Resistance Training and Amino Pyridine in Multiple Sclerosis (RETRAP)

RETRAP - A Double Blind, Randomized, Placebo Controlled Study of the Effect of the Combination of Resistance Training and Prolonged Release Fampridine in Patients With Multiple Sclerosis

Prolonged-release fampridine (SR-fampridine) can improving walking capacity in approximately 40% of MS patients suffering from this by overcoming partly or total conduction block due to demyelination.

Resistance training has been shown to provide the same kind of benefits for patients by targeting the muscular component of the motor unit. Thus by combining the two it is likely to see an synergistic effect.

This trial is designed as a double blind, randomized placebo controlled trial with subsequent cross-over.

Participants in the two arms will go through the same progressive training program targets at the lower limbs. For 24 weeks one group receives SR-fampridine and the other receives placebo. in the the end there is another four weeks of training after cross-over has been performed.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: Placebo; Drug: SR-fampridine

Detailed Description

See above

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Esbjerg, Denmark, 6700
    • Sydvestjysk Sygehus
  • Odense, Denmark, 5000
    • Odense University Hospital
  • Sønderborg, Denmark, 6400
    • Sygehus Sønderjylland
  • Vejle, Denmark, 7100
    • Sygehus Lillebælt

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with relapsing remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPMS) or primary progressive multiple sclerosis (PPMS) fulfilling the McDonald criteria
• Expandend Disability Status Scale (EDSS) 3-6.5
• Pyramidal Functional Score ≥ 2
• Participants must be able to transport self to gym and to the University of Southern Denmark
• Participants must be able to complete T25FW and SSST
• Fertile female participants are obliged to use hormonal contraceptive measures

Exclusion Criteria:

• History of epileptic seizures
• MS relapse or change in disease modifying treatment (DMT) within 60 days
• Cancer within five years
• Blood pressure ≥ 160/100
• Severe arrhythmia or ischaemic heart disease or unexplained abnormal cardiac auscultation
• ≥ ALT 90 U/l, ≥ BSP 210 U/l, ≥ γ-GT 230 U/l
• GFR < 80 ml/min.
• History of severe pulmonary disease or unexplained abnormal pulmonary auscultation
• Pregnancy
• Breastfeeding
• Allergy to substances contained in prolonged release Fampridine tablets
• Concomitant treatment with carvedilol, propranolol or metformin.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SR-fampridine/placebo; 24 weeks of SR-fampridine followed by four weeks of inactive placebo.	Drug: Placebo; Drug: SR-fampridine; One arm receives SR-fampridine 10 mg BID for 24 weeks followed by four weeks of inactive placebo BID. The other arm receives placebo BID for 24 weeks followed by four weeks of SR-fampridine 10 mg BID for four weeks.; Other Names: Fampyra
Experimental: Placebo/SR-fampridine; 24 weeks of inactive placebo followed by four weeks of SR-fampridine	Drug: Placebo; Drug: SR-fampridine; One arm receives SR-fampridine 10 mg BID for 24 weeks followed by four weeks of inactive placebo BID. The other arm receives placebo BID for 24 weeks followed by four weeks of SR-fampridine 10 mg BID for four weeks.; Other Names: Fampyra

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Muscle power in the lower limbs	Muscle power in the lower limbs is measured by dynamometry pre and post resistance training	Muscle power will be measured after 14 weeks of resistance training.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Activity	Activity measured by accelerometry.	Accelerometry is measured after 14 weeks of resistance training
Walking capacity	Walking capacity measured by the Six Spot Step Test (SSST)	Walking capacity is measured after 26 weeks of resistance training
Walking speed	Walking speed measured by the Timed 25 Foot Walk (T25FW) and the 6-Minute Walking Test (6MWT)	Walking speed is measured after 26 weeks of resistance training
Functional capacity in the lower limbs	Functional capacity measured by the Chair Stand Test (CST)	Funcyional capacity in the lower limbs is measured after 26 weeks of resistance training
Self rated walking capacity	Self rated walking capacity measured by the 12-Item Multiple Sclerosis Walking Scale (MSWS12)	Self rated walking capacity is measured after 26 weeks of resistance training

Collaborators and Investigators

• Sponsor: University of Southern Denmark
• Collaborators: Biogen; Region of Southern Denmark
• Investigators: Principal Investigator: Henrik B Jensen, MD, University of Southern Denmark

Publications and helpful links

General Publications

• Dalgas U, Stenager E, Jakobsen J, Petersen T, Hansen HJ, Knudsen C, Overgaard K, Ingemann-Hansen T. Resistance training improves muscle strength and functional capacity in multiple sclerosis. Neurology. 2009 Nov 3;73(18):1478-84. doi: 10.1212/WNL.0b013e3181bf98b4.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2014
• Primary Completion (Actual): January 1, 2015
• Study Completion (Actual): January 1, 2015

Study Registration Dates

• First Submitted: May 9, 2014
• First Submitted That Met QC Criteria: May 16, 2014
• First Posted (Estimate): May 20, 2014

Study Record Updates

• Last Update Posted (Actual): August 23, 2018
• Last Update Submitted That Met QC Criteria: August 22, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Potassium Channel Blockers; 4-Aminopyridine
• Other Study ID Numbers: RETRAP; 2011-002959-34 (EudraCT Number)