Influence of Fampridine on Working Memory in Healthy Subjects

Study Overview
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Brief Summary
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Proof-of-concept study on the effects of 10 mg fampridine (oral administration) on working memory in healthy participants. The hypotheses is that fampridine improves working memory performance.

Official Title
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Randomized Placebo-controlled Phase II Cross-over Study on the Influence of Fampridine on Working Memory in Healthy Subjects

Conditions
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Working Memory

Intervention / Treatment
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* Drug: Fampridine SR
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: male or female generally healthy normotensive (BP between 90/60 mmHg and 140/90 mmHg) BMI between 19 and 29,9 kg/m2 aged between 18 and 30 years fluent German-speaking Informed consent as documented by signature Exclusion Criteria: contraindications to the class of drugs under study, e.g. known hypersensitivity or allergy to 4-aminopyridine use of potassium channel blockers within the last 3 months concomitant treatment with OCT 2 inhibitors (e.g. cimetidine, propranolol) acute or chronic psychiatric disorder (e.g. major depression, psychoses, somatoform disorder, suicidal tendency) acute cerebrovascular condition history of seizures risk of lowered seizure threshold (due to e.g. sleep deprivation, withdrawal of alcohol after alcohol abuse) renal impairment history of malignant cancers walking problems (e.g. due to dizziness) other clinically significant concomitant disease states (e.g. hepatic dysfunction, cardiovascular disease, diabetes, asthma) clinically significant laboratory or ECG abnormality that could be a safety issue in the study known or suspected non-compliance drug or alcohol abuse inability to follow the procedures of the study, e.g. due to language or psychological problems of the participant participation in another study with an investigational drug within the 30 days preceding and during the present study prior participation (less than two years ago) in a study investigating working memory (notably the n-back task) enrolment of the investigator, his/her family members, employees and other dependent persons smoking (>3 cigarettes per day) intake of psychoactive drugs (e.g. benzodiazepines, antidepressants, neuroleptics) pregnancy or breast feeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fampridine SR<br>Single oral administration of a tablet fampridine (10 mg) formulated for oral administration taken once in the morning without food. Tablets must be administered whole. The single intake is followed by a washout period of at least 7 days equalling over 40 half-lives of the active substance fampridine (t½ = 3.61 h) between experimental and control intervention. | Drug: Fampridine SR<br>* Fampridine is an inhibitor of voltage-gated potassium (Kv) channels and is approved in Switzerland for treatment of gait problems in patients with Multiple Sclerosis (MS).<br>|
| Placebo Comparator: Placebo<br>Identically looking placebo tablets consisting of the identical additives formulated for oral administration. | Drug: Placebo<br>* no active component<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Medium-load working memory performance | Accuracy as assessed by a letter n-back task (Papassotiropoulos, Henke et al. 2011) with the levels 0-back and 2-back. This test includes a 2-back task assessing working memory and a 0-back task ('x-target' task) measuring concentration. The 2-back task requires participants to respond to a letter repeat with one intervening letter (for example, S-m-s-g…). The 'x-target' task requires participants to respond to the occurrence of the letter 'x' in a sequence of letters (for example, N-l-X-g…). Accuracy (i.e. correct 2-back responses minus correct 0-back responses) will be calculated. | test day 1 and 2, each 4 hours after intake of study medication to assess differences between the Verum and Placebo condition | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reaction time | Reaction time for correct 2-back responses minus correct 0-back responses. | test day 1 and 2 each 4 hours after intake of study medication to assess differences between the Verum and Placebo condition | 
| N-back with a 3-back condition | N-back with a 3-back condition, which is more demanding than the 2-back condition. Accuracy (3-back minus 0-back) will be calculated. | test day 1 and 2 each 4 hours after intake of study medication to assess differences between the Verum and Placebo condition | 
| Symbol Digit Modalities Test, SDMT | Symbol Digit Modalities Test, SDMT (Smith 2013, 13th edition), a processing speed test. The test consists of the presentation of a series of 9 symbols, each of them is paired with a single digit, labeled 1-9, in a key at the top of a sheet. The remainder of the page has a pseudorandomized sequence of the symbols and the participant must respond with the digit associated with each of these as quickly as possible. The score is the number of correct answers in 90 seconds. The administration of SDMT will be preceded by a learning sequence at both timepoints. A parallel version will be used for the second test day. | test day 1 and 2 each 4 hours after intake of study medication to assess differences between the Verum and Placebo condition | 
| Bochumer Matrizentest (BOMAT - advanced -short) | Bochumer Matrizentest (BOMAT - advanced -short; Hossiep/Turck/Hasella, 2001, 1st edition), matrix reasoning. The BOMAT will be administered to measure fluid intelligence (Gf) consisting of 29 items. A time-limited version will be used according to Jaeggi (Jaeggi 2010). The total score is calculated by summing the correct solutions, ranging between 0 to 29. A parallel version will be used for the second test day. | test day 1 and 2 each 4 hours after intake of study medication to assess differences between the Verum and Placebo condition | 
| Digit Span Task | Digit span task, a subtest of the Wechsler Intelligenztest für Erwachsene (WIE;von Aster 2006). Total scores for digit span forward and backward will be calculated as described in the manual of the WIE. A parallel version will be used for the second test day. | test day 1 and 2 each 4 hours after intake of study medication to assess differences between the Verum and Placebo condition |