Back to resultsEfficacy and Safety of 4-aminopyridine on Cognitive Performance and Motor Function of Patients With Multiple Sclerosis
Primary Purpose
Multiple Sclerosis
Status
Completed
Phase
Phase 2
Locations
Mexico
Study Type
Interventional
Intervention
4-aminopyridine
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Sclerosis focused on measuring Cognitive function, Multiple sclerosis, 4-aminopyridine, Fatigue
Eligibility Criteria
Inclusion Criteria: Patients with multiple sclerosis (MS) are eligible for the study if they meet the following criteria:
- Relapsing recurrent MS with an evolution of at last 6 months before the study began.
- Both males and females, aged 20 - 65 years
- Neurologic Expanded Disability Status Scale (EDSS) 3 - 7
- Who are in first-line immunomodulatory therapy and have a stable disease
- No more than one outbreak per year.
- The absence of antiepileptic antecedent and electroencephalogram without epileptic activity.
- For females: postmenopausal or surgically sterile, or using an acceptable method of birth control
Exclusion Criteria:
- History of cardiovascular disease (syncope, arrhythmia, or myocardial infarction within the last two years), systolic blood pressure greater than 150 or less than 70 mm Hg, diastolic blood pressure greater than 110 or less than 50 mm Hg, or heart rate greater than 110 or less than 50 beats/minute; impaired hepatic function (total hepatic enzyme or bilirubin levels greater than 2 times the upper limits of normal) or impaired renal function (creatinine level greater than 2 times the upper limits of normal) less than 6 months before the study
- Known allergy to pyridine-containing drugs
- Neurologic, degenerative, or psychiatric disorders that would impair the patient's ability to complete the protocol
- Any illness or abnormality that would jeopardize patient safety or interfere with the conduct of the study
- History of substance abuse
- Inability to discontinue excluded concomitant drug therapy
Sites / Locations
- Hospital de Especialidades, CMN Siglo XXI
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
4-aminopyridine treatment
Placebo
Arm Description
4-aminopyridine is given as gelatin capsules containing 4-aminopyridine 10 mg and microcrystalline cellulose as the excipient. Each patient will take two capsules every 8 hours after meals, for a total of 6 capsules/day. The 4-aminopyridine dosage will increase 10 mg/4 weeks by substitution of placebo instead of 4-aminopyridine capsules; such that patients will receive from 40 to 60 mg. distribute in 6capsules/day throughout the study.
Patients randomized to the placebo sequence will receive placebo for 20 weeks after the run-in period. They will be blinded to the fact that they are taking placebo, and capsules will be identical in appearance to the intervention capsules.
Outcomes
Primary Outcome Measures
The Brief Repeatable Battery of Rao
Neuropsychological tests to assess: verbal fluency. Participants have to say as many words as possible from a category in a given time 60 Sec (F, A, S) Max score 72 and min score 19 words. Higher scores indicate a better cognitive performance.
Integrated Program of Neuropsychological Exploration Test Barcelona
Integrated Program of Neuropsychological Exploration Test Barcelona: Digit Span Forward (DSF), (attention spam and improved scoring metrics significantly enhance the precision of DSF assessments of short-term verbal memory). Digit sequences are presented beginning with a length of two digits and two trials are presented at each increasing list length. Max score 8 and min score 0 digits. Higher scores indicate a better cognitive performance.
Rey-Osterrieth Complex Figure Test (ROCF)
The purpose of this test is to assess visual-spatial constructional ability and visual memory. The time required to copy the drawing is recorded. Less time indicates a better performance and more time indicates a worse outcome (min score 60 and max score 300 seconds).
Five Digit Test (FDT). Processing Speed
Processing speed information (which includes reading, count, and alternation speed). Cards with a different number of stimuli are shown to the patient, who has to read, count, and respond to a change of instructions (alternation). Reading speed (min 12, max 31+ seconds), counting speed (min 14, max 28+ seconds), and alternation speed (min 26, max 56+ seconds) are recorded. Less speed corresponds to a better outcome.
