Muscle Strain in Multiple Sclerosis Patients Measured by Ultrasound Speckle Tracking Technique

NCT03847545 | Completed DMC

• 1 other identifier: mariathorning
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

The primary study, as outlined in the original trial registration, aiming to use ultrasound speckle tracking (STU) to monitor muscle contractility in multiple sclerosis (MS) patients receiving vs. not receiving fampridine, as well as to relate these results to performance-based measures and biomarkers to explore disease progression and muscle activity, has been cancelled. Instead four exploratory studies that originate from the initial trial registration but with revised aims, outcome measures and time points, have been prepared - see the DEVIATIONS TO TRIAL PROTOCOL included in the Statistical Analysis Plan filed under "Document section". Summary of original trial registration: Despite effective treatments, the majority of patients with multiple sclerosis experience walking impairments to a degree where walking aids or a wheelchair is required. Since 2009, medical treatment of walking impairments has been possible with fampridine, which has proven effective in approximately 40% of the patients. At present, the treatment is offered on the basis of a measurable improved walking function evaluated by simple performance-based walking tests. The treatment is offered on the basis of a measurable improved walking distance. This is shown today using simple performance-based walking tests that are difficult to complete for those MS patients who are without gait function but could still benefit from fampridine treatment. Ultrasound speckle tracking is a non-invasive ultrasound technique, with the potential to measure muscle function, including muscle contractility (through strain). Ultrasound speckle tracking is designed for dynamic cardiac muscular examination, but can in a modified version be used for assessment of the skeletal muscles. The purpose of this project is to use ultrasound speckle tracking to monitor muscle contractility in MS patients receiving vs. not receiving fampridine treatment. Furthermore, to relate these results to biomarkers in blood and urine to examine disease progression and muscle activity.

Conditions

Multiple Sclerosis

Keywords

Speckle tracking ultrasonography; Muscle strain; Fampridine; Multiple Sclerosis; Neurological diseases; Biomarkers; muscle contractility

Outcome Measures

Primary Outcomes (1)

• Gait Profile Score (GPS) - (subgroup of 30 allocated to 3D gait analysis)

  Change in GPS. GPS is a summary measure of kinematic data. The GPS evaluates the overall quality of gait by comparing nine kinematic variables, described as Gait Variable Scores (GVS), relative to normative data. GPS is the root mean square (RMS) difference between the data of relevant kinematic variables of an individual patient and the averaged data from a reference group comprised of people without gait impairments. Originally we had registred that we would use the Gait Deviation Index (GDI). GDI is a unitless value from 0 to 100. It is based upon kinematic data and is an overall quantitative index that summarises the overall gait pathology into a single score for each patient by comparison with non-pathological gait. The GDI and GPS is highly correlated. We chose to use the GPS due to the inclusion of the GVS.

  Baseline, 14 days (Change from baseline to 14 days follow-up)

Secondary Outcomes (10)

• Gait Variable Scores (GVS) - (subgroup of 30 allocated to 3D gait analysis)

  Baseline, 14 days (Change from baseline to 14 days follow-up)

• Functional test - 6 Spot Step Test (SSST)

  Baseline, 14 days (Change from baseline to 14 days follow-up)

• Functional test - Timed 25 Footwalk (T25-FW)

  Baseline, 14 days (Change from baseline to 14 days follow-up)

• Functional test - 2-minute Walk Test (2MWT)

  Baseline, 14 days (Change from baseline to 14 days follow-up)

• Walking speed - (subgroup of 30 allocated to 3D gait analysis)

  Baseline, 14 days (Change from baseline to 14 days follow-up)

Other Outcomes (31)

• Neurological examination - Expanded Disability Status Scale (EDSS)

  Baseline, 14 days (Change from baseline to 14 days follow-up)

• Neurological examination - Multiple Sclerosis Impairment Scale (MSIS)

  Baseline, 14 days (Change from baseline to 14 days follow-up)

• Functional test - Nine Hole Peg Test (9HPT)

  Baseline, 14 days (Change from baseline to 14 days follow-up)

Study Arms (1)

Intervention

EXPERIMENTAL

The participants receive Fampridine treatment (10 mg x 2 daily) for 14 days. They are testet prior to treatment and following the 14 days of treatment.

Drug: Fampridine

Interventions

Fampridine DRUG

sustained-release tablet 10 mg morning and evening.

Intervention

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Fills the criteria for fampridine treatment
• Fills the diagnostic McDonald criteria for MS
• Age between 18 and 100 years
• EDSS between 4 and 7

You may not qualify if:

• Diagnosed epilepsy
• MS attack or an acute decrease of functional capacity within the last 60 days
• Change in immunomodulatory treatment within the last 60 days
• Cancer within the last 5 years
• Clinically significant systemic disease
• Concurrent treatment with cimetidine, carvediol, propanolol and metformine

