Trial Outcomes & Findings for Study of Lisdexamfetamine Sulfate to Treat Cognitive Dysfunction in Multiple Sclerosis (NCT NCT01615887)

Last Updated: 2022-09-16

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

63 participants

Primary outcome timeframe

8 weeks

Results posted on

2022-09-16

Participant Flow

Participant milestones

Participant milestones
Measure	Lisdexamfetamine Sulfate 30mg lisdexamfetamine OD, increased to 70mg OD over 4 weeks and continued on 70mg OD for 4 weeks lisdexamfetamine sulfate: 30mg lisdexamfetamine OD, increased to 70mg OD over 4 weeks and continued on 70mg OD for 4 weeks	Sugar Pill Placebo will be administered in the same fashion as the treatment arm placebo: sugar pill
Overall Study STARTED	41	22
Overall Study COMPLETED	29	19
Overall Study NOT COMPLETED	12	3

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study of Lisdexamfetamine Sulfate to Treat Cognitive Dysfunction in Multiple Sclerosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lisdexamfetamine Sulfate n=29 Participants 30mg lisdexamfetamine OD, increased to 70mg OD over 4 weeks and continued on 70mg OD for 4 weeks lisdexamfetamine sulfate: 30mg lisdexamfetamine OD, increased to 70mg OD over 4 weeks and continued on 70mg OD for 4 weeks	Sugar Pill n=19 Participants Placebo will be administered in the same fashion as the treatment arm placebo: sugar pill	Total n=48 Participants Total of all reporting groups
Age, Continuous	48.7 years STANDARD_DEVIATION 8.0 • n=5 Participants	46.7 years STANDARD_DEVIATION 8.5 • n=7 Participants	47.7 years STANDARD_DEVIATION 8.25 • n=5 Participants
Sex: Female, Male Female	23 Participants n=5 Participants	12 Participants n=7 Participants	35 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	7 Participants n=7 Participants	13 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) White	26 Participants n=5 Participants	18 Participants n=7 Participants	44 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	29 participants n=5 Participants	19 participants n=7 Participants	48 participants n=5 Participants

PRIMARY outcome

Timeframe: 8 weeks

Outcome measures

Outcome measures
Measure	Lisdexamfetamine Sulfate n=29 Participants 30mg lisdexamfetamine OD, increased to 70mg OD over 4 weeks and continued on 70mg OD for 4 weeks lisdexamfetamine sulfate: 30mg lisdexamfetamine OD, increased to 70mg OD over 4 weeks and continued on 70mg OD for 4 weeks	Sugar Pill n=19 Participants Placebo will be administered in the same fashion as the treatment arm placebo: sugar pill
Symbol Digit Modalities Test (SDMT)	36.9 score on a scale Standard Deviation 8.7	46.8 score on a scale Standard Deviation 7.5

PRIMARY outcome

Timeframe: 8 Weeks

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.

Outcome measures

Outcome measures
Measure	Lisdexamfetamine Sulfate n=29 Participants 30mg lisdexamfetamine OD, increased to 70mg OD over 4 weeks and continued on 70mg OD for 4 weeks lisdexamfetamine sulfate: 30mg lisdexamfetamine OD, increased to 70mg OD over 4 weeks and continued on 70mg OD for 4 weeks	Sugar Pill n=19 Participants Placebo will be administered in the same fashion as the treatment arm placebo: sugar pill
Paced Auditory Serial Audition Test (PASAT)	32.0 score on a scale Standard Deviation 12.5	37.4 score on a scale Standard Deviation 12.1

SECONDARY outcome

Timeframe: 8 weeks

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.

Outcome measures

Outcome measures
Measure	Lisdexamfetamine Sulfate n=29 Participants 30mg lisdexamfetamine OD, increased to 70mg OD over 4 weeks and continued on 70mg OD for 4 weeks lisdexamfetamine sulfate: 30mg lisdexamfetamine OD, increased to 70mg OD over 4 weeks and continued on 70mg OD for 4 weeks	Sugar Pill n=19 Participants Placebo will be administered in the same fashion as the treatment arm placebo: sugar pill
California Verbal Learning Test - 2nd Edition	44.9 score on a scale Standard Deviation 11.5	49.2 score on a scale Standard Deviation 10.2

SECONDARY outcome

Timeframe: 8 weeks

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.

