Randomised, Double-Blind, Placebo-Controlled, Crossover Study Investigating the Role of Potassium Channels in Working Memory Impairments of Chronic Cocaine Users
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- Global Working Memory Performance
研究概览
简要总结
The study aims to address the neurobiological basis of cognitive impairments in chronic cocaine users by investigating the potential impact of an acute potassium channel blockade on working memory performance and other cognitive functions.
详细描述
Chronic cocaine use is associated with impairments in cognitive functions, particularly in working memory, which are thought to contribute to the persistence of addictive behaviors and high relapse rates. Despite the clinical relevance of these cognitive deficits, the underlying neuropharmacological mechanisms remain insufficiently understood.
Preclinical and clinical evidence suggests that potassium channels may play an important role in the regulation of neuronal excitability and cognitive processes, including working memory. However, their contribution to cognitive impairments in individuals with cocaine use disorder has not yet been systematically investigated in humans.
The present study aims to investigate the role of potassium channel modulation in working memory performance in individuals with chronic cocaine use. The study addresses the following key research questions: (1) Does modulation of potassium channels influence working memory performance in individuals with chronic cocaine use? and (2) How are potential effects related to behavioral responses observed during the experimental sessions?
To address these questions, a randomized, controlled, cross-over study will be conducted in participants with a history of chronic cocaine use. Participants will complete a series of neurocognitive tasks assessing working memory and related cognitive domains under controlled experimental conditions. Blood samples will be collected at multiple time points to quantify substance levels and to support the interpretation of behavioral findings. The results of this study may contribute to a better understanding of the neurobiological mechanisms underlying cognitive impairments in cocaine use and inform future research on cognitive dysfunction in substance use disorders.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 20 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Current diagnosis of mild, moderate, or severe CoUD according to DSM-5
- •Minimum cocaine use of 1g/month in the last three months
- •Cocaine as the primary drug of consumption
- •Willingness to abstain from cocaine use at least 72 hours before prior to each study visit
- •Ability to read, understand and provide written informed consent
- •To be sufficiently fluent in German
- •Age between 20 and 50 years
- •Body mass index (BMI) between 19 and 30 kg/m2
- •If applicable: luteal phase of the menstrual cycle
- •For individuals with childbearing potential: use of contraceptive measures
排除标准
- •Presence or history of severe neurological disorders or head injuries
- •Current diagnosis of an acute or chronic infectious disease
- •If applicable: pregnancy and breastfeeding
- •Lifetime history of any epileptic seizures
- •Lifetime diagnosis of a cardiovascular disease, specifically arrhythmia and long QT syndrome
- •Clinically significant laboratory or ECG abnormality that could be a safety issue in the study
- •Lifetime diagnosis of liver or kidney disease including moderate or severe renal impairment (creatinine clearance < 50 ml/min)
- •Known hypersensitivity or allergy to 4-aminopyridine
- •Use of potassium channel blockers within the last 3 months
- •Use of psychotropic medication within the last 7 days
- •Use of inhibitors of the organic cation transporter 2 (OCT2), such as cimetidine
- •Lifetime diagnosis of schizophrenia, bipolar disorder, obsessive-compulsive disorder, or autism spectrum disorder according to DSM-5
- •Diagnosis of a current episode of depression
- •Current diagnosis of a moderate or severe substance use disorder other than CoUD according than DSM-5
- •Daily cannabis consumption in the past three months
- •(E-Cigarette) Fagerström Test of Nicotine Dependence Score > 5 (strong nicotine dependence)
- •Inability to follow the procedures of the study, e.g., due to language problems
- •Being related to or in any form dependent on the investigator
- •Prior participation (less than two years ago) in a study investigating working memory using the n-back task, the SWM, PAL, RVP, or LNST
- •Participation in another study with investigational drugs within the 30 days preceding and during the present study
研究组 & 干预措施
Sequence AB
Participants receive fampridine (A) in one experimental session and placebo (B) in the other, in the order A then B.
干预措施: Placebo (Drug)
Sequence BA
Participants receive placebo (B) in one experimental session and fampridine (A) in the other, in the order B then A.
干预措施: Placebo (Drug)
Sequence AB
Participants receive fampridine (A) in one experimental session and placebo (B) in the other, in the order A then B.
干预措施: 4-aminopyridine (4-AP) (Drug)
Sequence BA
Participants receive placebo (B) in one experimental session and fampridine (A) in the other, in the order B then A.
干预措施: 4-aminopyridine (4-AP) (Drug)
结局指标
主要结局
Global Working Memory Performance
时间窗: Baseline and during both experimental sessions
Working memory performance will be assessed using a cognitive test battery covering different domains of working memory, including visuo-spatial (Spatial Working Memory \[SWM\], total errors; Paired Associates Learning \[PAL\], first trial memory score) and verbal-numeric components (Letter Number Sequencing Task \[LNST\], total score; Letter N-Back Task, discrimination index d'). Individual test scores will be standardized (z-transformation) and combined into a global working memory score according to Vonmoos et al (2013).
次要结局
- Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP)(Baseline and during both experimental sessions)
- Impulsivity(Baseline)
- Adverse effects(During both experimental sessions)
- Plasma concentration(During both experimental sessions)
- Heart rate variability(During both experimental sessions)
- Subjective ratings of current mood and craving(Baseline and during both experimental sessions)
- Adverse effects of the study drug(During both experimental sessions)
研究者
Boris Quednow
Full Professor for Experimental Pharmacopsychology and Psychological Addiction Research
Psychiatric University Hospital, Zurich