Page last updated: 2024-10-21

4-aminopyridine and Fatigue

4-aminopyridine has been researched along with Fatigue in 21 studies

Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli.

Research Excerpts

ExcerptRelevanceReference
"Changes in modified fatigue impact scale (MFIS) score and network RS FC were assessed."7.01Cortico-subcortical functional connectivity modifications in fatigued multiple sclerosis patients treated with fampridine and amantadine. ( Colombo, B; Filippi, M; Martinelli, V; Rocca, MA; Valsasina, P, 2021)
"Modified-release 4-aminopyridine (fampridine-MR) is used in the symptomatic treatment of walking disability in patients with multiple sclerosis (MS)."5.34Effects of modified-release fampridine on upper limb impairment in patients with Multiple Sclerosis. ( Belinda, B; Elise, H; Joanne, D; Leeanne, C; Leonid, C; Marion, S; Richard, M, 2020)
" Search terms included multiple sclerosis, fatigue, medication treatments, amantadine, modafinil, aspirin, acetyl-l-carnitine, pemoline, 4-aminopyridine and randomized controlled trial (RCT)."4.95Pharmacological treatments for fatigue in patients with multiple sclerosis: A systematic review and meta-analysis. ( Deng, XY; Wang, L; Yang, TT; Yu, G, 2017)
"Changes in modified fatigue impact scale (MFIS) score and network RS FC were assessed."3.01Cortico-subcortical functional connectivity modifications in fatigued multiple sclerosis patients treated with fampridine and amantadine. ( Colombo, B; Filippi, M; Martinelli, V; Rocca, MA; Valsasina, P, 2021)
"Thirteen subjects with amyotrophic lateral sclerosis and seven subjects with only a lower motor neuron syndrome."2.76Effects of 3-4 diaminopyridine (DAP) in motor neuron diseases. ( Bertorini, TE; Igarashi, M; Li, YD; Rashed, H; Tolley, EA; Zeno, M, 2011)
"2% of patients presented adverse drug reactions (ADRs) while using moderate doses of 3,4-DAP (20-30 mg daily or up to 80 mg daily for patients with LEMS) for periods of up to 51 months."2.753,4-diaminopyridine safety in clinical practice: an observational, retrospective cohort study. ( Allain, H; Edan, G; Flet, L; Guillard, O; Javaudin, L; Leray, E; Polard, E, 2010)
"Bupropion XL was superior to placebo at endpoint in reducing the IDS-IVR-30 total score (p = ."2.72Extended-release bupropion for patients with major depressive disorder presenting with symptoms of reduced energy, pleasure, and interest: findings from a randomized, double-blind, placebo-controlled study. ( Hampton, KD; Jefferson, JW; Krishen, A; Modell, JG; Nelson, JC; Rush, AJ; VanMeter, SA; Wightman, DS, 2006)
"At the end of the treatment, EDSS, fatigue and depression scores were further evaluated."2.71Fatigue in multiple sclerosis: multidimensional assessment and response to symptomatic treatment. ( Alfonsi, E; Bergamaschi, R; Callieco, R; Candeloro, E; Cosi, V; Romani, A, 2004)

Research

Studies (21)

TimeframeStudies, this research(%)All Research%
pre-19900 (0.00)18.7374
1990's1 (4.76)18.2507
2000's7 (33.33)29.6817
2010's10 (47.62)24.3611
2020's3 (14.29)2.80