Outcome measures

Outcome measures
Measure	Lisdexamfetamine Sulfate n=29 Participants 30mg lisdexamfetamine OD, increased to 70mg OD over 4 weeks and continued on 70mg OD for 4 weeks lisdexamfetamine sulfate: 30mg lisdexamfetamine OD, increased to 70mg OD over 4 weeks and continued on 70mg OD for 4 weeks	Sugar Pill n=19 Participants Placebo will be administered in the same fashion as the treatment arm placebo: sugar pill
Brief Visuospatial Memory Test - Revised	15.2 score on a scale Standard Deviation 6.1	18.7 score on a scale Standard Deviation 5.5

SECONDARY outcome

Timeframe: 8 weeks

Heart rate

Outcome measures

Outcome measures
Measure	Lisdexamfetamine Sulfate n=29 Participants 30mg lisdexamfetamine OD, increased to 70mg OD over 4 weeks and continued on 70mg OD for 4 weeks lisdexamfetamine sulfate: 30mg lisdexamfetamine OD, increased to 70mg OD over 4 weeks and continued on 70mg OD for 4 weeks	Sugar Pill n=19 Participants Placebo will be administered in the same fashion as the treatment arm placebo: sugar pill
Vitals	72.3 beats/min Standard Deviation 11.7	76.9 beats/min Standard Deviation 10.6

SECONDARY outcome

Timeframe: 8 weeks

diastolic blood pressure

Outcome measures

Outcome measures
Measure	Lisdexamfetamine Sulfate n=29 Participants 30mg lisdexamfetamine OD, increased to 70mg OD over 4 weeks and continued on 70mg OD for 4 weeks lisdexamfetamine sulfate: 30mg lisdexamfetamine OD, increased to 70mg OD over 4 weeks and continued on 70mg OD for 4 weeks	Sugar Pill n=19 Participants Placebo will be administered in the same fashion as the treatment arm placebo: sugar pill
Vitals (Diastolic Blood Pressure)	75.1 mm hg (millimeters of mercury) Standard Deviation 11.3	77.7 mm hg (millimeters of mercury) Standard Deviation 7.7

SECONDARY outcome

Timeframe: 8 weeks

systolic blood pressure

Outcome measures

Outcome measures
Measure	Lisdexamfetamine Sulfate n=29 Participants 30mg lisdexamfetamine OD, increased to 70mg OD over 4 weeks and continued on 70mg OD for 4 weeks lisdexamfetamine sulfate: 30mg lisdexamfetamine OD, increased to 70mg OD over 4 weeks and continued on 70mg OD for 4 weeks	Sugar Pill n=19 Participants Placebo will be administered in the same fashion as the treatment arm placebo: sugar pill
Vitals (Systolic Blood Pressure)	127.3 mm hg (millimeters of mercury) Standard Deviation 15.9	121.6 mm hg (millimeters of mercury) Standard Deviation 13.1

