Ultrasonography of the Neuromuscular Degeneration Behavior in Amyotrophic Lateral Sclerosis

Amyotrophic Lateral Sclerosis Clinical Trial

Official title:

Ultrasonography of the Neuromuscular Degeneration Behavior in ALS: a Longitudinal Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03683875
• Other study ID #: ECO-ELA
• Status: Completed
• Start date: October 1, 2018
• Est. completion date: March 10, 2020

Study information

• Verified date: October 2021
• Source: Hospital General Universitario Santa Lucia
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Amyotrophic Lateral Sclerosis (ALS) is a progressive and fatal neurological disease.

An exhaustive and frequent clinical evaluation can lead to establish an adequate and early treatment of the consequences of its evolution.

Objectives.

1. To evaluate the evolution of diaphragmatic and peripheral neuromuscular degeneration by ultrasound examination in patients with ALS and to establish possible evolution patterns.

2. To verify the relationship between the degenerative peripheral and diaphragmatic neuromuscular changes evaluated by ultrasonography and changes in clinical scales frequently used.

3. To compare the ultrasonographic features of subjects with ALS and a sample of healthy subjects Methods. A longitudinal observational study in a consecutive sample of patients diagnosed with ALS will be realized. All the patients will be examined 3 times, with an interval of at least 3 months between tests. Bilateral and cross sectional ultrasonography of several peripheral muscles and diaphragm will be performed at rest and during muscle contraction. All the images will be processed and analyzed for obtaining morphometric variables (muscle thickness) and textural ones (echogenic variation, entropy, homogeneity, textural contrast and correlation). Frequency of twitches will be also recorded in peripheral muscles.Also clinical features will be noted, every time of the 3 exams, from Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-r), British Medical Council Research Scale(MRC), and routine pulmonary tests.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: March 10, 2020
• Est. primary completion date: October 1, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Definite ALS

Exclusion Criteria:

• Primary Lateral Sclerosis (PLS)

• Other forms of motor neuron disorders

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

Locations

Country	Name	City	State
Spain	Hospital General Universitario Santa Lucia	Cartagena	Murcia

Sponsors (2)

Lead Sponsor	Collaborator
Hospital General Universitario Santa Lucia	Universidad de Murcia

Country where clinical trial is conducted

Spain, 

References & Publications (13)

Arts IM, Overeem S, Pillen S, Kleine BU, Boekestein WA, Zwarts MJ, Jurgen Schelhaas H. Muscle ultrasonography: a diagnostic tool for amyotrophic lateral sclerosis. Clin Neurophysiol. 2012 Aug;123(8):1662-7. doi: 10.1016/j.clinph.2011.11.262. Epub 2012 Jan 13. — View Citation

Arts IM, Overeem S, Pillen S, Schelhaas HJ, Zwarts MJ. Muscle ultrasonography to predict survival in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 2011 May;82(5):552-4. doi: 10.1136/jnnp.2009.200519. Epub 2010 Apr 14. — View Citation

Arts IM, Pillen S, Schelhaas HJ, Overeem S, Zwarts MJ. Normal values for quantitative muscle ultrasonography in adults. Muscle Nerve. 2010 Jan;41(1):32-41. doi: 10.1002/mus.21458. — View Citation

Arts IM, van Rooij FG, Overeem S, Pillen S, Janssen HM, Schelhaas HJ, Zwarts MJ. Quantitative muscle ultrasonography in amyotrophic lateral sclerosis. Ultrasound Med Biol. 2008 Mar;34(3):354-61. Epub 2007 Oct 26. — View Citation

Arts IMP, Overeem S, Pillen S, Jurgen Schelhaas H, Zwarts MJ. Muscle changes in amyotrophic lateral sclerosis: a longitudinal ultrasonography study. Clin Neurophysiol. 2011 Mar;122(3):623-628. doi: 10.1016/j.clinph.2010.07.023. — View Citation

Cartwright MS, Walker FO, Griffin LP, Caress JB. Peripheral nerve and muscle ultrasound in amyotrophic lateral sclerosis. Muscle Nerve. 2011 Sep;44(3):346-51. doi: 10.1002/mus.22035. Epub 2011 Aug 3. — View Citation

Fantini R, Mandrioli J, Zona S, Antenora F, Iattoni A, Monelli M, Fini N, Tonelli R, Clini E, Marchioni A. Ultrasound assessment of diaphragmatic function in patients with amyotrophic lateral sclerosis. Respirology. 2016 Jul;21(5):932-8. doi: 10.1111/resp.12759. Epub 2016 Mar 19. — View Citation

Hiwatani Y, Sakata M, Miwa H. Ultrasonography of the diaphragm in amyotrophic lateral sclerosis: clinical significance in assessment of respiratory functions. Amyotroph Lateral Scler Frontotemporal Degener. 2013 Mar;14(2):127-31. doi: 10.3109/17482968.2012.729595. Epub 2012 Oct 30. — View Citation

Martínez-Payá JJ, Del Baño-Aledo ME, Ríos-Díaz J, Tembl-Ferrairó JI, Vázquez-Costa JF, Medina-Mirapeix F. Muscular Echovariation: A New Biomarker in Amyotrophic Lateral Sclerosis. Ultrasound Med Biol. 2017 Jun;43(6):1153-1162. doi: 10.1016/j.ultrasmedbio.2017.02.002. Epub 2017 Apr 8. — View Citation

