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NCT Number: NCT06751784

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

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Key information

Conditions

Working Memory Mild to Moderate Depression

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Fampridine SR

Drug

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

Other

no active substance

Primary outcomes

  1. High-load working memory performance.

    Time frame: Before first intake of study medication and after last intake of study medication of the 7.5-days-treatment periods

    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.

Secondary outcomes

  1. Reaction time (for correct 3-back responses).

    Time frame: Before first intake of study medication and after last intake of study medication of the 7.5-days-treatment periods

    letter n-back task

  2. Performance in a 0-back task (d') as a measure of attention.

    Time frame: Before first intake of study medication and after last intake of study medication of the 7.5-days-treatment periods

    Letter n-back task.Parallel versions (different sequences) are used for the four test days.

  3. Adaptive verbal working memory capacity test (SPAN) backward.

    Time frame: Before first intake of study medication and after last intake of study medication of the 7.5-days-treatment periods

    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).

  4. Verbal episodic memory performance measured by immediate and delayed word-list recall task.

    Time frame: Before first intake of study medication and after last intake of study medication of the 7.5-days-treatment periods

    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

  5. Lexical ability measured using a phonemic verbal fluency task (S-words).

    Time frame: Before first intake of study medication and after last intake of study medication of the 7.5-days-treatment periods

    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.

  6. Planning and Problem solving, key aspects of executive functioningwill be measured with the "Tower of London" (ToL) test.

    Time frame: Before first intake of study medication and after last intake of study medication of the 7.5-days-treatment periods

    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.

  7. Cognitive Flexibility will be assessed through the "Intra-Extra Dimensional Set Shifting (IED)" task.

    Time frame: Before first intake of study medication and after last intake of study medication of the 7.5-days-treatment periods

    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.

  8. The severity of depressive symptoms will be assessed using MADRS-s (self-rating).

    Time frame: Before first intake of study medication and after last intake of study medication of the 7.5-days-treatment periods

    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).

  9. The affective working memory will be assessed using an emotioanl 2-back.

    Time frame: Before first intake of study medication and after last intake of study medication of the 7.5-days-treatment periods

    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).

Study contacts

Contact information is provided by the study sponsor or research team.

Christiane Gerhards, MD

CONTACT

[email protected]

+41 61 207 0244

Sponsors and collaborators

Lead sponsor

University of Basel

Other

Collaborators

  • Clinical Trial Unit, University Hospital Basel, Switzerland

Registry information

Official study title

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

Acronym: FamD_2025

Important dates

Study start
2025
Primary completion
2026
Study completion
2026
First posted
Dec 30, 2024
Registry last updated
Dec 12, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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