The Neuroimage Study of the Neuromuscular Disorders.

Neuromuscular Diseases Clinical Trial

Official title:

The Neuroimage Study of the Neuromuscular Disorders.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05048862
• Other study ID #: 201705058RIND
• Status: Recruiting
• Start date: August 1, 2021
• Est. completion date: August 1, 2031

Study information

• Verified date: October 2023
• Source: National Taiwan University Hospital
• Contact: Hsueh-Wen Hsueh, MD, MMS
• Phone: +886-223123456
• Email: 102194[@]ntuh.gov.tw
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

The neuromuscular disorders could be briefly divided to neuropathy, myopathy, motor neuron disease, and neuromuscular junction disorder. In the past, the evaluation of the neuromuscular disorders depended on several ways (ex. electrodiagnostic studies and biopsy) to evaluate the pathophysiology and the pathological change. However, due to the issue of resolution, few image studies were available to evaluate the structure for clinical practice. With the growing techniques, there are two ways to see the nerve and muscle in vivo, the magnetic resonance imaging (MRI) and the ultrasonography. The availability of the machine, the high cost, inability to change the position for dynamic views of the nerves, and the relative invasion considering the large energy penetrating the patient might limit the clinical use of MRI. The nerve ultrasonography is a safe and easily available technique. The development of high-frequency transducers has led to an improvement in the resolution of ultrasonography and enables the exploration of peripheral nerve and muscle structural changes. In additional to evaluate the morphological changes, ultrasonography has been used extensively for the vessel status assessment through duplex ultrasound. In present study, we will apply variable approaches, including to muscle, nerve, and skin biopsy, electrophysiological study, quantitative sensory testing, autonomic functional tests, pain evoked potentials, MRI, and ultrasonography to integrally investigate the different aspects of neuromuscular disorders. The results of the study will provide integrated insights of (1) the neurophysiology of nerve and vessels and (2) pathogenesis of different neuromuscular disorders.

Description:

This is a prospective observational study which will be performed in both the inpatient and outpatient setting of National Taiwan University Hospital. Patients age at least 20 years, and have been diagnosed as neuromuscular disorders by the neurologist. Patients who are unable to read the questionnaire, fail to accept all the examinations, and refuse to provide inform consent are excluded from this study. The normal group (age at least 20 years) who had no neurological symptoms or signs were also recruited. The neurological examination performed by the board neurologist must be normal in the normal group.

Different interventions were performed periodically to see the serial change. The interval between the interventions is within 1 month and there is no new symptoms or any events.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: August 1, 2031
• Est. primary completion date: August 1, 2031
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years and older

Eligibility

Inclusion Criteria (Neuromuscular group):

• been diagnosed as neuromuscular disorders by the neurologist

• at least 20-year-old

Inclusion Criteria (Normal group):

• no past history of neurological disorders.

• The neurological examination performed by the board neurologist must be normal

• at least 20-year-old

Exclusion Criteria (Neuromuscular and normal group):

• Patients who are unable to read the questionnaire, fail to accept all the examinations, and refuse to provide inform consent