Authors

AuthorsStudies
Marion, S1
Leonid, C1
Belinda, B1
Joanne, D1
Elise, H1
Leeanne, C1
Richard, M1
Chiriboga, CA1
Marra, J1
LaMarca, NM1
Young, SD1
Weimer, LH1
Levin, B1
McCabe, B1
Rocca, MA1
Valsasina, P1
Colombo, B1
Martinelli, V1
Filippi, M1
Yang, TT1
Wang, L1
Deng, XY1
Yu, G1
Broicher, SD1
Filli, L1
Geisseler, O1
Germann, N1
Zörner, B1
Brugger, P1
Linnebank, M1
Bakirtzis, C1
Konstantinopoulou, E1
Langdon, DW1
Grigoriadou, E1
Minti, F1
Nikolaidis, I1
Boziki, MK1
Tatsi, T1
Ioannidis, P1
Karapanayiotides, T1
Afrantou, T1
Hadjigeorgiou, G1
Grigoriadis, N1
Foschi, M1
Lugaresi, A1
De Giglio, L1
De Luca, F1
Gurreri, F1
Ferrante, I1
Prosperini, L1
Borriello, G1
Quartuccio, E1
Gasperini, C1
Pozzilli, C3
Allart, E1
Benoit, A1
Blanchard-Dauphin, A1
Tiffreau, V1
Thevenon, A1
Zephir, H1
Outteryck, O1
Lacour, A1
Vermersch, P1
Pavsic, K1
Pelicon, K1
Ledinek, AH1
Sega, S1
Korsen, M1
Kunz, R1
Schminke, U1
Runge, U1
Kohlmann, T1
Dressel, A1
Flet, L1
Polard, E1
Guillard, O1
Leray, E1
Allain, H1
Javaudin, L1
Edan, G1
Bertorini, TE1
Rashed, H1
Zeno, M1
Tolley, EA1
Igarashi, M1
Li, YD1
Mainero, C1
Inghilleri, M1
Pantano, P1
Conte, A1
Lenzi, D1
Frasca, V1
Bozzao, L1
Romani, A1
Bergamaschi, R1
Candeloro, E1
Alfonsi, E1
Callieco, R1
Cosi, V1
Debouverie, M1
Pittion, S1
Boërio, D1
Lefaucheur, JP1
Hogrel, JY1
Créange, A1
Jefferson, JW1
Rush, AJ1
Nelson, JC1
VanMeter, SA1
Krishen, A1
Hampton, KD1
Wightman, DS1
Modell, JG1
Sheean, GL1
Murray, NM1
Rothwell, JC1
Miller, DH1
Thompson, AJ1
Montreuil, M1
Vernay, D1
Rossini, PM1
Pasqualetti, P1
Grasso, MG1
Millefiorini, E1
Graceffa, A1
Carlesimo, GA1
Zibellini, G1
Caltagirone, C1

Clinical Trials (6)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
Observational Study of the Effect of Ozanimod on Fatigue in Multiple Sclerosis Patients[NCT05319093]40 participants (Anticipated)Observational2022-04-30Not yet recruiting
A PILOT STUDY OF INTRAVENOUS, SUBANESTHETIC DOSE OF KETAMINE VS PLACEBO, A CROSSOVER DESIGN, FOR MULTIPLE SCLEROSIS RELATED FATIGUE[NCT06064162]Early Phase 120 participants (Anticipated)Interventional2023-10-31Not yet recruiting
Short and Long Term Fampridine Treatment in Persons With Multiple Sclerosis: Cognitive and Motor Performances[NCT02849782]Phase 489 participants (Actual)Interventional2014-02-04Completed
Efficacy and Safety of 4-aminopyridine on Cognitive Performance and Motor Function of Patients With Multiple Sclerosis. Randomized, Blinded, Placebo-controlled Clinical Trial.[NCT02280096]Phase 224 participants (Actual)Interventional2014-10-31Completed
A Randomised, Double Blinded Cross-over Study Comparing the Efficacy of L-carnitine Versus Placebo in the Treatment of Fatigue in Multiple Sclerosis[NCT01149525]Phase 359 participants (Actual)Interventional2010-06-30Completed
An 8 Week, Multicenter, Randomized, Double-blind, Placebo Controlled Comparison of the Efficacy of Extended Release Bupropion Hydrochloride and Placebo in the Treatment of Adult Outpatients With Major Depressive Disorder With Lethargic Symptoms[NCT00064467]Phase 3268 participants Interventional2003-06-30Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

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). (NCT02280096)
Timeframe: 5-8 minutes

Interventionunits on a scale (seconds) (Mean)
4-aminopyridine68.91
Placebo67.3

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 (NCT02280096)
Timeframe: 10 minutes

Interventionscore on a scale (Mean)
4-aminopirydine4.3
Placebo3.3

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. (NCT02280096)
Timeframe: 15-20 minutes

Interventionscore on a scale (Mean)
4-aminopyridine Treatment4.6
Placebo4.04

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. (NCT02280096)
Timeframe: 7-10 min

Interventioncorrect numbers recalled (Mean)
4-aminopyridine6.1
Placebo5

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). (NCT02280096)
Timeframe: 10-15 minutes