Wisconsin Card Sorting Test (WCST)
Is used primarily to assess perseveration and abstract thinking, allows the clinician to assess the following 'frontal' lobe functions: strategic planning, organised searching, utilising environmental feedback to shift cognitive sets, directing behaviour toward achieving a goal. WCST measures abstract reasoning and ability to alter problem solving strategies. Patients are given 128 response cards and 4 stimulus cards and asked to match each stimulus card to 1 pile of response cards. The patient is not told how to match the cards, only "right" or "wrong" to each placement. The examiner may change matching rules during the test. Perseveration errors occur when subject repeats the same error no matter how many times they are told the placement is wrong. Higher scores indicate a worse cognitive performance (min=0-3, max=58-126)
Color Trails Test (CTT)
Measure sustained attention. The CTT uses numbered coloured circles and universal sign language symbols. The circles are printed with vivid pink or yellow backgrounds that are perceptible to colourblind individuals. For the Colour Trails 1 trial, the respondent uses a pencil to rapidly connect circles numbered 1 through 25 in sequence. Less time indicates better performance (min=10, max= 240).
Tower Of London (TOL). Total Moves and Total Correct Moves
Measures higher order problem-solving ability. The information it provides is not only useful when assessing frontal lobe damage, but also when evaluating attention disorders and executive functioning difficulties. The administrator arranges red, green, and blue beads on a peg board to match the configuration in the diagram. The patient is asked to replicate the configuration on a second peg board. Scores are calculated for Total Correct Moves and Total Moves. Total moves: higher scores indicate a worse cognitive performance (min= 0, max=58+); Total correct higher scores indicate a better cognitive performance (min=0, max=10).
Tower Of London (TOL). Execution Time and Problem-solving Time
Measures higher-order problem-solving ability. The information it provides is not only useful when assessing frontal lobe damage, but also when evaluating attention disorders and executive functioning difficulties. The administrator arranges red, green, and blue beads on a peg board to match the configuration in the diagram. The patient is asked to replicate the configuration on a second peg board. Scores are calculated for Total Execution Time (since the patient performs the first move until he ends the test), Total Problem-Solving Time (the sum of planning and execution times). Total execution time higher scores indicate a worse outcome (min= 0-78, max=564+ seconds), Total problem-solving time higher scores indicate a worse outcome (min= 0-56, max=500+ seconds).
Secondary Outcome Measures
Improved Physical Capacity
The Expanded Disability Status Scale (EDSS) is a method of quantifying disability in multiple sclerosis and monitoring changes in the level of disability over time. It is widely used in clinical trials and in the assessment of people with MS. The EDSS scale ranges from 0 to 10 in 0.5 unit increments that represent higher levels of disability. Scoring is based on an examination by a neurologist. The first levels 1.0 to 4.5 refers to people with a high degree of ambulatory ability and the subsequent levels 5.0 to 9.5 refers to the loss of ambulatory ability. It also provides eight subscale measurements called Functional System (FS) scores. The levels of function within each category refer to the eight FS affected by MS: The FS are scored on a scale of 0 (low level of problems) to 5 (high level of problems) to best reflect the level of disability observed clinically.
Fatigue
The Fatigue Severity Scale (FSS) is one of the most frequently used inventories for measuring fatigue in people with chronic illnesses. The FSS questionnaire is comprised of nine statements inquiring about the examinee's sleep habits over the preceding week. Ratings are on a 7-point Likert scale, where higher scores indicate how strongly the patient agrees with the nine statements.Scale. Scoring using a bimodal response system or a Likert score with weights assigned to each response choice. Likert or bimodal rating scales with 4 response options. For the Likert Scale: better than usual= 0, no more than usual= 1, worse than usual= 2, much worse than usual= 3. For the bimodal scale: better than usual= 0, no more than usual= 0, worse than usual= 1, much worse than usual= 1. Sum all items for a total score. Score range. Range is 0 -11 for bimodal response format. Interpretation of scores. Higher score indicates more fatigue. Self report scale
Walk
Timed 25 Foot Walk Test (T25-FW). The T25-FW is a quantitative mobility and leg function performance test based on a timed 25-walk. The patient is directed to one end of a clearly marked 25-foot course and is instructed to walk 25 feet as quickly as possible, but safely. The time is calculated from the initiation of the instruction to start and ends when the patient has reached the 25-foot mark. The task is immediately administered again by having the patient walk back the same distance. Patients may use assistive devices when doing this task. TIME LIMIT PER TRIAL (2) 3 minutes (180 seconds) per trial.
