Multiple Sclerosis
Conditions
Brief summary
The investigation will involve a double-blind, placebo controlled, cross-over study examining the efficacy of armodafinil in improving neurocognitive functioning and reducing cognitive fatigue in MS. Patients who report MS-related cognitive difficulties and perform at least 1 standard deviation below the mean on a brief cognitive screen will be given a thorough neuropsychological evaluation at two time points. Half of the patients will be randomized to receive a single oral dose of lactose placebo prior to the first testing session. After a washout period of one week, they will then receive 250mg of armodafinil prior to a second testing session (P/A group). The other half of patients will be randomized to receive the active drug first. After a washout period of one week, they will receive the placebo prior to a second testing session (A/P group). As plasma levels of armodafinil peak between 2-4 hours after administration, participants will be asked to take a single 250mg capsule 2 hours prior to the scheduled testing sessions.
Interventions
DRUGarmodafinil
Half of the patients will be randomized to receive a single oral dose of placebo prior to the first testing session. After a washout period of one week, they will then receive 250mg of armodafinil prior to a second testing session (P/A group). The other half of patients will be randomized to receive the active drug first. After a washout period of one week, they will receive the placebo prior to a second testing session (A/P group). As plasma levels of armodafinil peak between 2-4 hours after administration, participants will be asked to take a single 250mg capsule 2 hours prior to the scheduled testing sessions.
Sponsors
University of Kansas
University of Missouri, Kansas City
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* relapsing remitting and secondary progressive MS patients * between the ages of 18 and 60 * report cognitive difficulties. * perform 1 sd or more below cut-off on cognitive screening measure
Exclusion criteria
* no history of alcohol/drug abuse or nervous system disorder other than MS * no sensory impairments that might interfere significantly with cognitive testing * no developmental history of learning disability or attention-deficit/hyperactivity disorder * no medical condition other than MS that could substantially affect cognition * no relapse and/or corticosteroid use within four weeks of assessment; * no current use of modafinil, armodafinil or other psychostimulants.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Learning and Memory Measures. | Outcome was assessed after each intervention (2 time points). Time 2 scores were subtracted from time 1 scores. | Testing was completed after first intervention and again after second intervention. Higher scores indicate better performance. Scores from derived by subtracting session 2 scores from session 1 scores. Rey Auditory Verbal Learning Test (RAVLT)- Measure of Verbal Learning (Min = 0; Max = 75). RAVLT Delay - Measure of Delayed Verbal Recall (Min = 0; Max = 15). Brief Visuospatial Memory Test (BVMT) Learning - Measure of Visual Learning (Min = 0; Max = 36). BVMT Delay - Measure of Delayed Visual Recall (Min = 0; Max = 12). |
| CPT -Test of Information Processing Speed | Outcome was assessed after each intervention (2 time points). Time 2 scores were subtracted from time 1 scores. | Lower scores indicate better perforamnce. Scores from derived by subtracting session 2 scores from session 1 scores. Continuous Performance Test (CPT) - Vigilance and reaction time. |
| Stroop | Outcome was assessed after each intervention (2 time points). Time 2 scores were subtracted from time 1 scores. | Stroop - Test of impulsivity (min = 0, max = none). Higher scores indicate better performance. Scores from derived by subtracting session 2 scores from session 1 scores. |
| Word Generation | Outcome was assessed after each intervention (2 time points). Time 2 scores were subtracted from time 1 scores. | Word Generation - Measure of verbal fluency. (Min = 0; No Max. )Higher scores indicate better performance. Scores from derived by subtracting session 2 scores from session 1 scores. |
Countries
United States
Participant flow
Recruitment details
Participants who demonstrated at least mild cognitive impairment on a screening measure were recruited from a large MS neurology clinic in the Midwest from 2009 to 2011.
