functional MRI study to evaluate improvement of hand performance after combined motor exercise and aminopiridine assumption

• Register: EUCTR
• Last refreshed on: 10 February 2014
• Main ID: EUCTR2012-000287-17-IT
• Date of registration: 18/06/2012
• Prospective Registration: No
• Primary sponsor: FONDAZIONE SANTA LUCIA
• Public title: functional MRI study to evaluate improvement of hand performance after combined motor exercise and aminopiridine assumption
• Scientific title: PROMOTION OF FUNCTIONAL RESTORATION THROUGH PHARMACOLOGICAL MODULATION OF BRAIN PLASTICITY WITH AMINOPYRIDINE IN PATIENTS WITH MULTIPLE SCLEROSIS STUDIED BY FUNCTIONAL MRI
• Date of first enrolment: 21/05/2012
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-000287-17
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: yes Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: yes Other specify the comparator: presence or absence of physical exercise Number of treatment arms in the trial: 4

Countries of recruitment

Italy

Contacts

• Name: DIREZIONE SCIENTIFICA
• Affiliation: FONDAZIONE SANTA LUCIA

• Name: DIREZIONE SCIENTIFICA
• Affiliation: FONDAZIONE SANTA LUCIA

Key inclusion & exclusion criteria

Inclusion criteria:
Right handed Multiple Sclerosis patients without relapses in the previous year and, if under pharmacological treatment, with a stable dose regimen for at least 3 months. Patients will be included if they present with a right hand dexterity impairment (average of 2 performances in 9-hole peg test: >30 seconds).
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Rehab in the previous 6 months; significant cognitive deficit that may prevent engagement in the study; contraindications to MRI scan; allergy to the drug or the eccipients; any relevant pathology that contraindicate drug intake.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Patients with MS, without relevant medical conditions, with right upper limb impairment assessed by a hand dexterity test will be included.Patients will be in a non-active phase of the disease and under a stable pharmacological treatment.They will not be included if they have received physiotherapy in the previous few months. Healthy volunteers will be recruited if they have no relevant medical condition and no contraindication to perform a MRI scan.
MedDRA version: 14.1 Level: LLT Classification code 10028053 Term: MS System Organ Class: 10029205 - Nervous system disorders

Intervention(s)

Trade Name: FAMPYRA
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: FAMPRIDINE
CAS Number: 504-24-5
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Prolonged-release tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: 1. To investigate the brain correlates of rehabilitation (rehab)-related clinical benefits on upper limb function in Multiple Sclerosis (MS) and to qualify imaging markers associated with performance improvements. Patterns of movement control can be adaptively driven by rehab through re-learning of lost function. Rehab-mediated improvements may be associated with brain functional changes in sensorimotor regions that can be measured with neuroimaging methods.

2. To enhance rehab-mediated functional recovery in MS by pharmacological modulation of brain plasticity. Pharmacological modulation of brain plasticity aims to predispose sensorimotor systems to rehab effects, improving and prolonging rehab effect in MS. The association of a drug to physical intervention will test this hypothesis.

Primary end point(s): 1. To establish the clinical benefit of rehab on right upper limb function and to identify imaging markers of clinical improvements. Rehab clinical benefits will be assessed using 9-hole peg test. MRI markers of clinical improvements will be identified through correlations between functional changes in patterns of brain activations and performance improvements.
2. To establish the additional clinical benefit of the association of rehab with drug. This benefit will be tested in terms of (a) difference in clinical improvements between the group treated with rehab plus placebo and the group treated with rehab plus drug; (b) prolongation of rehab benefit measured as difference in performance changes during the follow-up with cessation of intervention.

Timepoint(s) of evaluation of this end point: Primary end-points will be evaluated 6 weeks after the beginning of rehab and drug or placebo intake. At the end of the intervention period, patients will be evaluated after 6 weeks to test for prolongation of rehab benefit in the group treated with active drug.

Secondary Objective: To test the indirect benefits of rehab alone and in associated with pharmacological treatment. For this purpose, clinical scales assessing cognitive functions, mood, anxiety and quality of life will be assessed. In the sub-study, the objective will be the characterisation and quantification of changes in brain activity induced by rehab alone and in association with pharmacological treatment.

Secondary Outcome(s)

Secondary end point(s): Indirect clinical benefit of rehab in association with drug. This additional benefit will be assessed using quality of life (MSQoL-54), and mood and anxiety (Beck Depression Inventory Scale and STAI) tests.
In those patients who will participate in the electrophysiological sub-study, changes in cortical activity resulting from association of rehab with drug will be tested.

Timepoint(s) of evaluation of this end point: Secondary end-points will be evaluated 6 weeks after starting rehab and drug intake. Patients will be also evaluated 6 weeks after rehab and drug intake cessation.

Secondary ID(s)

RC12-01

Source(s) of Monetary Support

Ministero della Salute