Interventionunits on a scale (seconds) (Mean)
4-aminopyridine208.6
Placebo231.2

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. (NCT02280096)
Timeframe: 10-15 minutes

InterventionCorrect words (Mean)
4-aminopyridine42.09
Placebo35.5

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. (NCT02280096)
Timeframe: 5-10 minutes

Interventionseconds (Mean)
4-aminopyridine15.2
Placebo10.4

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)" (NCT02280096)
Timeframe: 10-15 minutes

Interventionscore on a scale (Mean)
4-aminopyridine19.8
Placebo22.8

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. (NCT02280096)
Timeframe: 8-10 min

,
Interventionseconds (Mean)
Reading speedCount speedAlternation speed
4-aminopirydine2830.560.3
Placebo29.634.258.8

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. (NCT02280096)
Timeframe: 22 weeks

,
InterventionParticipants (Count of Participants)
Number of participants with abnormal lab resultsNumber of participants with abnormal EEG
4-aminopyridine Treatment10
Placebo00

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). (NCT02280096)
Timeframe: 25-30 minutes

,
Interventionseconds (Mean)
Total execution timeTotal problem-solving time
4-aminopyridine296.2363.3
Placebo367.9426.8

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). (NCT02280096)
Timeframe: 25-30 minutes

,
Interventionscore on a scale (Mean)
Total movesCorrect moves
4-aminopyridine42.74
Placebo50.83

Reviews

2 reviews available for 4-aminopyridine and Fatigue

ArticleYear
Pharmacological treatments for fatigue in patients with multiple sclerosis: A systematic review and meta-analysis.
    Journal of the neurological sciences, 2017, Sep-15, Volume: 380

    Topics: 4-Aminopyridine; Amantadine; Central Nervous System Stimulants; Dopamine Agents; Drug Therapy; Fatig

2017
[Pathophysiology and treatment of fatigue in multiple sclerosis].
    Revue neurologique, 2006, Volume: 162, Issue:3

    Topics: 4-Aminopyridine; Acute Disease; Amantadine; Amifampridine; Asthenia; Benzhydryl Compounds; Central N

2006

Trials

12 trials available for 4-aminopyridine and Fatigue

ArticleYear
Effects of modified-release fampridine on upper limb impairment in patients with Multiple Sclerosis.
    Multiple sclerosis and related disorders, 2020, Volume: 40

    Topics: 4-Aminopyridine; Adult; Double-Blind Method; Electrophysiological Phenomena; Fatigue; Female; Humans

2020
Lack of effect on ambulation of dalfampridine-ER (4-AP) treatment in adult SMA patients.
    Neuromuscular disorders : NMD, 2020, Volume: 30, Issue:8

    Topics: 4-Aminopyridine; Adult; Cross-Over Studies; Double-Blind Method; Fatigue; Female; Humans; Male; Midd

2020
Cortico-subcortical functional connectivity modifications in fatigued multiple sclerosis patients treated with fampridine and amantadine.
    European journal of neurology, 2021, Volume: 28, Issue:7

    Topics: 4-Aminopyridine; Amantadine; Brain; Fatigue; Humans; Magnetic Resonance Imaging; Multiple Sclerosis

2021
Positive effects of fampridine on cognition, fatigue and depression in patients with multiple sclerosis over 2 years.
    Journal of neurology, 2018, Volume: 265, Issue:5

    Topics: 4-Aminopyridine; Cognition; Delayed-Action Preparations; Depression; Double-Blind Method; Fatigue; F

2018
Effect of dalfampridine on information processing speed impairment in multiple sclerosis.
    Neurology, 2019, 08-20, Volume: 93, Issue:8

    Topics: 4-Aminopyridine; Adolescent; Adult; Aged; Cognition Disorders; Double-Blind Method; Fatigue; Female;

2019
Short-term impact of fampridine on motor and cognitive functions, mood and quality of life among multiple sclerosis patients.
    Clinical neurology and neurosurgery, 2015, Volume: 139

    Topics: 4-Aminopyridine; Activities of Daily Living; Adult; Affect; Aged; Cognition; Depression; Exercise Te

2015
3,4-diaminopyridine safety in clinical practice: an observational, retrospective cohort study.
    Journal of neurology, 2010, Volume: 257, Issue:6

