Study of Lisdexamfetamine Sulfate to Treat Cognitive Dysfunction in Multiple Sclerosis

NCT01615887 | Completed Phase 2 Results

• 1 other identifier: NEU2570309B
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple Sclerosis

Outcome Measures

Primary Outcomes (2)

• 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.

  8 weeks

• 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.

  8 Weeks

Secondary Outcomes (5)

• California Verbal Learning Test - 2nd Edition

  8 weeks

• Brief Visuospatial Memory Test - Revised

  8 weeks

• Vitals

  8 weeks

• Vitals (Diastolic Blood Pressure)

  8 weeks

• Vitals (Systolic Blood Pressure)

  8 weeks

Study Arms (2)

lisdexamfetamine sulfate

EXPERIMENTAL

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

Drug: lisdexamfetamine sulfate

Sugar pill

PLACEBO COMPARATOR

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

Drug: placebo

Interventions

lisdexamfetamine sulfate DRUG

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

Also known as: Vyvanse

lisdexamfetamine sulfate

placebo DRUG

sugar pill

Sugar pill

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• State University of New York at Buffalo: lead

Study Sites (1)

Kaleida Health, Jacobs Neurological Institute

Buffalo, New York, 14203, United States

Location

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Lisdexamfetamine Dimesylate

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Dextroamphetamine; Amphetamine; Amphetamines; Phenethylamines; Ethylamines; Amines; Organic Chemicals

Results Point of Contact

• Title: Ralph Benedict
• Organization: SUNY University at Buffalo

benedict@buffalo.edu

716-323-0556

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 23, 2011
• First Posted: June 11, 2012
• Study Start: November 1, 2009
• Primary Completion: August 1, 2011
• Study Completion: August 1, 2011
• Last Updated: September 16, 2022
• Results First Posted: September 16, 2022

Record last verified: 2022-08

Locations

US (1)