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Study of Lisdexamfetamine Sulfate to Treat Cognitive Dysfunction in Multiple Sclerosis

Primary Purpose

Multiple Sclerosis

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
lisdexamfetamine sulfate
placebo
Sponsored by
State University of New York at Buffalo
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Sclerosis

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

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prior to any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to his/her future medical care.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.

Sites / Locations

  • Kaleida Health, Jacobs Neurological Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

lisdexamfetamine sulfate

Sugar pill

Arm Description

30mg lisdexamfetamine OD, increased to 70mg OD over 4 weeks and continued on 70mg OD for 4 weeks

Placebo will be administered in the same fashion as the treatment arm

Outcomes

Primary Outcome Measures

Symbol Digit Modalities Test (SDMT)
The Symbol Digit Modalities Test (SDMT) presents a series of nine symbols, each paired with a single digit in a key at the top of a stimulus page. Subjects voice the number associated with each symbol as rapidly as possible. The examiner records the total amount of responses completed. The task continues for 90 seconds with the research staff recording responses. The SDMT score ranges from 0 to 110, with higher values representing a better outcome in cognitive processing speed.
Paced Auditory Serial Audition Test (PASAT)
The PASAT is a test requiring attention and vigilance. In this test, the patient listens to a tape recording of digits presented one at a time. The task for the patient is to add each number to the one immediately preceding it. For example, the recording might present the numbers 1, 7, 5, 4. The patient adds the first two numbers (1 + 7) and responds with the number 8. The patient then adds the second two numbers (7 + 5) and responds with the number 12. The patient then adds the third two numbers (5 + 4) and responds with the number 9. This continues for a total of 61 numbers presented in a random order. The patients score is the total number correct out of 60 (Stebbins et al. 2007). The PASAT score ranges from 0 to 60, with higher values representing a better outcome in cognitive processing speed.

Secondary Outcome Measures

California Verbal Learning Test - 2nd Edition
The California Verbal Learning Test Second Edition (CVLT2) begins with the examiner reading a list of 16 words. Patients listen to the list and report as many of the items as possible. After recall is recorded, the entire list is read again. Altogether, there are five learning trials, the total correct of all trials is summed together creating a total verbal learning score. The CVLT-II total verbal learning score ranges from 0 to 80, with higher values representing a better outcome in verbal learning/memory.
Brief Visuospatial Memory Test - Revised
The Brief Visuospatial Memory Test Revised (BVMTR) presents six abstract designs for 10 seconds. The display is removed from view and patients render the stimuli via pencil on paper manual responses. There are three learning trials in which patients attempt to replicate the stimuli previously presented. Patients are given a score for all three trials based on correct location and accuracy of the replicated stimuli. Each trial can be awarded up to 12 points, the sum of total points awarded across all three trials is the total learning score. The BVMT-R total learning score ranges from 0 to 36, with higher values representing a better outcome in visuospatial learning/memory.
Vitals
Heart rate
Vitals (Diastolic Blood Pressure)
diastolic blood pressure
Vitals (Systolic Blood Pressure)
systolic blood pressure

Full Information

First Posted
March 23, 2011
Last Updated
August 23, 2022
Sponsor
State University of New York at Buffalo
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1. Study Identification

Unique Protocol Identification Number
NCT01615887
Brief Title
Study of Lisdexamfetamine Sulfate to Treat Cognitive Dysfunction in Multiple Sclerosis
Official Title
Effects of Lisdexamfetamine on Bradyphrenia in Multiple Sclerosis
Study Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Completed
Study Start Date
November 2009 (undefined)
Primary Completion Date
August 2011 (Actual)
Study Completion Date
August 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
State University of New York at Buffalo

4. Oversight

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
63 (Actual)

8. Arms, Groups, and Interventions

Arm Title
lisdexamfetamine sulfate
Arm Type
Experimental
Arm Description
30mg lisdexamfetamine OD, increased to 70mg OD over 4 weeks and continued on 70mg OD for 4 weeks
Arm Title
Sugar pill
Arm Type
Placebo Comparator
Arm Description
Placebo will be administered in the same fashion as the treatment arm
Intervention Type
Drug
Intervention Name(s)
lisdexamfetamine sulfate
Other Intervention Name(s)
Vyvanse
Intervention Description
30mg lisdexamfetamine OD, increased to 70mg OD over 4 weeks and continued on 70mg OD for 4 weeks
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
sugar pill
Primary Outcome Measure Information:
Title
Symbol Digit Modalities Test (SDMT)
Description
The Symbol Digit Modalities Test (SDMT) presents a series of nine symbols, each paired with a single digit in a key at the top of a stimulus page. Subjects voice the number associated with each symbol as rapidly as possible. The examiner records the total amount of responses completed. The task continues for 90 seconds with the research staff recording responses. The SDMT score ranges from 0 to 110, with higher values representing a better outcome in cognitive processing speed.
Time Frame
8 weeks
Title
Paced Auditory Serial Audition Test (PASAT)
Description
The PASAT is a test requiring attention and vigilance. In this test, the patient listens to a tape recording of digits presented one at a time. The task for the patient is to add each number to the one immediately preceding it. For example, the recording might present the numbers 1, 7, 5, 4. The patient adds the first two numbers (1 + 7) and responds with the number 8. The patient then adds the second two numbers (7 + 5) and responds with the number 12. The patient then adds the third two numbers (5 + 4) and responds with the number 9. This continues for a total of 61 numbers presented in a random order. The patients score is the total number correct out of 60 (Stebbins et al. 2007). The PASAT score ranges from 0 to 60, with higher values representing a better outcome in cognitive processing speed.
Time Frame
8 Weeks
Secondary Outcome Measure Information:
Title
California Verbal Learning Test - 2nd Edition
Description
The California Verbal Learning Test Second Edition (CVLT2) begins with the examiner reading a list of 16 words. Patients listen to the list and report as many of the items as possible. After recall is recorded, the entire list is read again. Altogether, there are five learning trials, the total correct of all trials is summed together creating a total verbal learning score. The CVLT-II total verbal learning score ranges from 0 to 80, with higher values representing a better outcome in verbal learning/memory.
Time Frame
8 weeks
Title
Brief Visuospatial Memory Test - Revised
Description
The Brief Visuospatial Memory Test Revised (BVMTR) presents six abstract designs for 10 seconds. The display is removed from view and patients render the stimuli via pencil on paper manual responses. There are three learning trials in which patients attempt to replicate the stimuli previously presented. Patients are given a score for all three trials based on correct location and accuracy of the replicated stimuli. Each trial can be awarded up to 12 points, the sum of total points awarded across all three trials is the total learning score. The BVMT-R total learning score ranges from 0 to 36, with higher values representing a better outcome in visuospatial learning/memory.
Time Frame
8 weeks
Title
Vitals
Description
Heart rate
Time Frame
8 weeks
Title
Vitals (Diastolic Blood Pressure)
Description
diastolic blood pressure
Time Frame
8 weeks
Title
Vitals (Systolic Blood Pressure)
Description
systolic blood pressure
Time Frame
8 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
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.
Facility Information:
Facility Name
Kaleida Health, Jacobs Neurological Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14203
Country
United States

12. IPD Sharing Statement

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Study of Lisdexamfetamine Sulfate to Treat Cognitive Dysfunction in Multiple Sclerosis

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