Number of Participants With Abnormal Studies
Safety surveillance will be done every two weeks from the beginning of the study, intentionally searching for adverse events (AE). EEG (Diffuse or focal cerebral dysfunction through demonstration of background slowing or presence of epileptiform activity assessed by a neurophysiologist) and laboratory tests (Presence of values higher of the normal value established by local laboratory and related to the administration of treatments), blood and urine samples: creatinine, blood urea nitrogen, total cholesterol, triglycerides, total direct, and indirect bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, creatinine kinase, lactic acid dehydrogenase, amylase and lipase. A complete blood cell count with differentials and a routine urinalysis and urine culture also obtained at each visit, will be done before the patients take 40, 50 and 60 mg/day. The number of participants with abnormal studies were reported.
Full Information
NCT ID
NCT02280096
First Posted
October 10, 2014
Last Updated
August 6, 2019
Sponsor
Coordinación de Investigación en Salud, Mexico
1. Study Identification
Unique Protocol Identification Number
NCT02280096
Brief Title
Efficacy and Safety of 4-aminopyridine on Cognitive Performance and Motor Function of Patients With Multiple Sclerosis
Official Title
Efficacy and Safety of 4-aminopyridine on Cognitive Performance and Motor Function of Patients With Multiple Sclerosis. Randomized, Blinded, Placebo-controlled Clinical Trial.
Study Type
Interventional
2. Study Status
Record Verification Date
February 2017
Overall Recruitment Status
Completed
Study Start Date
October 2014 (undefined)
Primary Completion Date
February 2016 (Actual)
Study Completion Date
February 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Coordinación de Investigación en Salud, Mexico
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Twenty four relapsing-remitting multiple sclerosis (RRMS) patients over the age of 18, with similar degree of disability, and with an evolution of at last 6 months, who are in first-line immunomodulatory therapy and have a stable disease (no more than one outbreak per year) will be included in the present study. Patients will be administered a neuropsychological test battery selected for this study and divided into two sessions of one and a half-hour each. Emotional state will be assessed with the Beck Depression Inventory in a different session. Cognitive impairment is defined as the alteration of two or more neuropsychological tests. Patients will be divided randomly into two groups where one will receive placebo and the other one 4-Aminopyridine (4-AP) for a period of 22 weeks in increasing doses.
Detailed Description
Consecutive patients with stable multiple sclerosis are being recruited from the neurological services of Social Security Mexican Institute (IMSS) at the National Medical Center (CMN) "Siglo XXI" Specialties Hospital over the period of 1 year. Of those meeting inclusion criteria, 24 will be selected for the study. After signing an informed consent, they will be randomized into 12 for the intervention arm and 12 for the placebo arm. All patients will receive capsules for daily consumption according to their assignment, with no visible difference between capsules. Dosage will be 6.5-7.5 mg/kg to a limit of 50 mg. These capsules will be taken for a period of 22 weeks. A battery of neuropsychological tests will be administered at baseline, after 22 weeks, and after an additional 22 weeks of follow-up to assess cognitive performance and motor function. Emotional state will be assessed with the Beck Depression Inventory at each of the three afore mentioned points.
After the follow-up period, all test results will be analyzed and compared to determine the efficacy and safety of 4-aminopyridine on the cognitive performance and motor function of patients. Mann-Whitney U will be used for statistical analysis.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis
Keywords
Cognitive function, Multiple sclerosis, 4-aminopyridine, Fatigue
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
24 (Actual)
8. Arms, Groups, and Interventions
Arm Title
4-aminopyridine treatment
Arm Type
Active Comparator
Arm Description
4-aminopyridine is given as gelatin capsules containing 4-aminopyridine 10 mg and microcrystalline cellulose as the excipient. Each patient will take two capsules every 8 hours after meals, for a total of 6 capsules/day. The 4-aminopyridine dosage will increase 10 mg/4 weeks by substitution of placebo instead of 4-aminopyridine capsules; such that patients will receive from 40 to 60 mg. distribute in 6capsules/day throughout the study.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Patients randomized to the placebo sequence will receive placebo for 20 weeks after the run-in period. They will be blinded to the fact that they are taking placebo, and capsules will be identical in appearance to the intervention capsules.