Participants by arm
| Arm | Count |
|---|---|
| Armodafinil Then Placebo All participants will receive one dose of armodafinil and one dose of placebo in a cross-over design
armodafinil : Half of the patients will be randomized to receive a single oral dose of placebo prior to the first testing session. After a washout period of one week, they will then receive 250mg of armodafinil prior to a second testing session (P/A group). The other half of patients will be randomized to receive the active drug first. After a washout period of one week, they will receive the placebo prior to a second testing session (A/P group). As plasma levels of armodafinil peak between 2-4 hours after administration, participants will be asked to take a single 250mg capsule 2 hours prior to the scheduled testing sessions. | 16 |
| Placebo Then Armodafinil | 17 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Post Intervention (Data Analysis) | imbalance in disease subtype | 1 | 0 |
| Post Intervention (Data Analysis) | poor effort | 1 | 1 |
Baseline characteristics
| Characteristic | Placebo Then Armodafinil | Armodafinil Then Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants | 16 Participants | 33 Participants |
| Age Continuous | 49.94 years STANDARD_DEVIATION 7.22 | 47.71 years STANDARD_DEVIATION 5.89 | 49.15 years STANDARD_DEVIATION 6.54 |
| Region of Enrollment United States | 17 participants | 16 participants | 33 participants |
| Sex: Female, Male Female | 15 Participants | 13 Participants | 28 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 17 | 3 / 16 | 2 / 17 | 1 / 16 |
| serious Total, serious adverse events | 0 / 17 | 0 / 16 | 0 / 17 | 0 / 16 |
Outcome results
Primary
CPT -Test of Information Processing Speed
Lower scores indicate better perforamnce. Scores from derived by subtracting session 2 scores from session 1 scores. Continuous Performance Test (CPT) - Vigilance and reaction time.
Time frame: Outcome was assessed after each intervention (2 time points). Time 2 scores were subtracted from time 1 scores.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Armofafinil | CPT -Test of Information Processing Speed | -1.18 milliseconds | Standard Deviation 37.62 |
| Armodafinil/Placebo | CPT -Test of Information Processing Speed | 15.04 milliseconds | Standard Deviation 50.3 |
Comparison: We used a crossover design to exame whether a single dose of armodafinil would improve cognition in MS. For hypothesis testing analyses, we used a statistical approach that accounts for period (session) effects. We subtracted session 2 performance from session 1 performance on the CPT, yielding a difference score. we conducted an independent samples t test with treatment order as the independent variable (A/P vs. P/A) and the difference score as the dependent variable.p-value: 0.33t-test, 2 sided
Primary
Learning and Memory Measures.
Testing was completed after first intervention and again after second intervention. Higher scores indicate better performance. Scores from derived by subtracting session 2 scores from session 1 scores. Rey Auditory Verbal Learning Test (RAVLT)- Measure of Verbal Learning (Min = 0; Max = 75). RAVLT Delay - Measure of Delayed Verbal Recall (Min = 0; Max = 15). Brief Visuospatial Memory Test (BVMT) Learning - Measure of Visual Learning (Min = 0; Max = 36). BVMT Delay - Measure of Delayed Visual Recall (Min = 0; Max = 12).
