Randomized Placebo-controlled Phase II Cross-over Study on the Influence of Fampridine on Working Memory in Mild to Moderate Depression
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 38
- 试验地点
- 1
- 主要终点
- High-load working memory performance.
研究概览
简要总结
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
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Fampridine SR (Drug)
Other intervention
15 Identically looking placebo tablets consisting of widely identical additives formulated for oral administration.
干预措施: Placebo (Other)
结局指标
主要结局
High-load working memory performance.
时间窗: 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.
次要结局
- Adaptive verbal working memory capacity test (SPAN) backward.(Before first intake of study medication and after last intake of study medication of the 7.5-days-treatment periods)
- 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)
- Lexical ability measured using a phonemic verbal fluency task (S-words).(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.(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.(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.(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.(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.(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).(Before first intake of study medication and after last intake of study medication of the 7.5-days-treatment periods)
研究者
Christiane Gerhards
Medical Doctor
University of Basel