Intervention Type
Drug
Intervention Name(s)
4-aminopyridine
Other Intervention Name(s)
4-AP
Intervention Description
Each patient will take two capsules every 8 hours after meals, for a total of 6 capsules/day. The 4-aminopyridine dosage will increase 10 mg/4 weeks by substitution of placebo instead of 4-aminopyridine capsules; such that patients will receive from 40 to 60 mg. distribute in 6capsules/day throughout the study.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Microcrystalline Cellulose
Intervention Description
The placebo arm will include Microcrystalline Cellulose placebo
Primary Outcome Measure Information:
Title
The Brief Repeatable Battery of Rao
Description
Neuropsychological tests to assess: verbal fluency. Participants have to say as many words as possible from a category in a given time 60 Sec (F, A, S) Max score 72 and min score 19 words. Higher scores indicate a better cognitive performance.
Time Frame
10-15 minutes
Title
Integrated Program of Neuropsychological Exploration Test Barcelona
Description
Integrated Program of Neuropsychological Exploration Test Barcelona: Digit Span Forward (DSF), (attention spam and improved scoring metrics significantly enhance the precision of DSF assessments of short-term verbal memory). Digit sequences are presented beginning with a length of two digits and two trials are presented at each increasing list length. Max score 8 and min score 0 digits. Higher scores indicate a better cognitive performance.
Time Frame
7-10 min
Title
Rey-Osterrieth Complex Figure Test (ROCF)
Description
The purpose of this test is to assess visual-spatial constructional ability and visual memory. The time required to copy the drawing is recorded. Less time indicates a better performance and more time indicates a worse outcome (min score 60 and max score 300 seconds).
Time Frame
10-15 minutes
Title
Five Digit Test (FDT). Processing Speed
Description
Processing speed information (which includes reading, count, and alternation speed). Cards with a different number of stimuli are shown to the patient, who has to read, count, and respond to a change of instructions (alternation). Reading speed (min 12, max 31+ seconds), counting speed (min 14, max 28+ seconds), and alternation speed (min 26, max 56+ seconds) are recorded. Less speed corresponds to a better outcome.
Time Frame
8-10 min
Title
Wisconsin Card Sorting Test (WCST)
Description
Is used primarily to assess perseveration and abstract thinking, allows the clinician to assess the following 'frontal' lobe functions: strategic planning, organised searching, utilising environmental feedback to shift cognitive sets, directing behaviour toward achieving a goal. WCST measures abstract reasoning and ability to alter problem solving strategies. Patients are given 128 response cards and 4 stimulus cards and asked to match each stimulus card to 1 pile of response cards. The patient is not told how to match the cards, only "right" or "wrong" to each placement. The examiner may change matching rules during the test. Perseveration errors occur when subject repeats the same error no matter how many times they are told the placement is wrong. Higher scores indicate a worse cognitive performance (min=0-3, max=58-126)
Time Frame
10-15 minutes
Title
Color Trails Test (CTT)
Description
Measure sustained attention. The CTT uses numbered coloured circles and universal sign language symbols. The circles are printed with vivid pink or yellow backgrounds that are perceptible to colourblind individuals. For the Colour Trails 1 trial, the respondent uses a pencil to rapidly connect circles numbered 1 through 25 in sequence. Less time indicates better performance (min=10, max= 240).
Time Frame
5-8 minutes
Title
Tower Of London (TOL). Total Moves and Total Correct Moves
Description
Measures higher order problem-solving ability. The information it provides is not only useful when assessing frontal lobe damage, but also when evaluating attention disorders and executive functioning difficulties. The administrator arranges red, green, and blue beads on a peg board to match the configuration in the diagram. The patient is asked to replicate the configuration on a second peg board. Scores are calculated for Total Correct Moves and Total Moves. Total moves: higher scores indicate a worse cognitive performance (min= 0, max=58+); Total correct higher scores indicate a better cognitive performance (min=0, max=10).