Time frame: Outcome was assessed after each intervention (2 time points). Time 2 scores were subtracted from time 1 scores.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo/Armofafinil | Learning and Memory Measures. | Auditory Verbal Learning Test - Learning | -3.38 Items recalled | Standard Deviation 7.32 |
| Placebo/Armofafinil | Learning and Memory Measures. | Aditory Verbal Learning Test Delay | -1.38 Items recalled | Standard Deviation 1.89 |
| Placebo/Armofafinil | Learning and Memory Measures. | Brief Visuospatial Memory Test Learning | .88 Items recalled | Standard Deviation 4.63 |
| Placebo/Armofafinil | Learning and Memory Measures. | Brief Visuospatial Memory Test Delay | .56 Items recalled | Standard Deviation 1.5 |
| Armodafinil/Placebo | Learning and Memory Measures. | Brief Visuospatial Memory Test Delay | -.57 Items recalled | Standard Deviation 2.17 |
| Armodafinil/Placebo | Learning and Memory Measures. | Auditory Verbal Learning Test - Learning | -.07 Items recalled | Standard Deviation 6.06 |
| Armodafinil/Placebo | Learning and Memory Measures. | Brief Visuospatial Memory Test Learning | -1.57 Items recalled | Standard Deviation 5.71 |
| Armodafinil/Placebo | Learning and Memory Measures. | Aditory Verbal Learning Test Delay | 1.93 Items recalled | Standard Deviation 2.7 |
Comparison: We used a crossover design to exame whether a single dose of armodafinil would improve cognition in MS. For hypothesis testing analyses, we used a statistical approach that accounts for period (session) effects. We subtracted session 2 performance from session 1 performance on the RVLT learning, yeilding a difference score. we conducted an independent samples t test with treatment order as the independent variable (A/P vs. P/A) and the difference score as the dependent variable.p-value: =0.19t-test, 2 sided
Comparison: We used a crossover design to exame whether a single dose of armodafinil would improve cognition in MS. For hypothesis testing analyses, we used a statistical approach that accounts for period (session) effects. We subtracted session 2 performance from session 1 performance on the RVLT delay, yielding a difference score. we conducted an independent samples t test with treatment order as the independent variable (A/P vs. P/A) and the difference score as the dependent variable.p-value: =0.0005t-test, 2 sided
Comparison: We used a crossover design to exame whether a single dose of armodafinil would improve cognition in MS. For hypothesis testing analyses, we used a statistical approach that accounts for period (session) effects. We subtracted session 2 performance from session 1 performance on the BVMT learning, yeilding a difference score. we conducted an independent samples t test with treatment order as the independent variable (A/P vs. P/A) and the difference score as the dependent variable.p-value: =0.21t-test, 2 sided
Comparison: We used a crossover design to exame whether a single dose of armodafinil would improve cognition in MS. For hypothesis testing analyses, we used a statistical approach that accounts for period (session) effects. We subtracted session 2 performance from session 1 performance on the BVMT delay, yielding a difference score. we conducted an independent samples t test with treatment order as the independent variable (A/P vs. P/A) and the difference score as the dependent variable.p-value: =0.1t-test, 2 sided
Primary
Stroop
Stroop - Test of impulsivity (min = 0, max = none). Higher scores indicate better performance. Scores from derived by subtracting session 2 scores from session 1 scores.
Time frame: Outcome was assessed after each intervention (2 time points). Time 2 scores were subtracted from time 1 scores.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Armofafinil | Stroop | -1.69 number of colors named | Standard Deviation 3.38 |
| Armodafinil/Placebo | Stroop | -2.86 number of colors named | Standard Deviation 3.72 |
Comparison: We used a crossover design to examine whether a single dose of armodafinil would improve cognition in MS. For hypothesis testing analyses, we used a statistical approach that accounts for period (session) effects. We subtracted session 2 performance from session 1 performance on the Stroop, yielding a difference score. We conducted an independent samples t-test with treatment order as the independent variable (A/P vs. P/A) and the difference score as the dependent variable.p-value: 0.37t-test, 2 sided
Primary
Word Generation
Word Generation - Measure of verbal fluency. (Min = 0; No Max. )Higher scores indicate better performance. Scores from derived by subtracting session 2 scores from session 1 scores.
Time frame: Outcome was assessed after each intervention (2 time points). Time 2 scores were subtracted from time 1 scores.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Armofafinil | Word Generation | -.69 number of words generated | Standard Deviation 5.21 |
| Armodafinil/Placebo | Word Generation | -1.71 number of words generated | Standard Deviation 3.24 |
Comparison: We used a crossover design to examine whether a single dose of armodafinil would improve cognition in MS. For hypothesis testing analyses, we used a statistical approach that accounts for period (session) effects. We subtracted session 2 performance from session 1 performance on the Word Generation, yielding a difference score. We conducted an independent samples t-test with treatment order as the independent variable (A/P vs. P/A) and the difference score as the dependent variable.p-value: 0.53t-test, 2 sided