Cross-over Study on the Influence of Fampridine on Working Memory in Mild Depression

Phase 2

Not yet recruiting

• Conditions: Working Memory; Mild Depression
• Interventions: Other: Placebo; Drug: Fampridine SR

• Registration Number: NCT06751784
• Lead Sponsor: University of Basel

Brief Summary

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 depression

Detailed Description

Randomized placebo-controlled phase II cross-over study on the influence of fampridine on working memory in mild depression The primary objective of this study is to evaluate if fampridine improves working memory in mild 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, 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 Timeline

• Study First Submitted: 2024-12-20
• Study First Submitted QC: 2024-12-20
• Study First Posted: 2024-12-30
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-06
• Last Update Posted: 2025-01-08
• Study Start: 2025-04
• Primary Completion: 2026-07
• Study Completion: 2026-07

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 38

Inclusion Criteria

• Male or female
• Major depressive episode confirmed by the Mini-International Neuropsychiatric Interview. Currently mild (MADRS: 7-19).
• Normotensive (BP: 90/60mmHg - 140/90mmHg). Sufficiently treated hypertensive subjects will be included.
• BMI: 19 - 34,9 kg/m2
• Age: 18 - 30 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)
• MADRS item 10 > 0 (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 (>5 cigarettes per day)
• 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
• 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Other intervention	Placebo	15 Identically looking placebo tablets consisting of widely identical additives formulated for oral administration.
Intervention	Fampridine SR	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.

Primary Outcome Measures

Name	Time	Method
High-load working memory performance	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 Outcome Measures

Name	Time	Method
Reaction time (for correct 3-back responses).	Before first intake of study medication and after last intake of study medication of the 7.5-days-treatment periods	letter n-back task
Performance in a 0-back task (d') as a measure of attention.	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.
Working memory assessed by the digit span task (backward and forward), a subtest of the WIE	Before first intake of study medication and after last intake of study medication of a 7.5-days-treatment periods	Total scores for digit span forward and backward will be calculated as described in the manual of the WIE. Parallel versions (different digit sequences) are used for the four test days.; Digit span task forward and backward, a subtest of the "Wechsler Intelligenztest für Erwachsene" . Total scores for digit span forward and backward will be calculated as described in the manual of the WIE. Parallel versions (different sequences) are used for the four test days.
Verbal episodic memory performance measured by immediate and delayed word-list recall task	Before first intake of study medication and after last intake of study medication of a 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 rcall). 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 out of the following test are used: Verbaler Lern-und Merkfähigkeitstest, VLMT
Lexical ability measured by phonemic fluency test (S-words)	Before first intake of study medication and after last intake of study medication of a 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.
Planning and Problem solving, key aspects of executive functioningwill be measured with the "Tower of London" (ToL) test	Before first intake of study medication and after last intake of study medication of a 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. Parallel version will be used for the four test days.
Cognitive Flexibility will be assessed through the "Intra-Extra Dimensional Set Shifting (IED)" task	Before first intake of study medication and after last intake of study medication of a 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.Parallel version will be used for the four test days.
The severity of depressive symptoms will be assessed using MADRS (external rating).	Before first intake of study medication and after last intake of study medication of a 7.5-days-treatment periods	The MADRS consists of 10 items assessing subjects' apparent and reported sadness, 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 ten items, ranging between 0 and 60 (higher scores indicate increased severity).

Trial Locations

Locations (1)

University of Basel, Reserach Cluster Molecular and Cognitive Neurosciences; 🇨🇭 Basel, BS, Switzerland