Ignite Creation Date:
2024-05-05 @ 4:43 PM
Last Modification Date:
2024-10-26 @ 9:23 AM
Study NCT ID:
NCT00300716
Status:
COMPLETED
Last Update Posted:
2019-10-15
First Post:
2006-03-08
Brief Title:
Trial of Memantine for Cognitive Impairment in Multiple Sclerosis
Sponsor:
Oregon Health and Science University
Organization:
Oregon Health and Science University
Study Overview
Official Title:
Double Blind Placebo Controlled Pilot Trial of Memantine for Cognitive Impairment in Multiple Sclerosis
Status:
COMPLETED
Status Verified Date:
2019-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study is designed to determine whether memantine is an effective treatment for memory and cognitive problems associated with multiple sclerosis when compared to placebo
Detailed Description:
Objective
The objective of this pilot project is to conduct a clinical trial to assess the efficacy of memantine as a treatment for cognitive dysfunction in multiple sclerosis MS We hypothesize that MS patients with cognitive impairment treated with memantine will demonstrate an improvement in performance on a neuropsychological test battery as compared to placebo treated patients
Background and Significance
Cognitive dysfunction is a major cause of disability in multiple sclerosis MS The estimated prevalence of cognitive dysfunction in the MS population is 45 to 65 MS patients with cognitive dysfunction have fewer social interactions more sexual dysfunction greater difficulty with household tasks and higher unemployment than those with normal cognition At present there is no effective pharmacological symptomatic treatment for the cognitive dysfunction of MS One agent that may have some benefit in treating this condition is the N-methyl-D-aspartate NMDA receptor antagonist memantine
Memantine is a NMDA antagonist that has been shown to be effective in treating Alzheimers disease Glutamate toxicity has been implicated in the pathogenesis of a variety of neurologic diseases including MS Glutamate receptor activation may be involved both in mediation of neural injury and in neuronal dysfunction By blocking NMDA receptors memantine may both improve neuronal function explaining symptomatic improvement in some Alzheimers patients and slow progressive neuronal death potentially resulting in a slowing of cognitive decline in Alzheimers patients The pathogenesis of cognitive dysfunction in MS relates at least in part to the extent of cerebral demyelination axonal loss and atrophy Some cognitive dysfunction is reversible Reduction in inflammation can result in improvement in cognitive performance What role NMDA receptors and glutamate toxicity may play in cognitive dysfunction is uncertain but given the lack of any treatment for cognitive dysfunction in MS performing a pilot trial of memantine in MS is clearly warranted
Overall Design
This is a placebo-controlled double-blinded randomized parallel-group pilot study of 16 weeks duration in MS patients with cognitive impairment There will be 73 patients per treatment arm among all sites The intervention arm will receive 20 mg of memantine a day Randomization into each treatment arm will be stratified on age and CVLT score A double-blind placebo controlled trial is critical to perform even for a pilot trial Both learning and placebo effect are likely to improve the cognitive performance of some subjects An open labeled trial would likely show some improvement in the patients but the results would not be interpretable
Memantine
Both memantine and the placebo will be provided by Forest Laboratories Inc
Scheduled Visits
Visit 1
The subject will receive a consent form After signing visual acuity will be tested The Multiple Sclerosis Screening Neuropsychological Questionnaire MSNQ and the Modified Neuropsychiatric Inventory MNPI will be given to the primary caregiver if present or to the patient instructing him to have the primary caregiver fill it out and return it in the next visit They will receive the first half of the neuropsychological test battery which includes the Paced Auditory Serial Addition Test PASAT and California Verbal Learning Test II CVLT-II They will also receive the Beck Depression Inventory BDI Women of childbearing potential will be asked to give a urine sample for a pregnancy test beta HCG At this point patients will be informed whether they have met the full criteria for enrollment If they qualify then they will receive the second half of the neuropsychological tests Controlled Oral Word Association Test Stroop Color And Word Association Test Symbol Digit Modalities Test and Delis-Kaplan Executive Function System This visit will last approximately 1½ hour if the patient does not qualify for the study and 2 hours if they qualify
Visit 2
The subjects will receive the Fatigue Severity Scale FSS Modified Fatigue Impact Scale MFIS the Medical Outcomes Study 36 Item Short Form Health Survey SF-36 and the Perceived Deficits Questionnaire PDQ from the Multiple Sclerosis Quality of Life Inventory MSQLI A physical exam and a neurological exam will be performed Memantine and placebo pills will be dispensed the neurological exam will include the Expanded Disability Status Scale a 25 feet timed walk and the nine-hole peg test The starting dose of memantine will be 5 mg once daily The dose will be increased in 5 mg increments to 10 mgday 5 mg twice a day 15 mgday 5 mg and 10 mg as separate doses and 20 mgday 10 mg twice a day over 4 weeks and then continued at 20 mg for the rest of the study In case of intolerable side effects when titrating the dose up the dose can be decreased to the previously tolerated dose This visit will last 1 12 hours
Telephone follow-up
Four telephone follow-up visits will be carried-out for all enrolled subjects between Visits 2 and 3 These will occur at two weeks after Visit 2 and again at four seven and eleven weeks after Visit 2 These calls will review study procedures check for compliance and reports of side effects The person calling should be different from the person that administers the neuropsychological tests The total time for the telephone visit is 15 minutes
Side effect evaluation visit
If any unexpected side effects occur subjects will be evaluated with a physical exam and a neurological exam This visit will last approximately 1 hour Relapses will be documented as adverse events and the evaluation will include the EDSS timed walk and 9 hole peg test
Visit 3
