Study of Lisdexamfetamine Sulfate to Treat Cognitive Dysfunction in Multiple Sclerosis
Condition: Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Sclerosis
Intervention: lisdexamfetamine sulfate; placebo
Intervention description: 30mg lisdexamfetamine OD, increased to 70mg OD over 4 weeks and continued on 70mg OD for 4 weeks; sugar pill
Intervention MeSH terms: Lisdexamfetamine Dimesylate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 63.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: No

Summary:

      Amphetamines have been shown to improve cognition but its use is limited due to its side
      effects. Lisdexamfetamine is an amphetamine pro-drug, minimizing these effects and has been
      safely used in children and adults with Attention Deficit Hyperactivity Disorder (ADHD). The
      investigators hypothesize that lisdexamfetamine may improve cognitive abilities in MS
      patients with documented cognitive dysfunction. Because lisdexamfetamine is a stimulant its
      positive effects should be observed primarily in the domains of processing speed and working
      memory. The investigators therefore propose a study in which the primary objective will be to
      assess the efficacy of lisdexamfetamine in improving attention and processing speed in MS.
      The secondary objectives will be (a) the assessment of the safety and tolerability of
      lisdexamfetamine in the MS population, and (b) to test for effects of the drug on other
      cognitive domains, depression, and self and informant reports of cognitive and executive
      function demanding activities and behaviors.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Males/Females who are ≥ 18 years old and < 55 years old and are capable of
             understanding and complying with the protocol, including speaking and writing fluent
             English and having at least a 9th grade education.

          -  Have a diagnosis of either Relapsing Remitting or Secondary Progressive MS, as per
             revised McDonald's Criteria (68).

          -  Have not received steroids in last thirty (30) days or a relapse in the last ninety
             (90) days, and whose MS is considered stable.

          -  Presence of cognitive dysfunction characterized by slowed processing speed as
             indicated by a score of -1.5 SD below age/education matched norms on the SDMT or the
             PASAT.

          -  An Expanded Disability Status Scale (EDSS) of ≤ 6.5

          -  Have given written informed consent prior to any study-related procedure not part of
             normal medical care, with the understanding that consent may be withdrawn by the
             subject at any time without prejudice to his/her future medical care.

          -  Are capable of performing the requirements of a NP test battery including at least
             20/70 near visual acuity by near vision chart, with correction allowed.

          -  If female, must neither be pregnant nor breast-feeding and must either (a) be > 12
             months post-menopausal or surgically sterilized, or (b) agree to use an acceptable
             method of birth control for the duration of the study. Abstinence will not be
             considered an acceptable method of birth control.

        Exclusion Criteria:

          -  Have cognitive deficits caused by concomitant medication usage or other significant
             neurological/psychological disease e.g. Alzheimer's disease, Parkinson's disease,
             stroke, transient ischemic attack, Vascular Dementia, Huntington's disease, traumatic
             brain injury or chronic CNS infection

          -  Have evidence of other medical cause(s) of cognitive impairment

          -  Have evidence of major depression as determined by a positive BDIFS and clinician
             interview

          -  Have uncontrolled or labile hypertension, tachycardia, cardiovascular or
             cerebrovascular disease

          -  Have demonstrated a hypersensitivity to amphetamines in the past

          -  The following concomitant medications are not permitted to be used within 28 days of
             enrollment or during the study

               -  Monoamine Oxidase Inhibitors

               -  Inhaled Beta2-agonists

               -  Sympathomimetics

               -  Antipsychotic agents

               -  Modafinil

               -  Tricyclic Antidepressants

               -  Anticonvulsants other than gabapentin and pregabalin

          -  The following medications are permitted if the patient has been on a stable dose for ≥
             6 weeks:

               -  Short acting benzodiazepines, qhs administration only

               -  Gabapentin and pregabalin Cholinesterase inhibitors other than donepezil,
                  galantamine, and rivastigmine

               -  Memantine

               -  Anti-spasmodics

               -  Selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake
                  inhibitors.