Clinical trial NCT01879202: Methylphenidate as Treatment Option of Fatigue in Multiple Sclerosis
Official title: Methylphenidate Modified-release as Treatment of MS-associated Fatigue. A Single-center Randomized Double-blind Placebo-controlled Study.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Multiple Sclerosis
Fatigue
Keywords: multiple sclerosis
fatigue
fatigue severity scale
fatigue impact scale
quality of life
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
First posted: 2013-06-17
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Fatigue is a common symptom in multiple sclerosis (MS) that is characterized by physical and/or mental exhaustion. Fatigue is difficult to treat and treatment efficacy of available therapy is limited. The goal of this study is to determine whether MS-associated fatigue improves after 6 weeks of methylphenidate therapy. Treatment efficacy will be measured by a questionnaire called "Fatigue Severity Scale" (FSS).

Detailed description: The management oft fatigue comprises nonpharmacologic approaches like exercise, cooling procedures, nutrition, and energy conservation programmes. These strategies should be considered as first-line options since they add to overall wellbeing, have no side effects and increase the patient's autonomy. However, in most cases these strategies will not suffice to keep the patient symptom free on the long term. Also, patients with overwhelming and severe fatigue will be unlikely to engage in exercise. In these cases adding pharmacologic therapy will be the next step. Until now, Amantadine, Modafinil, and Pemoline have been used among others, with some success. Also antidepressants like buprione, fluoxetine, and venlafaxine have been used although they have never been systematically studied for the management of MS-related fatigue. However, if a mood disorder is present, it is appropriate to treat it before pursuing pharmacologic therapy of fatigue. Nevertheless, the response rate of all pharmacologic therapies of MS-related fatigue is not totally convincing making alternative pharmacologic therapies furthermore desirable. Methylphenidate is an antagonist of dopamine and norepinephrine transporters on the presynaptic neuronal cell membrane. Reduced reuptake results in an increase in extracellular levels of both neurotransmitters. Until now, methylphenidate has been successfully used to treat fatigue in HIV and parkinson´s disease, data on its efficacy in MS are not available. The aim of this study is to determine the efficacy of methylphenidate treatment in MS-associated fatigue. The treatment phase will be 6 weeks and treatment efficacy will be measured by validated questionnaires (Fatigue Severity Scale FSS, modified Fatigue Impact Scale MFIS) and by a neuropsychological test (Test for Attentional Performance).

Eligibility criteria: Inclusion Criteria:

* Diagnosis of multiple sclerosis according to McDonalds criteria.
* Age \> 18 years
* Fatigue as measured by Fatigue Severity Scale
* Signed informed consent

Exclusion Criteria:

* Known allergy or hypersensitivity to Methylphenidate or any of its ingredients
* Marked anxiety, tension and agitation
* Patients with glaucoma or hyperthyroidism
* Patients with motor-tics, a family history or diagnosis of Tourette´s syndrome
* Treatment with monoamine oxidase inhibitors, also within a minimum of 14 days following discontinuation (hypertensive crisis may result).
* Phaeochromocytoma
* Pre-existing cardiovascular disorders including severe hypertension, angina, arterial occlusive disorder, heart failure, haemodynamically significant congenital heart disease, cardiomyopathies, myocardial infarction, potentially life-threatening arrhythmias and channelopathies.
* History of drug dependence or alcoholism
* History of seizures
* Pregnant women or females of childbearing potential who want to become pregnant within the study period.
* Severe psychiatric disorders
* Change of any medication treatment \<8 weeks before starting the study
* Participation in any other clinical trial at the same time

Primary outcomes:
measure: Change of Fatigue as measured by Fatigue Severity Scale
timeFrame: Baseline versus follow-up at 6 weeks
Secondary outcomes:
measure: Change of Fatigue as measured by Modified Fatigue Impact Scale (MFIS)
timeFrame: Baseline versus follow up at 6 weeks
Other outcomes:
measure: Change of Quality of life as assessed by Hamburger Lebensqualitätsfragebogen (HAQUAMS)
timeFrame: Baseline versus follow up at 6 weeks
measure: Fatigue as measured by TAP (Test for Attentional Performance)
timeFrame: Baseline, after 6 weeks
measure: Quality of sleep as measured by Epworth Sleepiness Scale (ESS)
timeFrame: Baseline, after 6 weeks
measure: Quality of sleep as measured by Pittsburgh Sleep Quality Index
timeFrame: Baseline, after 6 weeks
Locations:
city: Vienna
country: Austria
facility: Medical University of Vienna, Department of Neurology
Study officials:
affiliation: Medical University of Vienna, Department of Neurology
name: Fritz Leutmezer, MD
role: PRINCIPAL_INVESTIGATOR
References: