Serial Fasciculation Measurements in Motor Neurone Disease

Sequential High-density Surface Electromyography (HDSEMG) Recordings in Motor Neurone Disease: Fasciculations as a Biomarker of Motor Neurone Health

Patients with motor neurone disease (MND) typically experience relentless motor decline and die within three years of symptom onset from respiratory muscle weakness. There are currently no effective therapies and the discovery of novel therapies is hampered by the lack of a sensitive disease biomarker. Consequently, there is a huge drive to discover novel biomarkers, which can reliably track disease progression over time. These can then be incorporated into clinical drug trials to expedite effective drug discovery.

Muscle fasciculations represent the hyperexcitability of diseased motor neurons and are almost universally present from the early stages of MND. The investigators predict that the site, frequency and shape of fasciculations might provide a sensitive measure of disease progression in an individual.

In order to calibrate this technique, the investigators will conduct a 12-month longitudinal study, recruiting 24 patients from the King's College Hospital Motor Nerve Clinic, comprising a mixture of patients with MND and those with benign fasciculation syndrome. Patients in this latter group have fasciculations but do not develop weakness and have normal lifespans. They are therefore an optimal control group. At each visit, the investigators will take resting HDSEMG recordings from all four limbs and perform standard clinical measures of disease progression. The investigators will also monitor the decline in motor unit number using a newly validated neurophysiological technique, called Motor Unit Number Index (MUNIX).

Study Overview

• Status: Completed
• Conditions: Motor Neuron Disease; Benign Fasciculation-Cramp Syndrome
• Intervention / Treatment: Device: High-density surface electromyography

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom
    • King's College Hospital NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria for MND patients:

(i) Aged between 40 and 80 years of age inclusive, at the time of signing the informed consent.

(ii) Diagnosed with MND by a neurologist with expertise in MND.(20) For subjects with bulbar onset there must be objective limb involvement of at least one limb.

(iii) Diagnosed with MND within 24 months of symptom onset. (iv) Subjects must be ambulatory (i.e. must not be confined to a wheelchair). (v) Male and female subjects (vi) Capable of giving signed informed consent (vii) Capable and willing to comply with the requirements of the protocol (either by themselves or with assistance).

Inclusion criteria for Benign Fasciculation Syndrome (BFS) patients:

(i) Aged between 18 and 80 years of age inclusive, at the time of signing the informed consent.

(ii) Diagnosed with BFS by a neurologist with expertise in motor nerve disorders.

(iii) Male and female subjects (vi) Capable of giving signed informed consent (vii) Capable and willing to comply with the requirements of the protocol (either by themselves or with assistance).

Exclusion criteria for MND patients:

(i) Neurological (other than the subject's MND) or non-neurological co-morbidities (e.g. joint disease, respiratory disease) which limit mobility.

(ii) Clinically significant cognitive impairment in the opinion of the investigator or lacking capacity in accordance with the Mental Capacity Act (2005).

(iii) Regionally restricted forms of MND, or other atypical variants:

• Isolated corticobulbar pattern of MND with normal ambulation
• Primary lateral sclerosis
• Signs of chronic partial denervation restricted to a single limb

• MND or parkinsonism dementia complex (iv) Subjects requiring mechanical ventilation (non-invasive ventilation for sleep apnoea is allowed).

  (v) Historical or current evidence of clinically significant uncontrolled disease which, in the opinion of the chief investigator, would put the safety of the subject at risk through participation or impact the study assessments or endpoints.

(vi) Presence of an active implantable cardiac medical device (e.g., pacemaker or implantable cardioverter-defibrillator) or at a high risk for needing external defibrillation.

(vii) History of skin hypersensitivity to adhesives. (viii) Current participation in a clinical trial which in the opinion of the chief investigator might impact the objectives of this study.

Exclusion criteria for Benign Fasciculation Syndrome patients:

(i) Significant diagnostic uncertainty, whereby motor neurone disease remains a possible differential diagnosis.

(ii) Historical or current evidence of clinically significant uncontrolled disease which, in the opinion of the chief investigator, would put the safety of the subject at risk through participation or impact the study assessments or endpoints.

(iii) Presence of an active implantable cardiac medical device (e.g., pacemaker or implantable cardioverter-defibrillator) or at a high risk for needing external defibrillation.

(iv) History of skin hypersensitivity to adhesives. (v) Current participation in a clinical trial which in the opinion of the chief investigator might impact the objectives of this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Motor neuron disease	Device: High-density surface electromyography; High-density surface electromyography
Active Comparator: Benign fasciculation syndrome	Device: High-density surface electromyography; High-density surface electromyography

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in fasciculation frequency over time	To characterise the frequency of fasciculations in patients with motor neurone disease and to determine whether these parameters correlate with the trajectory of disease progression over a 12-month period.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in fasciculation morphology over time		12 months
Change in Functional Rating Scale (FRS) over time	Maximum score of 48; lower scores indicate worse disability	12 months
Change in motor unit number index measurements over time		12 months
Change in MRC power sum score over time		12 months
Change in slow vital capacity over time		12 months

Collaborators and Investigators

• Sponsor: King's College Hospital NHS Trust

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2017
• Primary Completion (Actual): March 1, 2019
• Study Completion (Actual): March 1, 2019

Study Registration Dates

• First Submitted: March 13, 2018
• First Submitted That Met QC Criteria: January 17, 2019
• First Posted (Actual): January 18, 2019

Study Record Updates

• Last Update Posted (Actual): August 21, 2019
• Last Update Submitted That Met QC Criteria: August 20, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neurodegenerative Diseases; Neuromuscular Manifestations; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Neuromuscular Diseases; Fasciculation
• Other Study ID Numbers: KCH17-105

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No