Influence of Fampridine on Working Memory in Healthy Subjects (Fampyr_2020)

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Working Memory
• Intervention / Treatment: Drug: Placebo; Drug: Fampridine SR

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Switzerland
  • BS
    • Basel, BS, Switzerland, 4055
      • University of Basel, Transfaculty Research Platform

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 30 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fampridine SR; 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; 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).
Placebo Comparator: Placebo; Identically looking placebo tablets consisting of the identical additives formulated for oral administration.	Drug: Placebo; no active component

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Prof. Dominique de Quervain, MD
• Collaborators: University Hospital, Basel, Switzerland; Clinical Trial Unit, University Hospital Basel, Switzerland
• Investigators: Study Chair: Dominique de Quervain, Prof, University of Basel, Transfaculty Research Platform; Study Chair: Andreas Papassotiropoulos, Prof, University of Basel, Transfacutly Research Platform

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2020
• Primary Completion (Anticipated): December 31, 2021
• Study Completion (Anticipated): December 31, 2021

Study Registration Dates

• First Submitted: August 11, 2020
• First Submitted That Met QC Criteria: August 13, 2020
• First Posted (Actual): August 18, 2020

Study Record Updates

• Last Update Posted (Actual): October 19, 2020
• Last Update Submitted That Met QC Criteria: October 13, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Potassium Channel Blockers; 4-Aminopyridine
• Other Study ID Numbers: 2020-01626

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: All IPD (de-identified) that underlie results in a publication will be shared upon reasonable request.
• IPD Sharing Time Frame: IPD will be available after publication, study protocol (including statistical analysis plan) will be made available before start of the study.
• IPD Sharing Access Criteria: All IPD (de-identified) that underlie results in a publication will be shared upon reasonable request for scientific purposes. A reasonable request consists of a short description of the scientific purpose. Requests will be reviewed by the team of the principle investigator.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No