Martínez-Payá JJ, Ríos-Díaz J, Del Baño-Aledo ME, Tembl-Ferrairó JI, Vazquez-Costa JF, Medina-Mirapeix F. Quantitative Muscle Ultrasonography Using Textural Analysis in Amyotrophic Lateral Sclerosis. Ultrason Imaging. 2017 Nov;39(6):357-368. doi: 10.1177/0161734617711370. Epub 2017 May 28. — View Citation

Mayans D, Cartwright MS, Walker FO. Neuromuscular ultrasonography: quantifying muscle and nerve measurements. Phys Med Rehabil Clin N Am. 2012 Feb;23(1):133-48, xii. doi: 10.1016/j.pmr.2011.11.009. Epub 2011 Dec 9. Review. — View Citation

Pinto S, Alves P, Pimentel B, Swash M, de Carvalho M. Ultrasound for assessment of diaphragm in ALS. Clin Neurophysiol. 2016 Jan;127(1):892-897. doi: 10.1016/j.clinph.2015.03.024. Epub 2015 Apr 25. — View Citation

Schreiber S, Abdulla S, Debska-Vielhaber G, Machts J, Dannhardt-Stieger V, Feistner H, Oldag A, Goertler M, Petri S, Kollewe K, Kropf S, Schreiber F, Heinze HJ, Dengler R, Nestor PJ, Vielhaber S. Peripheral nerve ultrasound in amyotrophic lateral sclerosis phenotypes. Muscle Nerve. 2015 May;51(5):669-75. doi: 10.1002/mus.24431. Epub 2015 Mar 14. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Measuring thickness of peripheral muscles using an ultrasound device	These measurements will be carried out in the biceps brachialis, forearm flexors, thenar eminence muscle, quadriceps and tibialis anterior which will be compared between patient with ALS and control group.	3 months
Primary	Measuring echointensity of peripheral muscles using an ultrasound device	These measurements will be carried out in the biceps brachialis, forearm flexors, thenar eminence muscle, quadriceps and tibialis anterior which will be compared between patient with ALS and control group.	3 months
Primary	Measuring sonoelastography of peripheral muscles using an ultrasound device	These measurements will be carried out in the biceps brachialis, forearm flexors, thenar eminence muscle, quadriceps and tibialis anterior which will be compared between patient with ALS and control group.	3 months
Primary	Thickness Fraction of the Diaphragm in ALS patients and control group.	It is calculated as the difference between thickness at end inspiration and end expiration	3 months
Primary	Diaphragmatic Excursion (quiet and forced) of the Diaphragm in ALS patients and control group	Displacement of the right diaphragm dome	3 months
Secondary	Measurement of muscle fasciculations using an ultrasound device	Each peripheral muscle will be screened during 30 seconds	3 months
Secondary	Measurement of muscle strength using Medical Research Council Scale (MRCs)	Graded on the medical research council scale. This scale grades muscle power on a scale of 0 to 5: Grade 0: no movement is observed Grade 1: only a trace or flicker of movement is seen or flet in the muscle. or fasciculation is observed Grade 2: movement is possible only if the resistance of gravity is removed Grade 3: movement against gravity is possible but not against resistance of the examiner Grade 4: muscle stregth is reduced but muscle contraction can move joint against gravity and resistance Grade 5: muscle contracts normally against full resistance	3 months
Secondary	Measurement Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-r)	Questionnaire with 12 items with a score from 0 to 4 each item: Speech; Salivation; Swallowing; Handwriting 5a. Cutting food and handling utensils (patients without gastrostomy) 5b. Cutting food and handling utensils(scale for patients with gastrostomy); 6. Dressing and hygiene 7. Turning in bed and adjusting bed clothes 8. Walking 9. Climbing stairs 10. Dyspnea 11. Orthopnea 12. Respiratory insufficiency; There are three main pathways of progression, the questions are also divided in relation to the types of onset. Questions 1 to 3 are related to bulbar onset, questions 4 to 9 are related to limb onset and questions 10-12 are related to respiratory onset. The Scale goes from 0 to 48, more points meaning better situation.	3 months
Secondary	Measuring Forced Vital Capacity	This volume expressed in liters will be measured in supine and seated positions.	3 months
Secondary	Maximal Inspiratory Pressure (MIP)	Measure of the strength of inspiratory muscles expressed in centimeters of water, is the highest mouth pressure sustained for 1 s during a maximum inspiratory effort	3 months
Secondary	Sniff- nasal inspiratory pressure (SNIP)	It consists of measuring nasal pressure in an occluded nostril during a maximal sniff performed through the contralateral nostril, expressed in centimeters of water	3 months
Secondary	Peak Cough Flow (PCF)	Maximal peak cough flow expressed in liters per minute	3 months
Secondary	Partial Pressure of Carbon Dioxide in Arterial Blood (PaCO2)	Obtained by a radial arterial blood sample and expressed in millimeters of mercury	3 months
Secondary	Cumulative time percentage with SpO2 under 90% (CT90)	SpO2 is an estimate of arterial oxygen saturation expressed in percentage under 90% obtained from a nocturnal oximetry	3 months