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

NCT05274477 | Terminated DMC

• 1 other identifier: 2022-00452
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Digits Span backward performance

  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.

  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

Secondary Outcomes (8)

• 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

• 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

• 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

Study Arms (2)

Fampridin SR

EXPERIMENTAL

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.

Drug: Fampridine SR

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Fampridine SR 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).

Fampridin SR

Placebo DRUG

no active component

Placebo

Eligibility Criteria

• Age: 18 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Prof. Dominique de Quervain, MD: lead
• Clinical Trial Unit, University Hospital Basel, Switzerland: collaborator
• University Hospital, Basel, Switzerland: collaborator

Study Sites (1)

University of Basel, Transfaculty Research Platform

Basel, Canton of Basel-City, 4055, Switzerland

Location

MeSH Terms

Interventions

4-Aminopyridine

Intervention Hierarchy (Ancestors)

Aminopyridines; Amines; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Dominique de Quervain, Prof. MD

  University of Basel, Transfaculty Research Platform

  STUDY CHAIR

• Andreas Papassotiropoulos, Prof. MD

  University of Basel, Transfaculty Research Platform

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director Division of Cognitive Neuroscience,

Study Record Dates

• First Submitted: March 3, 2022
• First Posted: March 10, 2022
• Study Start: June 28, 2022
• Primary Completion: June 30, 2024
• Study Completion: June 30, 2024
• Last Updated: July 18, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: IPD will be available after publication, study protocol (including statistical analysis plan) will be made available before start of the study.
• Access Criteria: All IPD (de-identified) that underline results in a publication will be shared upon reasonable request for scientific purposes. A reasonable request consists of a short description of the scientific purpose. Request will be reviewed by the team of the principal investigator.

Locations

CH (1)