Adverse Events

Lisdexamfetamine Sulfate

Serious events: 0 serious events

Other events: 23 other events

Deaths: 0 deaths

Sugar Pill

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Ralph Benedict

SUNY University at Buffalo

Phone: 716-323-0556

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Lisdexamfetamine Sulfate n=41 participants at risk 30mg lisdexamfetamine OD, increased to 70mg OD over 4 weeks and continued on 70mg OD for 4 weeks lisdexamfetamine sulfate: 30mg lisdexamfetamine OD, increased to 70mg OD over 4 weeks and continued on 70mg OD for 4 weeks	Sugar Pill n=22 participants at risk Placebo will be administered in the same fashion as the treatment arm placebo: sugar pill
Gastrointestinal disorders dry mouth	36.6% 15/41 • adverse events data were collected over the 8-week study period. During the first 4 weeks adverse event data was collected weekly and then once more 4 weeks later. Participants were monitored for serious adverse events weekly during the first 4 weeks and then once more 4 weeks later. During this time no serious adverse events were reported by subjects and no objective measures suggested any serious adverse events took place.	9.1% 2/22 • adverse events data were collected over the 8-week study period. During the first 4 weeks adverse event data was collected weekly and then once more 4 weeks later. Participants were monitored for serious adverse events weekly during the first 4 weeks and then once more 4 weeks later. During this time no serious adverse events were reported by subjects and no objective measures suggested any serious adverse events took place.
Gastrointestinal disorders nausea	12.2% 5/41 • adverse events data were collected over the 8-week study period. During the first 4 weeks adverse event data was collected weekly and then once more 4 weeks later. Participants were monitored for serious adverse events weekly during the first 4 weeks and then once more 4 weeks later. During this time no serious adverse events were reported by subjects and no objective measures suggested any serious adverse events took place.	4.5% 1/22 • adverse events data were collected over the 8-week study period. During the first 4 weeks adverse event data was collected weekly and then once more 4 weeks later. Participants were monitored for serious adverse events weekly during the first 4 weeks and then once more 4 weeks later. During this time no serious adverse events were reported by subjects and no objective measures suggested any serious adverse events took place.
Cardiac disorders palpitations	12.2% 5/41 • adverse events data were collected over the 8-week study period. During the first 4 weeks adverse event data was collected weekly and then once more 4 weeks later. Participants were monitored for serious adverse events weekly during the first 4 weeks and then once more 4 weeks later. During this time no serious adverse events were reported by subjects and no objective measures suggested any serious adverse events took place.	4.5% 1/22 • adverse events data were collected over the 8-week study period. During the first 4 weeks adverse event data was collected weekly and then once more 4 weeks later. Participants were monitored for serious adverse events weekly during the first 4 weeks and then once more 4 weeks later. During this time no serious adverse events were reported by subjects and no objective measures suggested any serious adverse events took place.
Cardiac disorders increased heart rate	26.8% 11/41 • adverse events data were collected over the 8-week study period. During the first 4 weeks adverse event data was collected weekly and then once more 4 weeks later. Participants were monitored for serious adverse events weekly during the first 4 weeks and then once more 4 weeks later. During this time no serious adverse events were reported by subjects and no objective measures suggested any serious adverse events took place.	9.1% 2/22 • adverse events data were collected over the 8-week study period. During the first 4 weeks adverse event data was collected weekly and then once more 4 weeks later. Participants were monitored for serious adverse events weekly during the first 4 weeks and then once more 4 weeks later. During this time no serious adverse events were reported by subjects and no objective measures suggested any serious adverse events took place.
Cardiac disorders Increased systolic blood pressure	9.8% 4/41 • adverse events data were collected over the 8-week study period. During the first 4 weeks adverse event data was collected weekly and then once more 4 weeks later. Participants were monitored for serious adverse events weekly during the first 4 weeks and then once more 4 weeks later. During this time no serious adverse events were reported by subjects and no objective measures suggested any serious adverse events took place.	4.5% 1/22 • adverse events data were collected over the 8-week study period. During the first 4 weeks adverse event data was collected weekly and then once more 4 weeks later. Participants were monitored for serious adverse events weekly during the first 4 weeks and then once more 4 weeks later. During this time no serious adverse events were reported by subjects and no objective measures suggested any serious adverse events took place.
Cardiac disorders increased diastolic blood pressure	19.5% 8/41 • adverse events data were collected over the 8-week study period. During the first 4 weeks adverse event data was collected weekly and then once more 4 weeks later. Participants were monitored for serious adverse events weekly during the first 4 weeks and then once more 4 weeks later. During this time no serious adverse events were reported by subjects and no objective measures suggested any serious adverse events took place.	4.5% 1/22 • adverse events data were collected over the 8-week study period. During the first 4 weeks adverse event data was collected weekly and then once more 4 weeks later. Participants were monitored for serious adverse events weekly during the first 4 weeks and then once more 4 weeks later. During this time no serious adverse events were reported by subjects and no objective measures suggested any serious adverse events took place.
Cardiac disorders flushing/feeling warm	7.3% 3/41 • adverse events data were collected over the 8-week study period. During the first 4 weeks adverse event data was collected weekly and then once more 4 weeks later. Participants were monitored for serious adverse events weekly during the first 4 weeks and then once more 4 weeks later. During this time no serious adverse events were reported by subjects and no objective measures suggested any serious adverse events took place.	0.00% 0/22 • adverse events data were collected over the 8-week study period. During the first 4 weeks adverse event data was collected weekly and then once more 4 weeks later. Participants were monitored for serious adverse events weekly during the first 4 weeks and then once more 4 weeks later. During this time no serious adverse events were reported by subjects and no objective measures suggested any serious adverse events took place.
General disorders headache	19.5% 8/41 • adverse events data were collected over the 8-week study period. During the first 4 weeks adverse event data was collected weekly and then once more 4 weeks later. Participants were monitored for serious adverse events weekly during the first 4 weeks and then once more 4 weeks later. During this time no serious adverse events were reported by subjects and no objective measures suggested any serious adverse events took place.	4.5% 1/22 • adverse events data were collected over the 8-week study period. During the first 4 weeks adverse event data was collected weekly and then once more 4 weeks later. Participants were monitored for serious adverse events weekly during the first 4 weeks and then once more 4 weeks later. During this time no serious adverse events were reported by subjects and no objective measures suggested any serious adverse events took place.