Time Frame
25-30 minutes
Title
Tower Of London (TOL). Execution Time and Problem-solving Time
Description
Measures higher-order problem-solving ability. The information it provides is not only useful when assessing frontal lobe damage, but also when evaluating attention disorders and executive functioning difficulties. The administrator arranges red, green, and blue beads on a peg board to match the configuration in the diagram. The patient is asked to replicate the configuration on a second peg board. Scores are calculated for Total Execution Time (since the patient performs the first move until he ends the test), Total Problem-Solving Time (the sum of planning and execution times). Total execution time higher scores indicate a worse outcome (min= 0-78, max=564+ seconds), Total problem-solving time higher scores indicate a worse outcome (min= 0-56, max=500+ seconds).
Time Frame
25-30 minutes
Secondary Outcome Measure Information:
Title
Improved Physical Capacity
Description
The Expanded Disability Status Scale (EDSS) is a method of quantifying disability in multiple sclerosis and monitoring changes in the level of disability over time. It is widely used in clinical trials and in the assessment of people with MS. The EDSS scale ranges from 0 to 10 in 0.5 unit increments that represent higher levels of disability. Scoring is based on an examination by a neurologist. The first levels 1.0 to 4.5 refers to people with a high degree of ambulatory ability and the subsequent levels 5.0 to 9.5 refers to the loss of ambulatory ability. It also provides eight subscale measurements called Functional System (FS) scores. The levels of function within each category refer to the eight FS affected by MS: The FS are scored on a scale of 0 (low level of problems) to 5 (high level of problems) to best reflect the level of disability observed clinically.
Time Frame
15-20 minutes
Title
Fatigue
Description
The Fatigue Severity Scale (FSS) is one of the most frequently used inventories for measuring fatigue in people with chronic illnesses. The FSS questionnaire is comprised of nine statements inquiring about the examinee's sleep habits over the preceding week. Ratings are on a 7-point Likert scale, where higher scores indicate how strongly the patient agrees with the nine statements.Scale. Scoring using a bimodal response system or a Likert score with weights assigned to each response choice. Likert or bimodal rating scales with 4 response options. For the Likert Scale: better than usual= 0, no more than usual= 1, worse than usual= 2, much worse than usual= 3. For the bimodal scale: better than usual= 0, no more than usual= 0, worse than usual= 1, much worse than usual= 1. Sum all items for a total score. Score range. Range is 0 -11 for bimodal response format. Interpretation of scores. Higher score indicates more fatigue. Self report scale
Time Frame
10 minutes
Title
Walk
Description
Timed 25 Foot Walk Test (T25-FW). The T25-FW is a quantitative mobility and leg function performance test based on a timed 25-walk. The patient is directed to one end of a clearly marked 25-foot course and is instructed to walk 25 feet as quickly as possible, but safely. The time is calculated from the initiation of the instruction to start and ends when the patient has reached the 25-foot mark. The task is immediately administered again by having the patient walk back the same distance. Patients may use assistive devices when doing this task. TIME LIMIT PER TRIAL (2) 3 minutes (180 seconds) per trial.
Time Frame
5-10 minutes
Title
Number of Participants With Abnormal Studies
Description
Safety surveillance will be done every two weeks from the beginning of the study, intentionally searching for adverse events (AE). EEG (Diffuse or focal cerebral dysfunction through demonstration of background slowing or presence of epileptiform activity assessed by a neurophysiologist) and laboratory tests (Presence of values higher of the normal value established by local laboratory and related to the administration of treatments), blood and urine samples: creatinine, blood urea nitrogen, total cholesterol, triglycerides, total direct, and indirect bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, creatinine kinase, lactic acid dehydrogenase, amylase and lipase. A complete blood cell count with differentials and a routine urinalysis and urine culture also obtained at each visit, will be done before the patients take 40, 50 and 60 mg/day. The number of participants with abnormal studies were reported.
Time Frame
22 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with multiple sclerosis (MS) are eligible for the study if they meet the following criteria:
Relapsing recurrent MS with an evolution of at last 6 months before the study began.