Related Conditions & MeSH terms

• Neuromuscular Diseases

Intervention

Diagnostic Test:
• Neuromuscular ultrasound
Ultrasound will be performed with the Affiniti 70 (Philips Medical Instruments, Bothell, WA). all patients following standardized methods of our hospital. All the patient would be checked the skin surface temperature before the ultrasound examination. The image would be exported from the echo machine as DICOM format.
• Muscle MRI
Muscle MRI will be performed on a 3-T MR machine (Trio; Siemens, Erlangen, Germany). Each subject will lie in a supine position comfortably, supplied with ear plugs. A high resolution T1 weighted scan and Short-T1 Inversion Recovery series (STIR) of the four limbs muscle were obtained in axial and coronal plane. MR spectroscopy in interested muscle was also sampled to evaluate the composition of fat, water, lactate, and other studied molecules.
• Nerve conduction studies and autonomic function tests
Nerve conduction study will be performed with a Nicolet Viking IV Electromyographer (Madison, WI) in all patients following standardized methods recommended by the Consensus Development Conference on Standardized Measures in Diabetic Neuropathy. Studied nerves include sural, peroneal, tibial, median and ulnar (motor and sensory) nerves.Autonomic functions will be assessed by the SSR and RRIV with established protocol by using Nicolet Viking IV Electromyographer (Madison, WI).
• Quantitative sensory test
Quantative sensory test will be performed with a Thermal Sensory Analyzer and Vibratory Sensory Analyzer (Medoc Advanced Medical System, Minneapolis, MN). The procedure is the same as previously described 25. Briefly, the machine delivers to the patient a stimulus of constant intensity which is pre-set by the algorithm. By adjusting the intensity of stimulus (increase or decrease the intensity by a fixed ratio) according to the response of the subject (i.e. whether the subject perceives the stimulus or not), sensory thresholds of the warm, cold and vibratory modalities will be measured.
• Skin biopsy
A skin specimen of 3 mm in diameter will be taken with a biopsy punch from the lateral side of the distal leg under 2% lidocaine local anaesthesia 26. No suturing is required, and the wounds are covered with a piece of gauze. Wound healing takes 7~10 days, similar to a typical abrasion wound. Informed consent will be obtained from each patient before the skin biopsy. The intraepidermal nerve fiber density and sweat gland nerve innervation will be examined.
• Muscle and nerve biopsy
Two muscle specimens with 5 x 5 x 5 mm were collected in an open muscle biopsy or needle biopsy at studied muscles under 2% lidocaine local anaesthesia. The wound was about 2-3 cm long, and suture was required. Would healing usually takes 10-14 days. First specimen was undergoing snap freezing fixation in a longitudinal axis perpendicular to the cork with the liquid nitrogen and isopentane. The second specimen was divided into two equiponderous tissues, and one was freezed in liquid nitrogen for DNA and protein analysis. The another one was treated with RNAlater solution in 4°C overnight for RNA analysis. Sural nerve biopsies or superficial peroneal nerve were obtained from a standard site posterior to the lateral malleolus under local anesthesia. The nerves were then fixed in 5% glutaraldehyde in 0.1 M phosphate buffer (PB) at 4 °C overnight. All samples were stored in the -80°C refrigerator for further analysis.
• Genomics, transcriptome, and proteomics
The DNA, RNA, and protein of the tissues (blood, muscle, nerve and skin) were retrieved and stored in the -80°C refrigerator. The next generation sequencing (whole exon sequencing or whole genome sequencing) and RNA-seq would be performed by NGS & Microarray Core lab in National Taiwan University or another professional team. The protein analysis would be performed by the Proteomics & Protein Function Core Lab in National Taiwan University.
• Laboratory of blood chemical substances, metals and endocrine profiles
The methods of the measurement will follow the standards set by Department of Laboratory Medicine of National Taiwan University Hospital.
• Contact heat evoked potentials
A contact heat evoked potential stimulator (Medoc, Ramat Yishai, Israel) will be used for delivering heat stimulation. Stimuli will be delivered repeatedly to the same stimulation site and the inter-stimulus interval will be randomly set to around 18~22 s. CHEP will be recorded using a Nicolet Bravo evoked potential system (Nicolet Biomedical, Madison, WI). The recording electrode was placed at the Cz and P3 of international 10-20 system. The impendence of all recording electrodes was kept below 3 kO. The evoked potentials were filtered with a bandpass filter at 0.1~30 Hz. Recording was triggered by the onset of each stimulus, and the sweep time was 1500 ms.
• Nerve excitability study
Nerve excitability studies will be undertaken on the median, tibial, peroneal and sural nerves as per previously detailed protocols. Skin temperature will be monitored at the site of stimulation and was maintained at >32°C. Stimulation and recording will be controlled by automated computerized system (QTRAC; Institute of Neurology, London, U.K.) and the stimulus current will be administered using an isolated linear bipolar constant-current stimulator (DS5; Digitimer, Welwyn Garden City, U.K.). Responses will be amplified (ICP511 AC amplifier, Grass Technologies, West Warwick, USA) with electronic noise removed (Hum Bug 50/60 Hz Noise Eliminator, Quest Scientific Instruments, North Vancouver, Canada).
• Transcranial magnetic stimulation (TMS)
In simple rTMS protocols, individual stimuli are spaced apart by identical interstimulus intervals (ISI). The stimulation protocol was in accordance with published safety recommendations. The patterned rTMS protocols included (1) Theta burst stimulation, (2) Repetitive paired-pulse TMS. All the above stimulation protocols or paradigms will follow the international guideline of the use of TMS in clinical practice and research (Rossi et al., 2009; Fitzgerald and Daskalakis, 2012; Groppa et al., 2012; Steeves et al., 2012).
• fMRI acquisition and image analysis
fMRI will be performed on a 3-T MR machine (Trio; Siemens, Erlangen, Germany). Each subject's head will be positioned comfortably inside a receive-only 8-channel birdcage head coil, supplied with ear plugs, heavily padded and secured with a strap across the forehead in order to minimize head motion. All data will be processed using SPM2 (Wellcome Department of Cognitive Neurology, London UK) 36 implemented on MATLAB (Mathworks Inc. Sherborn, MA).

Locations

Country	Name	City	State
Taiwan	National Taiwan Univeristy Hospital	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
National Taiwan University Hospital

Country where clinical trial is conducted

Taiwan, 

References & Publications (38)

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* Note: There are 38 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Lean muscle volume and fat fraction in MRI	Change from Baseline to serial follow-up MRI with the interval of 2 years.	up to 10 years
Primary	Muscle thickness and echogenecity in ultrasound	Change from Baseline to serial follow-up ultrasound with the interval of 2 years.	up to 10 years
Secondary	Natural History	To delineate the natural history of different neuromuscular disorders.	up to 10 years
Secondary	Separate disease functional score	Separate disease functional scores were: (1) Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) in ALS. The values are 0-48. A lower score indicates a worse outcome. (2) Neuropathy Impairment Score (NIS) and Nerve Disability Score (NDS) in polyneuropathy. The values are 0-244 in NIS and 0-172 in NDS. A higher score indicates a worse outcome in both scores. (3) Medical Research Council Sum-Score (MRC-SS) in myopathy. The values are 0-60. A lower score indicates a worse outcome. (4) MG Activities of Daily Living (MG-ADL) and the Quantitative Myasthenia Gravis (QMG) Test in myasthenia gravis. The values are 0-24 in MG-ADL and 0-72 in QMG. A higher score indicates a worse outcome in both scores.	up to 10 years