General disorders lightheadedness	9.8% 4/41 • adverse events data were collected over the 8-week study period. During the first 4 weeks adverse event data was collected weekly and then once more 4 weeks later. Participants were monitored for serious adverse events weekly during the first 4 weeks and then once more 4 weeks later. During this time no serious adverse events were reported by subjects and no objective measures suggested any serious adverse events took place.	0.00% 0/22 • adverse events data were collected over the 8-week study period. During the first 4 weeks adverse event data was collected weekly and then once more 4 weeks later. Participants were monitored for serious adverse events weekly during the first 4 weeks and then once more 4 weeks later. During this time no serious adverse events were reported by subjects and no objective measures suggested any serious adverse events took place.
General disorders Paresthesias	7.3% 3/41 • adverse events data were collected over the 8-week study period. During the first 4 weeks adverse event data was collected weekly and then once more 4 weeks later. Participants were monitored for serious adverse events weekly during the first 4 weeks and then once more 4 weeks later. During this time no serious adverse events were reported by subjects and no objective measures suggested any serious adverse events took place.	4.5% 1/22 • adverse events data were collected over the 8-week study period. During the first 4 weeks adverse event data was collected weekly and then once more 4 weeks later. Participants were monitored for serious adverse events weekly during the first 4 weeks and then once more 4 weeks later. During this time no serious adverse events were reported by subjects and no objective measures suggested any serious adverse events took place.
Metabolism and nutrition disorders weight loss	7.3% 3/41 • adverse events data were collected over the 8-week study period. During the first 4 weeks adverse event data was collected weekly and then once more 4 weeks later. Participants were monitored for serious adverse events weekly during the first 4 weeks and then once more 4 weeks later. During this time no serious adverse events were reported by subjects and no objective measures suggested any serious adverse events took place.	0.00% 0/22 • adverse events data were collected over the 8-week study period. During the first 4 weeks adverse event data was collected weekly and then once more 4 weeks later. Participants were monitored for serious adverse events weekly during the first 4 weeks and then once more 4 weeks later. During this time no serious adverse events were reported by subjects and no objective measures suggested any serious adverse events took place.
Metabolism and nutrition disorders decreased appetite	26.8% 11/41 • adverse events data were collected over the 8-week study period. During the first 4 weeks adverse event data was collected weekly and then once more 4 weeks later. Participants were monitored for serious adverse events weekly during the first 4 weeks and then once more 4 weeks later. During this time no serious adverse events were reported by subjects and no objective measures suggested any serious adverse events took place.	4.5% 1/22 • adverse events data were collected over the 8-week study period. During the first 4 weeks adverse event data was collected weekly and then once more 4 weeks later. Participants were monitored for serious adverse events weekly during the first 4 weeks and then once more 4 weeks later. During this time no serious adverse events were reported by subjects and no objective measures suggested any serious adverse events took place.
Psychiatric disorders anxiety	12.2% 5/41 • adverse events data were collected over the 8-week study period. During the first 4 weeks adverse event data was collected weekly and then once more 4 weeks later. Participants were monitored for serious adverse events weekly during the first 4 weeks and then once more 4 weeks later. During this time no serious adverse events were reported by subjects and no objective measures suggested any serious adverse events took place.	0.00% 0/22 • adverse events data were collected over the 8-week study period. During the first 4 weeks adverse event data was collected weekly and then once more 4 weeks later. Participants were monitored for serious adverse events weekly during the first 4 weeks and then once more 4 weeks later. During this time no serious adverse events were reported by subjects and no objective measures suggested any serious adverse events took place.
Psychiatric disorders agitation	7.3% 3/41 • adverse events data were collected over the 8-week study period. During the first 4 weeks adverse event data was collected weekly and then once more 4 weeks later. Participants were monitored for serious adverse events weekly during the first 4 weeks and then once more 4 weeks later. During this time no serious adverse events were reported by subjects and no objective measures suggested any serious adverse events took place.	0.00% 0/22 • adverse events data were collected over the 8-week study period. During the first 4 weeks adverse event data was collected weekly and then once more 4 weeks later. Participants were monitored for serious adverse events weekly during the first 4 weeks and then once more 4 weeks later. During this time no serious adverse events were reported by subjects and no objective measures suggested any serious adverse events took place.
Psychiatric disorders mania	9.8% 4/41 • adverse events data were collected over the 8-week study period. During the first 4 weeks adverse event data was collected weekly and then once more 4 weeks later. Participants were monitored for serious adverse events weekly during the first 4 weeks and then once more 4 weeks later. During this time no serious adverse events were reported by subjects and no objective measures suggested any serious adverse events took place.	4.5% 1/22 • adverse events data were collected over the 8-week study period. During the first 4 weeks adverse event data was collected weekly and then once more 4 weeks later. Participants were monitored for serious adverse events weekly during the first 4 weeks and then once more 4 weeks later. During this time no serious adverse events were reported by subjects and no objective measures suggested any serious adverse events took place.
General disorders body aches and cramps	12.2% 5/41 • adverse events data were collected over the 8-week study period. During the first 4 weeks adverse event data was collected weekly and then once more 4 weeks later. Participants were monitored for serious adverse events weekly during the first 4 weeks and then once more 4 weeks later. During this time no serious adverse events were reported by subjects and no objective measures suggested any serious adverse events took place.	0.00% 0/22 • adverse events data were collected over the 8-week study period. During the first 4 weeks adverse event data was collected weekly and then once more 4 weeks later. Participants were monitored for serious adverse events weekly during the first 4 weeks and then once more 4 weeks later. During this time no serious adverse events were reported by subjects and no objective measures suggested any serious adverse events took place.