Both males and females, aged 20 - 65 years
Neurologic Expanded Disability Status Scale (EDSS) 3 - 7
Who are in first-line immunomodulatory therapy and have a stable disease
No more than one outbreak per year.
The absence of antiepileptic antecedent and electroencephalogram without epileptic activity.
For females: postmenopausal or surgically sterile, or using an acceptable method of birth control
Exclusion Criteria:
History of cardiovascular disease (syncope, arrhythmia, or myocardial infarction within the last two years), systolic blood pressure greater than 150 or less than 70 mm Hg, diastolic blood pressure greater than 110 or less than 50 mm Hg, or heart rate greater than 110 or less than 50 beats/minute; impaired hepatic function (total hepatic enzyme or bilirubin levels greater than 2 times the upper limits of normal) or impaired renal function (creatinine level greater than 2 times the upper limits of normal) less than 6 months before the study
Known allergy to pyridine-containing drugs
Neurologic, degenerative, or psychiatric disorders that would impair the patient's ability to complete the protocol
Any illness or abnormality that would jeopardize patient safety or interfere with the conduct of the study
History of substance abuse
Inability to discontinue excluded concomitant drug therapy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Claudia Arreola Mora, MS
Organizational Affiliation
Instituto Mexicano del Seguro Social
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Israel Grijalva, PhD
Organizational Affiliation
Instituto Mexicano del Seguro Social
Official's Role
Study Director
Facility Information:
Facility Name
Hospital de Especialidades, CMN Siglo XXI
City
Mexico City
State/Province
Distrito Federal
ZIP/Postal Code
06725
Country
Mexico
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
24290498
Citation
Ruck T, Bittner S, Simon OJ, Gobel K, Wiendl H, Schilling M, Meuth SG. Long-term effects of dalfampridine in patients with multiple sclerosis. J Neurol Sci. 2014 Feb 15;337(1-2):18-24. doi: 10.1016/j.jns.2013.11.011. Epub 2013 Nov 16.
Results Reference
background
PubMed Identifier
16643949
Citation
Amato MP, Portaccio E, Zipoli V. Are there protective treatments for cognitive decline in MS? J Neurol Sci. 2006 Jun 15;245(1-2):183-6. doi: 10.1016/j.jns.2005.07.017. Epub 2006 Apr 27.
Results Reference
background
PubMed Identifier
15327047
Citation
Romani A, Bergamaschi R, Candeloro E, Alfonsi E, Callieco R, Cosi V. Fatigue in multiple sclerosis: multidimensional assessment and response to symptomatic treatment. Mult Scler. 2004 Aug;10(4):462-8. doi: 10.1191/1352458504ms1051oa.
Results Reference
background
PubMed Identifier
11795455
Citation
Rossini PM, Pasqualetti P, Pozzilli C, Grasso MG, Millefiorini E, Graceffa A, Carlesimo GA, Zibellini G, Caltagirone C. Fatigue in progressive multiple sclerosis: results of a randomized, double-blind, placebo-controlled, crossover trial of oral 4-aminopyridine. Mult Scler. 2001 Dec;7(6):354-8. doi: 10.1177/135245850100700602.
Results Reference
background
PubMed Identifier
7936300
Citation
Smits RC, Emmen HH, Bertelsmann FW, Kulig BM, van Loenen AC, Polman CH. The effects of 4-aminopyridine on cognitive function in patients with multiple sclerosis: a pilot study. Neurology. 1994 Sep;44(9):1701-5. doi: 10.1212/wnl.44.9.1701.
Results Reference
background
PubMed Identifier
30593980
Citation
Arreola-Mora C, Silva-Pereyra J, Fernandez T, Paredes-Cruz M, Bertado-Cortes B, Grijalva I. Effects of 4-aminopyridine on attention and executive functions of patients with multiple sclerosis: Randomized, double-blind, placebo-controlled clinical trial. Preliminary report. Mult Scler Relat Disord. 2019 Feb;28:117-124. doi: 10.1016/j.msard.2018.12.026. Epub 2018 Dec 19.
Results Reference
derived
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Efficacy and Safety of 4-aminopyridine on Cognitive Performance and Motor Function of Patients With Multiple Sclerosis
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