Randomized Placebo-controlled Phase II Cross-over Study on the Influence of Fampridine on Working Memory in Individuals With Post COVID-19 Condition With Subjective Cognitive Impairment
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 发起方
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Digits Span backward performance
研究概览
简要总结
In genome-wide association studies we identified potassium channels to be genetically linked to performance and neural activity of working memory in healthy humans. Furthermore, there is evidence in rodents and non-human primates that pharmacological blockade of potassium channels can improve working memory.
In the present study, we aim at investigating the effects of 10 mg fampridine (4-Aminopyridine), a potassium channel-blocking agent, on working memory performance in individuals with Post-COVID-19-Condition with subjective cognitive impairment. The hypothesis is that fampridine improves working memory performance.
Fampridine, especially its slow-release formulation (Fampyra®) is generally a safe drug with well-studied pharmacokinetic properties. It crosses the blood-brain barrier and reaches maximum concentration in the brain approximately 3.5h after single-dose administration. Evidence suggests that fampridine improves walking speed in patients with multiple sclerosis (MS), which led to FDA and EMA approval for this indication. The mode of action by which fampridine improves walking speed is probably its blockade of a spectrum of potassium channels that are exposed in demyelinated axons, leading to mitigation of potassium leakage and normalization of nerve conduction. Additionally, an action of fampridine at central synapses and increase of neurotransmitter release has been discussed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 69 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •male or female;
- •a valid positive PCR test or a documented certified rapid antigen test or a virus-specific antibody (nucleocapsid) test for COVID-19 issued at least 3 months prior to study;
- •Above medium subjective working memory impairment (at least "much worse" in item 1a part 2 (cognitive abilities) of the Covid-Q screening questionnaire;
- •present at least 3 months after COVID-19 infection and lasting for at least 2 months. (The impairment must have emerged after COVID-19 infection and cannot be explained by an alternative diagnosis);
- •normotensive (BP: 90/60mmHg - 140/90mmHg);
- •BMI: 19.0 - 40.0 kg/m2;
- •Age: 18 - 69 years;
- •fluent German-speaking;
- •IC as documented by signature.
排除标准
- •initiation of pharmacological treatment or change of dose within the 30 days preceding the present study
- •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
- •concomitant treatment with OCT 2 inhibitors and -substrates (e.g. cimetidine, propranolol)
- •acute or chronic psychiatric disorder (e.g. major depression, psychosis, somatoform disorder, suicidal tendency)
- •acute cerebrovascular condition
- •history of seizures
- •risk of lowered seizure threshold (due to e.g. sleep deprivation, withdrawal of alcohol after alcohol abuse)
- •renal impairment
- •history of malignant cancers
- •walking problems (e.g. due to dizziness)
- •other clinically significant concomitant disease states that could pose a safety risk (e.g. hepatic dysfunction, cardiovascular disease, urinary tract infection)
- •bradycardia < 50/min during clinical examination
- •clinically significant laboratory or ECG abnormality that could be a safety issue in the study
- •known or suspected non-compliance (e.g. missing more than one dose of study medication per intervention phase)
- •drug or alcohol abuse
- •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
- •pregnancy or breast feeding
- •Intensive care treatment due to COVID-19 infection.
- •Exclusion Criteria concerning TMS measurement
- •metal in the brain, skull or elsewhere in the body (e.g., splinters, fragments, clips, etc.)
- •implanted neurostimulator (e.g., DBS, epidural/subdural, VNS)
- •cardiac pacemaker or intracardiac lines
- •medication infusion device
- •piercings in the head area, pivot teeth (retainers are no exclusion criterion)
- •tattoos (in the head area) with metallic inks or newly stung tattoos (< 3 months), as newly stung tattoos can be damaged by a magnetic field;
- •condition after neurosurgery
- •hearing problems or tinnitus
- •not able to sit still due to tremor, tics, itching
- •History of repeated syncope
- •head trauma diagnosed as concussion or associated with loss of consciousness
- •diagnosis of epilepsy, or a convulsion or a seizure in the past of the participant or his family
- •TMS in the past showing problems
- •MRI in the past showing problems
- •surgical procedures to spinal cord
- •spinal or ventricular derivations TMS measurement is optional. If a participant is eligible for the study, but prefers not to undergo TMS measurement or meets one or more exclusion criteria for TMS measurement, the participant can nevertheless be included in the study without rMT measurement using TMS.
研究组 & 干预措施
Fampridin SR
Active study medication consists of 7 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 8 days equaling over 30 half-lives of the active substance fampridine (t½ = 6 h) between experimental and control intervention and up to 26 days depending on the individual scheduling of each subject.
干预措施: Fampridine SR (Drug)
Placebo
Identically looking placebo tablets consisting of widely identical additives formulated for oral administration.
干预措施: Placebo (Drug)
结局指标
主要结局
Digits Span backward performance
时间窗: first and last day of 3.5-days-treatment periods (each 4 hours after intake in the morning); to assess changes between the verum and placebo condition
The Digit Span task is a subtest of an intelligence test for adults ("Wechsler Intelligenztest für Erwachsene" (WIE; (von Aster 2006)). Total scores for digit span backward will be calculated as described in the manual of the WIE. Minimum 0 points and maximum 12 points. Parallel version will be used for the altogether four assessments at the beginning (visits 2 and 4) and at the end (visits 3 and 5) of both treatment phases.
次要结局
- Digits Span forward performance(first and last day of 3.5-days-treatment periods (each 4 hours after intake in the morning); to assess changes between the verum and placebo condition)
- Lexical ability(first and last day of 3.5-days-treatment periods (each 4 hours after intake in the morning); to assess changes between the verum and placebo condition)
- Red Button Task(first and last day of 3.5-days-treatment periods (each 4 hours after intake in the morning); to assess changes between the verum and placebo condition)
- Symbol Digit Modalities Test, SDMT(first and last day of 3.5-days-treatment periods (each 4 hours after intake in the morning); to assess changes between the verum and placebo condition)
- Verbal episodic memory performance (word list)(first and last day of 3.5-days-treatment periods (each 4 hours after intake in the morning); to assess changes between the verum and placebo condition)
- Bochumer Matrizentest (BOMAT - standard)(first and last day of 3.5-days-treatment periods (each 4 hours after intake in the morning); to assess changes between the verum and placebo condition)
- Resting motor threshold (rMT)(test days 2 and 4 (last day of treatment periods; approx. 5 hours after last intake of fampridine SR) to assess differences between the verum and placebo condition)
- Subjective cognitive impairment(during the three 3 days of the treatment phase as compared to the 3 days before treatment; to assess changes between the verum and placebo condition)
研究者
Prof. Dominique de Quervain, MD
Director Division of Cognitive Neuroscience,
University of Basel