Cross-over Study on the Influence of Fampridine on Working Memory in Mild to Moderate Depression (FamD_2025)

Randomized Placebo-controlled Phase II Cross-over Study on the Influence of Fampridine on Working Memory in Mild to Moderate Depression

Cognitive deficits, including working memory deficits, are often present in depression and there are currently no effective pharmacological treatments targeting working memory deficits. Papassotiropoulos et al. (2024) has recently demonstrated that fampridine, a potassium channel blocker, can enhance working memory in healthy individuals with lower baseline performance, suggesting it may hold potential for addressing cognitive deficits in clinical populations. The primary aim of this study is to evaluate whether fampridine improves working memory performance in mild to moderate depression

Study Overview

• Status: Recruiting
• Conditions: Working Memory; Mild to Moderate Depression
• Intervention / Treatment: Drug: Fampridine SR; Other: Placebo

Detailed Description

Randomized placebo-controlled phase II cross-over study on the influence of fampridine on working memory in mild to moderate depression The primary objective of this study is to evaluate if fampridine improves working memory in mild to moderate depression. It will also be assessed whether baseline working memory performance or subjective working memory deficits moderate the drug's effect.

The secondary objectives are to assess the influence of fampridine on different working memory functions, attention, cognitive flexibility, affective working memory and mood.

Intervention:Twice daily oral administration of 10 mg fampridine (Fampyra®) for 7.5 days with a wash-out period of at least 6.5 days Control intervention:Twice daily oral administration of placebo for 7.5 days Study population:Total of 38 participants.

• Study Type: Interventional
• Enrollment (Estimated): 38
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Christiane Gerhards, MD; Phone Number: +41 61 207 0244; Email: christiane.gerhards@unibas.ch

Study Locations

• Switzerland
  • Canton of Basel-City
    • Basel, Canton of Basel-City, Switzerland, 4055
      • Recruiting
      • University of Basel, Reserach Cluster Molecular and Cognitive Neurosciences
      • Contact: Dominique de Quervain, Prof.; Phone Number: +41 61 207 02 37; Email: dominique.dequervain@unibas.ch
      • Contact: Andreas Papassotiropoulos, Prof; Phone Number: +41 61 207 05 88; Email: andreas.paps@unibas.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female
• Major depressive episode confirmed by the Mini-DIPS. Currently mild to moderate (MADRS: 7-30).
• Normotensive (BP: 90/60mmHg - 140/90mmHg). Sufficiently treated hypertensive subjects will be included.
• BMI: 19 - 34,9 kg/m2
• Age: 18 - 55 years
• Fluent in German
• IC 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
• Treatment with OCT 2 inhibitors and -substrates (e.g. cimetidine, propranolol)
• Treatment with antidepressants or antipsychotics within the last 3 months and throughout the study period
• Current intake of psychoactive drugs (e.g. benzodiazepines, antidepressants, neuroleptics).
• Other acute or chronic psychiatric disorder (e.g. psychosis, somatoform disorder, alcohol or drug abuse disorder)
• Cognitive impairment (MoCA score < 25)
• MADRS item 10 > 1 (suicidal tendency)
• Risk of lowered seizure threshold (due to e.g. sleep deprivation, withdrawal of alcohol after alcohol abuse, hyponatraemia)
• History of seizures
• Acute cerebrovascular condition
• Acute renal failure or severe renal insufficiency (creatinine clearance < 30 ml/min per 1.73 m2)
• Bradycardia < 50/min during clinical examination.
• 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
• Severe somatic or neurological comorbidities
• Smoking including all nicotine containing smoking systems and devices (>10 cigarettes/units per day). Failure to withstand a test day without craving, due to regular consummation patterns.
• Pregnancy or breast feeding. Intention to become pregnant during the study participation.
• Known or suspected non-compliance
• 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
• Enrolment of the investigator, his/her family members, employees and other dependent persons

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
Active Comparator: Intervention; Experimental: Fampridin SR Active study medication consists of 15 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 6.5 days equaling over 20 half-lives of the active substance fampridine (t½ = 6 h) between experimental and control intervention and up to 28 days depending on the individual scheduling of each subject.	Drug: Fampridine SR; Active study medication consists of 15 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.
Placebo Comparator: Other intervention; 15 Identically looking placebo tablets consisting of widely identical additives formulated for oral administration.	Other: Placebo; no active substance

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
High-load working memory performance.	Letter n-back task 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. Parallel versions (different sequences) are used for the four test days.	Before first intake of study medication and after last intake of study medication of the 7.5-days-treatment periods