Subjects will return to clinic for the final assessment 4 weeks after the last telephone follow-up visit At this visit subjects will complete the full neuropsychological test battery The SF-36 and PDQ BDI FSS and MFIS will be administered The MSNQ and the MNPI will be given to the caregiver A repeat neurological and physical exam will be performed This visit will last 2 ½ hours
The objective of this pilot project is to conduct a clinical trial to assess the efficacy of memantine as a treatment for cognitive dysfunction in multiple sclerosis MS We hypothesize that MS patients with cognitive impairment treated with memantine will demonstrate an improvement in performance on a neuropsychological test battery as compared to placebo treated patients
Background and Significance
Cognitive dysfunction is a major cause of disability in multiple sclerosis MS The estimated prevalence of cognitive dysfunction in the MS population is 45 to 65 MS patients with cognitive dysfunction have fewer social interactions more sexual dysfunction greater difficulty with household tasks and higher unemployment than those with normal cognition At present there is no effective pharmacological symptomatic treatment for the cognitive dysfunction of MS One agent that may have some benefit in treating this condition is the N-methyl-D-aspartate NMDA receptor antagonist memantine
Memantine is a NMDA antagonist that has been shown to be effective in treating Alzheimers disease Glutamate toxicity has been implicated in the pathogenesis of a variety of neurologic diseases including MS Glutamate receptor activation may be involved both in mediation of neural injury and in neuronal dysfunction By blocking NMDA receptors memantine may both improve neuronal function explaining symptomatic improvement in some Alzheimers patients and slow progressive neuronal death potentially resulting in a slowing of cognitive decline in Alzheimers patients The pathogenesis of cognitive dysfunction in MS relates at least in part to the extent of cerebral demyelination axonal loss and atrophy Some cognitive dysfunction is reversible Reduction in inflammation can result in improvement in cognitive performance What role NMDA receptors and glutamate toxicity may play in cognitive dysfunction is uncertain but given the lack of any treatment for cognitive dysfunction in MS performing a pilot trial of memantine in MS is clearly warranted
Overall Design
This is a placebo-controlled double-blinded randomized parallel-group pilot study of 16 weeks duration in MS patients with cognitive impairment There will be 73 patients per treatment arm among all sites The intervention arm will receive 20 mg of memantine a day Randomization into each treatment arm will be stratified on age and CVLT score A double-blind placebo controlled trial is critical to perform even for a pilot trial Both learning and placebo effect are likely to improve the cognitive performance of some subjects An open labeled trial would likely show some improvement in the patients but the results would not be interpretable
Memantine
Both memantine and the placebo will be provided by Forest Laboratories Inc
Scheduled Visits
Visit 1
The subject will receive a consent form After signing visual acuity will be tested The Multiple Sclerosis Screening Neuropsychological Questionnaire MSNQ and the Modified Neuropsychiatric Inventory MNPI will be given to the primary caregiver if present or to the patient instructing him to have the primary caregiver fill it out and return it in the next visit They will receive the first half of the neuropsychological test battery which includes the Paced Auditory Serial Addition Test PASAT and California Verbal Learning Test II CVLT-II They will also receive the Beck Depression Inventory BDI Women of childbearing potential will be asked to give a urine sample for a pregnancy test beta HCG At this point patients will be informed whether they have met the full criteria for enrollment If they qualify then they will receive the second half of the neuropsychological tests Controlled Oral Word Association Test Stroop Color And Word Association Test Symbol Digit Modalities Test and Delis-Kaplan Executive Function System This visit will last approximately 1½ hour if the patient does not qualify for the study and 2 hours if they qualify
Visit 2
The subjects will receive the Fatigue Severity Scale FSS Modified Fatigue Impact Scale MFIS the Medical Outcomes Study 36 Item Short Form Health Survey SF-36 and the Perceived Deficits Questionnaire PDQ from the Multiple Sclerosis Quality of Life Inventory MSQLI A physical exam and a neurological exam will be performed Memantine and placebo pills will be dispensed the neurological exam will include the Expanded Disability Status Scale a 25 feet timed walk and the nine-hole peg test The starting dose of memantine will be 5 mg once daily The dose will be increased in 5 mg increments to 10 mgday 5 mg twice a day 15 mgday 5 mg and 10 mg as separate doses and 20 mgday 10 mg twice a day over 4 weeks and then continued at 20 mg for the rest of the study In case of intolerable side effects when titrating the dose up the dose can be decreased to the previously tolerated dose This visit will last 1 12 hours
Telephone follow-up
Four telephone follow-up visits will be carried-out for all enrolled subjects between Visits 2 and 3 These will occur at two weeks after Visit 2 and again at four seven and eleven weeks after Visit 2 These calls will review study procedures check for compliance and reports of side effects The person calling should be different from the person that administers the neuropsychological tests The total time for the telephone visit is 15 minutes
Side effect evaluation visit
If any unexpected side effects occur subjects will be evaluated with a physical exam and a neurological exam This visit will last approximately 1 hour Relapses will be documented as adverse events and the evaluation will include the EDSS timed walk and 9 hole peg test
Visit 3
Subjects will return to clinic for the final assessment 4 weeks after the last telephone follow-up visit At this visit subjects will complete the full neuropsychological test battery The SF-36 and PDQ BDI FSS and MFIS will be administered The MSNQ and the MNPI will be given to the caregiver A repeat neurological and physical exam will be performed This visit will last 2 ½ hours
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None