Clinical trial NCT06751784: Cross-over Study on the Influence of Fampridine on Working Memory in Mild Depression
Official title: Randomized Placebo-controlled Phase II Cross-over Study on the Influence of Fampridine on Working Memory in Mild Depression
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Working Memory
Mild Depression
Lead sponsor: University of Basel
Sponsor class: OTHER
Collaborators: name: Clinical Trial Unit, University Hospital Basel, Switzerland
First posted: 2024-12-30
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Maximum age (years): 30
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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, 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.

Eligibility criteria: Inclusion Criteria:

* Male or female
* Major depressive episode confirmed by the Mini-DIPS. 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

Primary outcomes:
measure: High-load working memory performance
timeFrame: Before first intake of study medication and after last intake of study medication of the 7.5-days-treatment periods
Secondary outcomes:
measure: Reaction time (for correct 3-back responses).
timeFrame: Before first intake of study medication and after last intake of study medication of the 7.5-days-treatment periods
measure: Performance in a 0-back task (d') as a measure of attention.
timeFrame: Before first intake of study medication and after last intake of study medication of the 7.5-days-treatment periods
measure: Working memory assessed by the digit span task (backward and forward), a subtest of the WIE
timeFrame: Before first intake of study medication and after last intake of study medication of a 7.5-days-treatment periods
measure: Verbal episodic memory performance measured by immediate and delayed word-list recall task
timeFrame: Before first intake of study medication and after last intake of study medication of a 7.5-days-treatment periods
measure: Lexical ability measured by phonemic fluency test (S-words)
timeFrame: Before first intake of study medication and after last intake of study medication of a 7.5-days-treatment periods
measure: Planning and Problem solving, key aspects of executive functioningwill be measured with the "Tower of London" (ToL) test
timeFrame: Before first intake of study medication and after last intake of study medication of a 7.5-days-treatment periods
measure: Cognitive Flexibility will be assessed through the "Intra-Extra Dimensional Set Shifting (IED)" task
timeFrame: Before first intake of study medication and after last intake of study medication of a 7.5-days-treatment periods
measure: The severity of depressive symptoms will be assessed using MADRS (self assessment).
timeFrame: Before first intake of study medication and after last intake of study medication of a 7.5-days-treatment periods
measure: The affective working memory will be assessed using an emotioanl 2-back
timeFrame: Before first intake of study medication and after last intake of study medication of the 7.5-days-treatment periods
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University of Basel, Reserach Cluster Molecular and Cognitive Neurosciences
state: BS
Study officials:
affiliation: Research Cluster Molecular and Cognitive Neurosciences
name: Dominique de Quervain, Prof. MD
role: STUDY_CHAIR
affiliation: Research Cluster Molecular and Cognitive Neurosciences
name: Andreas Papassotiropoulos, Prof.MD
role: STUDY_CHAIR
affiliation: Zentrum für Affektive -, Stress- und Schlafstörungen & Zentrum für Alterspsychiatrie UPK Basel
name: Annette Bruehl, Prof.MD
role: STUDY_CHAIR
References: