Influence of Fampridine on Working Memory in Individuals With Post COVID-19 Condition With Subjective Cognitive Impairment

NCT ID: NCT05274477

Last Updated: 2024-07-18

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-28
• Study Completion Date: 2024-06-30

Brief Summary

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.

Conditions

Working Memory; Post-covid-19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Fampridine SR

Intervention Type: DRUG

Fampridine SR is an inhibitor of voltage gated potassium channels and is approved in Switzerland for treatment of gait problems in patients with Multiple Sclerosis (MS).

Placebo

Identically looking placebo tablets consisting of widely identical additives formulated for oral administration.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

no active component

Interventions

Fampridine SR

Fampridine SR is an inhibitor of voltage gated potassium channels and is approved in Switzerland for treatment of gait problems in patients with Multiple Sclerosis (MS).

Intervention Type: DRUG

Placebo

no active component

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 69 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Clinical Trial Unit, University Hospital Basel, Switzerland

OTHER

Sponsor Role: collaborator

University Hospital, Basel, Switzerland

OTHER

Sponsor Role: collaborator

Prof. Dominique de Quervain, MD

OTHER

Sponsor Role: lead

Responsible Party

Prof. Dominique de Quervain, MD

Director Division of Cognitive Neuroscience,

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Dominique de Quervain, Prof. MD

Role: STUDY_CHAIR

University of Basel, Transfaculty Research Platform

Andreas Papassotiropoulos, Prof. MD

Role: STUDY_CHAIR

University of Basel, Transfaculty Research Platform

Locations

University of Basel, Transfaculty Research Platform

Basel, Canton of Basel-City, Switzerland

Countries

Switzerland

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2022-00452

Identifier Type: -

Identifier Source: org_study_id