Influence of Fampridine on Working Memory in Healthy Young Subjects (FamH)

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 acute effects on working memory of 10 mg fampridine SR as well as the effects after repeated administration of 10 mg twice daily (3.5 days).

The hypothesis ist that fampridine improves working memory performance.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Annette Harings-Kaim, MD; Phone Number: +41 61 207 0251; Email: annette.harings@unibas.ch

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: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• male or female
• generally healthy
• normotensive (BP between 90/60mmHg and 140/90mmHg)
• BMI between 19 and 29,9 kg/m2
• aged between 18 and 30 years
• fluent German-speaking
• IC as documented by signature
• at least double vaccination against Covid-19

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 and substrates (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)
• bradycardia > 50/min during clinical examination
• 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
• experiencing a syncope during basal rMT measuring
• metal in the brain, skull or elsewhere in the body (e.g., splinters, fragments, clips, etc.)
• implanted neurostimulator (e.g., DBS, epidural/subdural, VNS)
• cardiac pacemaker or intracardiac lines
• medication infusion device
• piercings, pivot teeth (retainers are no exclusion criterion)
• tattoos (head area) less than 3 months old or older than 20 years
• condition after neurosurgery
• hearing problems or tinnitus
• not able to sit still due to tremor, tics, itching
• history of repeated syncope
• head trauma diagnosed as concussion or associated with loss of consciousness
• diagnosis of epilepsy, or a convulsion or a seizure in the past of the participant or his family
• TMS in the past showing problems
• MRI in the past showing problems
• surgical procedures to spinal cord
• spinal or ventricular derivations

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Fampridine SR; Active study medication consists of 7 tablets of fampridine SR 10 mg formulated for oral administration taken in the morning and evening 12 h apart without food. Tablets must be administered whole. There will be a washout period of at least 8 days equaling over 30 half-lives of the active substance fampridine (t½ = 6 h) between experimental and control intervention and up to 82 days depending on the individual scheduling of each subject.	Drug: Fampridine SR; Fampridine SR is an inhibitor of voltage gated potassium 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 widely 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
High-load working-memory performance after repeated administrations (3.5 days)	It will be used the letter n-back task (Heck, Fastenrath et al. 2014)) which includes a 3-back task assessing working memory. The 3-back task requires participants to respond to a letter repeat with two intervening letters (for example, S-m-b-s-g…). Performance will be quantified with the d' measure controlling for false positives. It will be used parallel versions (different sequences) for the four test days. Primary outcome will be performance after repeated intake of study medication.	test days 2 and 4 (end of treatment periods; 4 hours after last intake of fampridine SR) to assess changes between the Verum and Placebo condition

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
High-load working-memory performance after acute administration	It will be used the letter n-back task (Heck, Fastenrath et al. 2014)) which includes a 3-back task assessing working memory. The 3-back task requires participants to respond to a letter repeat with two intervening letters (for example, S-m-b-s-g…). Performance will be quantified with the d' measure controlling for false positives. It will be administered parallel versions (different sequences) for the four test days. Primary outcome will be performance after repeated intake of study medication.	test days 1 and 3 (beginning of treatment periods; 4 hours after first intake of fampridine SR) to assess differences between the Verum and Placebo condition
Reaction time after acute and repeated intake	Reaction time for correct answers in the 3-back (d') task (see outcomes 1 and 2)	test days 1 and 3 (beginning of treatment periods; 4 hours after first intake of fampridine SR) to assess differences between the Verum and Placebo condition
Attention after acute and repeated administration	Performance in a 0-back task (d' measure controlled). It will be used parallel versions (different sequences) for the four test days.	first and last day of treatment periods (each 4 hours after intake in the morning); to assess differences between the Verum and Placebo condition
Symbol Digit Modalities Test (SDMT; Smith 1973) after acute and repeated intake	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 pseudo-randomized 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 (max. 110). The administration of SDMT will be preceded by a learning sequence at both timepoints. It will be used parallel versions for all test days.	first and last day of treatment periods (each 4 hours after intake in the morning); to assess differences between the Verum and Placebo condition
Fluid intelligence (Gf): Bochumer Matrizentest (BOMAT)	Bochumer Matrizentest (BOMAT - advanced -short; Hossiep/Turck/Hasella, 2001, 1st edition), matrix reasoning. It will be administered the BOMAT to measure fluid intelligence (Gf) consisting of 20 items (maximum 20 correct answers possible). Parallel versions will be used for the four test days. It will be used a time-limited version according to Jaeggi (Jaeggi 2010).	first and last day of treatment periods (each 4 hours after intake in the morning); to assess differences between the Verum and Placebo condition
Working-memory: Digit Span Task	Working memory will be also assessed with the 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. Parallel version will be used for the four test days.	first and last day of treatment periods (each 4 hours after intake in the morning); to assess differences between the Verum and Placebo condition
Resting motor threshold (rMT)	The resting motor threshold (rMT) will be measured by transcranial magnetic stimulation (TMS). rMT will be determined by measuring the motor evoked potential (MEP) in the abductor digiti minimi according to Rossini (2001). rMT will be defined as the lowest stimulation intensity by stimulating the primary motor cortex of the left or right hemisphere required to induce an MEP in the abductor digiti minimi of the dominant hand in at least 5 out of 10 trials.	test days 2 and 4 (last day of treatment periods; approx. 5 hours after last intake of fampridine SR) 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

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 1, 2021
• Primary Completion (ACTUAL): January 26, 2023
• Study Completion (ACTUAL): January 26, 2023

Study Registration Dates

• First Submitted: November 24, 2020
• First Submitted That Met QC Criteria: December 2, 2020
• First Posted (ACTUAL): December 3, 2020

Study Record Updates

• Last Update Posted (ACTUAL): February 6, 2023
• Last Update Submitted That Met QC Criteria: February 3, 2023
• Last Verified: February 1, 2023

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: 2020-02828

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All IPD (de-identified) that underline 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 underline 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. Request will be reviewed by the team of the principal investigator.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; 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