    Topics: 4-Aminopyridine; Adolescent; Adult; Aged; Amifampridine; Child; Cohort Studies; Dyskinesias; Fatigue

2010
Effects of 3-4 diaminopyridine (DAP) in motor neuron diseases.
    Journal of clinical neuromuscular disease, 2011, Volume: 12, Issue:3

    Topics: 4-Aminopyridine; Adult; Aged; Aged, 80 and over; Amifampridine; Cross-Over Studies; Double-Blind Met

2011
Enhanced brain motor activity in patients with MS after a single dose of 3,4-diaminopyridine.
    Neurology, 2004, Jun-08, Volume: 62, Issue:11

    Topics: 4-Aminopyridine; Adult; Amifampridine; Axons; Cross-Over Studies; Double-Blind Method; Electromyogra

2004
Fatigue in multiple sclerosis: multidimensional assessment and response to symptomatic treatment.
    Multiple sclerosis (Houndmills, Basingstoke, England), 2004, Volume: 10, Issue:4

    Topics: 4-Aminopyridine; Adult; Antidepressive Agents, Second-Generation; Cognition; Depression; Disability

2004
Extended-release bupropion for patients with major depressive disorder presenting with symptoms of reduced energy, pleasure, and interest: findings from a randomized, double-blind, placebo-controlled study.
    The Journal of clinical psychiatry, 2006, Volume: 67, Issue:6

    Topics: 4-Aminopyridine; Adult; Aged; Antidepressive Agents, Second-Generation; Anxiety; Bupropion; Depressi

2006
Fatigue in progressive multiple sclerosis: results of a randomized, double-blind, placebo-controlled, crossover trial of oral 4-aminopyridine.
    Multiple sclerosis (Houndmills, Basingstoke, England), 2001, Volume: 7, Issue:6

    Topics: 4-Aminopyridine; Administration, Oral; Adult; Cognition; Cross-Over Studies; Disability Evaluation;

2001

Other Studies

7 other studies available for 4-aminopyridine and Fatigue

ArticleYear
Long-term effects of prolonged-release fampridine in cognitive function, fatigue, mood and quality of life of MS patients: The IGNITE study.
    Journal of the neurological sciences, 2018, 12-15, Volume: 395

    Topics: 4-Aminopyridine; Affect; Cognition; Delayed-Action Preparations; Disability Evaluation; Fatigue; Fem

2018
Evaluating dalfampridine for the treatment of relapsing-remitting multiple sclerosis: does it add to the treatment armamentarium?
    Expert opinion on pharmacotherapy, 2019, Volume: 20, Issue:11

    Topics: 4-Aminopyridine; Clinical Trials as Topic; Cognitive Dysfunction; Cost-Benefit Analysis; Databases,

2019
Sustained-released fampridine in multiple sclerosis: effects on gait parameters, arm function, fatigue, and quality of life.
    Journal of neurology, 2015, Volume: 262, Issue:8

    Topics: 4-Aminopyridine; Adult; Aged; Exercise Test; Fatigue; Female; Follow-Up Studies; Gait; Hand; Humans;

2015
Dalfampridine effects on cognition, fatigue, and dexterity.
    Brain and behavior, 2017, Volume: 7, Issue:1

    Topics: 4-Aminopyridine; Adult; Cognitive Dysfunction; Depression; Evoked Potentials, Visual; Fatigue; Femal

2017
[Fatigue and episodic exhaustion as a feature of multiple sclerosis].
    Revue neurologique, 2006, Volume: 162, Issue:3

    Topics: 4-Aminopyridine; Amantadine; Amifampridine; Benzhydryl Compounds; Fatigue; Humans; Hypnotics and Sed

2006
An open-labelled clinical and electrophysiological study of 3,4 diaminopyridine in the treatment of fatigue in multiple sclerosis.
    Brain : a journal of neurology, 1998, Volume: 121 ( Pt 5)

    Topics: 4-Aminopyridine; Adult; Amifampridine; Analysis of Variance; Case-Control Studies; Electromyography;

1998
[Workshop on fatigue and multiple sclerosis].
    Revue neurologique, 2000, Volume: 156, Issue:11

    Topics: 4-Aminopyridine; Fatigue; Humans; Multiple Sclerosis; Potassium Channel Blockers; Psychotherapy

2000