Sponsors & Collaborators

• University of Southern Denmark: lead
• Odense University Hospital: collaborator
• Sygehus Lillebaelt: collaborator
• Region of Southern Denmark: collaborator
• The Augustinus Foundation, Denmark.: collaborator
• Lounkær Fonden: collaborator
• Fonden for scleroseramte på Fyn: collaborator
• The Danish Multiple Sclerosis Society: collaborator
• TH MAIGAARDS EFTF. FRU LILY BENTHINE LUNDS FOND AF 1. JUNI 1978: collaborator
• Fonden til Lægevidenskabens Fremme: collaborator
• Overlægeråds forskningsfond: collaborator

Study Sites (1)

University of Southern Denmark - Odense Univarsity Hospital

Odense C, 5000, Denmark

Location

Related Publications (10)

• Gottberg K, Einarsson U, Ytterberg C, de Pedro Cuesta J, Fredrikson S, von Koch L, Widen Holmqvist L. Health-related quality of life in a population-based sample of people with multiple sclerosis in Stockholm County. Mult Scler. 2006 Oct;12(5):605-12. doi: 10.1177/1352458505070660.

  PMID: 17086907 BACKGROUND

• Goodman AD, Brown TR, Edwards KR, Krupp LB, Schapiro RT, Cohen R, Marinucci LN, Blight AR; MSF204 Investigators. A phase 3 trial of extended release oral dalfampridine in multiple sclerosis. Ann Neurol. 2010 Oct;68(4):494-502. doi: 10.1002/ana.22240.

  PMID: 20976768 BACKGROUND

• Goodman AD, Brown TR, Krupp LB, Schapiro RT, Schwid SR, Cohen R, Marinucci LN, Blight AR; Fampridine MS-F203 Investigators. Sustained-release oral fampridine in multiple sclerosis: a randomised, double-blind, controlled trial. Lancet. 2009 Feb 28;373(9665):732-8. doi: 10.1016/S0140-6736(09)60442-6.

  PMID: 19249634 BACKGROUND

• Solari A, Uitdehaag B, Giuliani G, Pucci E, Taus C. Aminopyridines for symptomatic treatment in multiple sclerosis. Cochrane Database Syst Rev. 2001;2002(4):CD001330. doi: 10.1002/14651858.CD001330.

  PMID: 11687106 BACKGROUND

• Jensen H, Ravnborg M, Mamoei S, Dalgas U, Stenager E. Changes in cognition, arm function and lower body function after slow-release Fampridine treatment. Mult Scler. 2014 Dec;20(14):1872-80. doi: 10.1177/1352458514533844. Epub 2014 May 22.

  PMID: 24852920 BACKGROUND

• Jensen HB, Mamoei S, Ravnborg M, Dalgas U, Stenager E. Distribution-based estimates of minimum clinically important difference in cognition, arm function and lower body function after slow release-fampridine treatment of patients with multiple sclerosis. Mult Scler Relat Disord. 2016 May;7:58-60. doi: 10.1016/j.msard.2016.03.007. Epub 2016 Mar 18.

  PMID: 27237758 BACKGROUND

• Jensen HB, Ravnborg M, Dalgas U, Stenager E. 4-Aminopyridine for symptomatic treatment of multiple sclerosis: a systematic review. Ther Adv Neurol Disord. 2014 Mar;7(2):97-113. doi: 10.1177/1756285613512712.

  PMID: 24587826 BACKGROUND

• Mondillo S, Galderisi M, Mele D, Cameli M, Lomoriello VS, Zaca V, Ballo P, D'Andrea A, Muraru D, Losi M, Agricola E, D'Errico A, Buralli S, Sciomer S, Nistri S, Badano L; Echocardiography Study Group Of The Italian Society Of Cardiology (Rome, Italy). Speckle-tracking echocardiography: a new technique for assessing myocardial function. J Ultrasound Med. 2011 Jan;30(1):71-83. doi: 10.7863/jum.2011.30.1.71.

  PMID: 21193707 BACKGROUND

• Frich, L.H., et al., Direct isometric muscle strain analyses using speckle tracking technology. A validation study, in European Muscle Conference 2017. 2017, Journal of Muscle Research and Cell Motility: Potsdam

  BACKGROUND

• Thorning M, Nielsen HH, Frich LH, Jensen HB, Lambertsen KL, Holsgaard-Larsen A. Gait quality and function after fampridine treatment in patients with multiple sclerosis - A prospective cohort study. Clin Biomech (Bristol). 2022 Dec;100:105826. doi: 10.1016/j.clinbiomech.2022.105826. Epub 2022 Nov 17.

  PMID: 36436320 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis; Sprains and Strains

Interventions

4-Aminopyridine

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Aminopyridines; Amines; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Helle H. Nielsen, MD, PhD

  Department of Neurology, Odense University Hospital, Odense, Denmark

  STUDY DIRECTOR

• Maria Thorning, MSc

  Department of Neurology, Odense University Hospital, Odense, Denmark

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective cohort Study

Study Record Dates

• First Submitted: December 19, 2018
• First Posted: February 20, 2019
• Study Start: December 12, 2018
• Primary Completion: October 15, 2021
• Study Completion: October 15, 2021
• Last Updated: April 5, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data will become availerble six months after submission. Time period of five years.
• Access Criteria: All data are hosted at OPEN (Odense Patient Explorative Network), which allows data sharing upon request.

Locations

DK (1)