROUND

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis; Muscular Diseases

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; Musculoskeletal Diseases

Study Officials

• Maurizio Inghilleri, Prof

  Department of Human Neuroscience, Umberto I Hospital-University of Rome Sapienza

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: All the electrophysiological experiments will be performed in double-blind fashion.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: Patients will be randomized in two groups by receiving a sequential number according to a from a computer-generated random list. A first group will receive a real stimulation (rNMMS) of the right arm and a sham stimulation (sNMMS) of the left arm; a second group received a rNMMS of the left arm and a sNMMS of the right arm. Every cycle of stimulation will last two weeks. All patients will undergo a medial nerve conduction study (NCS) and a clinical evaluation before and at the end of the treatment and another evaluation after two weeks after the end of treatment. Clinical examination will include i) handgrip strength test for the measure of maximal isometric strength of hand and flexor forearm muscles; ii) MRC Muscle Scale for manual muscular testing of the upper limbs. At the end of the stimulation procedure, a needle muscle biopsy under a local anesthetic will be performed bilaterally from flexor carpi radialis muscle for histological, physiological and molecular studies.

Study Record Dates

• First Submitted: July 23, 2018
• First Posted: August 7, 2018
• Study Start: November 1, 2014
• Primary Completion: May 1, 2016
• Study Completion: November 1, 2017
• Last Updated: August 7, 2018

Record last verified: 2018-08