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reaction time (for correct 3-back responses).	letter n-back task	Before first intake of study medication and after last intake of study medication of the 7.5-days-treatment periods
Performance in a 0-back task (d') as a measure of attention.	Letter n-back task.Parallel versions (different sequences) are used for the four test days.	Before first intake of study medication and after last intake of study medication of the 7.5-days-treatment periods
Adaptive verbal working memory capacity test (SPAN) backward.	The SPAN is a computer-based, adaptively administered test based on item response theory (Rasch model; Rasch, 1980). In the study, test form S2 (backward digit span) is used, which captures both storage capacity and executive functions (Baddeley, 2010). Adaptive administration allows for precise, efficient, and individually tailored assessment while minimizing floor and ceiling effects. Test scoring is based on the estimation of a continuous person parameter (θ) using weighted maximum likelihood (Warm, 1989). This parameter reflects the individual's latent working memory ability and is additionally converted into a digit span score with decimal precision, allowing for nuanced interpretation (Gignac & Weiss, 2015).	Before first intake of study medication and after last intake of study medication of the 7.5-days-treatment periods
Verbal episodic memory performance measured by immediate and delayed word-list recall task.	In this test a list of 15 selected words will be presented to the participants with a rate of one word per two seconds and the participant should recall the words immediately in writing (immediate recall). Around 15 minutes later the participants are asked to recall the words again (short delay). Number of correct words recalled in each stage is considered as the participant's immediate and delayed recall score respectively. The four 15-words wordlists (A-D) out of the following test are used: Verbaler Lern-und Merkfähigkeitstest, VLMT	Before first intake of study medication and after last intake of study medication of the 7.5-days-treatment periods
Lexical ability measured using a phonemic verbal fluency task (S-words).	Adapted from a subtest of the Regensburger Wortflüssigkeits-Test (RWT). In this task participants should name orally as many words as possible initiating with a special letter in one minute (e.g. Mary, Milk, Mouse, etc. for the letter M) the number of unique meaningful words will be considered as the participant's score.Different letters (B, K, P, M) are used for each test day.	Before first intake of study medication and after last intake of study medication of the 7.5-days-treatment periods
Planning and Problem solving, key aspects of executive functioningwill be measured with the "Tower of London" (ToL) test.	In this test, participants will be tasked to rearrange colour balls to match a target arrangement in as few moves as possible. The raw score for planning ability (number of correctly solved trials with the minimum number of ball placements) is consider as the participants score. Parallel version will be used for the four test days.	Before first intake of study medication and after last intake of study medication of the 7.5-days-treatment periods
Cognitive Flexibility will be assessed through the "Intra-Extra Dimensional Set Shifting (IED)" task.	Participants are asked to use the given feedback to work out a rule that determines which stimulus (shapes and lines in different combinations) is correct. After six correct responses, the stimuli and/or rule changes. The shifts in rule are initially intra-dimensional and then later extra-dimensional. The highest reached level is considered as the participant's score. Parallel version will be used for the four test days.	Before first intake of study medication and after last intake of study medication of the 7.5-days-treatment periods
The severity of depressive symptoms will be assessed using MADRS-s (self-rating).	The MADRS-s consists of 9 items assessing subjects' mood, inner tension, sleep, appetite, ability to concentrate, initiative, emotional involvement, pessimism and zest for life. Each item is scored between 0 and 6. The total score is calculated by summing the answers of the 9 items, ranging between 0 and 54 (higher scores indicate increased severity).	Before first intake of study medication and after last intake of study medication of the 7.5-days-treatment periods
The affective working memory will be assessed using an emotioanl 2-back.	The task follows a classic N-back paradigm with two conditions: 0-back and 2-back. Emotional faces (happy, sad, neutral; male/female) from the Karolinska Directed Emotional Faces set (Lundqvist et al., 1998) are presented for 1500 ms with a 1350 ms inter-stimulus interval. Participants indicate whether each stimulus is a "hit" or "non-hit," based on the current stimulus (0-back) or compared to the stimulus two trials prior (2-back).	Before first intake of study medication and after last intake of study medication of the 7.5-days-treatment periods

Collaborators and Investigators

• Sponsor: University of Basel
• Collaborators: Clinical Trial Unit, University Hospital Basel, Switzerland
• Investigators: Study Chair: Dominique de Quervain, Prof. MD, Research Cluster Molecular and Cognitive Neurosciences; Study Chair: Andreas Papassotiropoulos, Prof.MD, Research Cluster Molecular and Cognitive Neurosciences; Study Chair: Annette Bruehl, Prof.MD, Zentrum für Affektive -, Stress- und Schlafstörungen & Zentrum für Alterspsychiatrie UPK Basel

Study record dates

Study Major Dates

• Study Start (Actual): May 22, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: December 20, 2024
• First Submitted That Met QC Criteria: December 20, 2024
• First Posted (Actual): December 30, 2024

Study Record Updates

• Last Update Posted (Actual): December 12, 2025
• Last Update Submitted That Met QC Criteria: December 4, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Behavioral Symptoms; Mood Disorders; Depression; Depressive Disorder; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Amines; Aminopyridines; 4-Aminopyridine
• Other Study ID Numbers: 2024-02355

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: PD 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
• product manufactured in and exported from the U.S.: No