Working MemoryFamCNCT05274477
Influence of Fampridine on Working Memory in Individuals With Post COVID-19 Condition With Subjective Cognitive Impairment
A study testing Fampridine SR in people with Working Memory and Post-covid-19, run by Prof. Dominique de Quervain, MD at 1 site in Switzerland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 69 years
- Conditions the study is for
- Working Memory, Post-covid-19
- What is being tested?
- Fampridine SR
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 8 participants
- Where
- 1 siteSwitzerland
- Study dates
- 28 Jun 2022to 30 Jun 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 69 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
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- Age: 18 - 69 years;
- fluent German-speaking;
- IC as documented by signature.
Who cannot join
- 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
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- 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
- 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.
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
University of Basel, Transfaculty Research Platform
Basel, Canton of Basel-City, 4055
About this study
Official title: 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
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
- Being tested
- Fampridine SR, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fampridine SRDrug
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).
PlaceboDrug
no active component
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Fampridine SR |
| Placebo | Placebo comparator | Identically looking placebo tablets consisting of widely identical additives formulated for oral administration. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: 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
Reaction time test (Red Button Task), adapted from (Dinges and Powell, 1985): participant sits in front of a screen showing a gray circle in the middle of the screen. The circle's color turn into red and participant will be instructed to push a button as soon as the color changes. The period between the time of color change and button push is measured in miliseconds and will be considered as reaction time.
Measured: 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
Symbol Digit Modalities Test, SDMT (Smith 2013, 13th edition), a processing speed test. The test consists of the presentation of a series of 9 symbols, each of them is paired with a single digit, labelled 1-9, in a key at the top of a sheet. The remainder of the page has a pseudorandomized sequence of the symbols and the participant must respond with the digit associated with each of these as quickly as possible. The score is the number of correct answers in 90 seconds. The administration of SDMT will be preceded by a learning sequence at both timepoints. It will be used parallel versions for all test days.
Measured: 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)
Verbal episodic memory performance (15 words) measured by immediate and delayed word-list recall. Adapted from a subtest of the German test called "Verbaler Lern- und Merkfähigkeits-Test" (VLMT; Helmstaedter/Lendt/Lux, 2001).
Measured: 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
Lexical ability measured by phonemic fluency test after acute and repeated intake of study medication (S-words); adapted from a subtest of the German test called "Regensburger Wortflüssigkeits-Test" (RWT; Aschenbrenner/Tucha/Lange, 2001). In this task participants should name orally as many words as possible initiating with a special letter in one minute (e.g. Mary, Milk, Mouse, etc. for the letter M) the number of unique meaningful words will be considered as the participant's score.
Measured: 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)
Fluid intelligence (Gf) will be measured with the Bochumer Matrizentest (BOMAT - standard; Hossiep/Hasella, 2010, 1st edition), matrix reasoning. BOMAT - standard consisting of 30 items will be administered. 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. To create four versions, the original BOMAT versions A and B have been divided each into two versions (every second item) with 15 items each. A time-limited version (10 minutes) will be used to avoid a ceiling effect. The total score is calculated by summing the correct solutions, ranging between 0 to 15.
Measured: 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
Subjective cognitive impairment
Subjective cognitive symptoms are assessed with a self-administered questionnaire at the end of both treatment phases (visits 3 and 5). The participants are asked to rate the changes of cognitive abilities during the three 3 days of the treatment phase as compared to the 3 days before treatment on a 7 point likert scale (much worse - (…) - unchanged - (…) much better).This questionnaire contains questions about several domains of cognitive function (working memory, episodic memory, attention and concentration, executive function, lexical ability).
Measured: 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
Resting motor threshold (rMT)
The resting motor threshold (rMT) will be measured by transcranial magnetic stimulation (TMS). rMT will be determined by measuring the motor evoked potential (MEP) in the abductor digiti
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2022
- Study start28 Jun 2022
- Primary completion30 Jun 2024
- Study completion30 Jun 2024
Why it stopped: Recruitment difficulties
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Working MemoryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Prof. Dominique de Quervain, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Clinical Trial Unit, University Hospital Basel, Switzerland, University Hospital, Basel, Switzerland
- Responsible party
- Sponsor-investigator, Prof. Dominique de Quervain, MD, University of Basel
- Investigators
- Dominique de Quervain, Prof. MD, Study chair, University of Basel, Transfaculty Research PlatformAndreas Papassotiropoulos, Prof. MD, Study chair, University of Basel, Transfaculty Research Platform
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05274477
- Sponsor's protocol ID
- 2022-00452
- Acronym
- FamC
- Status last verified
- Jul 2024
- First submitted
- 3 Mar 2022
- Last updated
- 18 Jul 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All IPD (de-identified) that underline results in a publication will be shared upon reasonable request.
Study at a glance
From the registry record, last updated by the sponsor on 18 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05274477
- Acronym / sponsor ID
- FamC / 2022-00452
- Conditions
- Working Memory, Post-covid-19
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Recruitment difficulties
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Prof. Dominique de Quervain, MDUniversity, hospital or other
- Collaborators
- Clinical Trial Unit, University Hospital Basel, Switzerland, University Hospital, Basel, Switzerland
- Study start
- 28 Jun 2022 (actual)
- Primary completion
- 30 Jun 2024 (actual)
- Study completion
- 30 Jun 2024 (actual)
- First posted
- 10 Mar 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fampridin SR | Experimental | Drug: Fampridine SRActive 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. |
| Placebo | Placebo comparator | Drug: PlaceboIdentically looking placebo tablets consisting of widely identical additives formulated for oral administration. |
Who may qualify
- Ages
- 18 to 69 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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);
Key exclusion criteria (37 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fampridine SRFampridine 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). | Drug | Fampridin SR |
| Placebono active component | Drug | Placebo |
Primary outcome
Digits Span backward performance
Time frame: 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.
8 secondary outcomes
Digits Span forward performance
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: 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
Time frame: 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)
Time frame: 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
Subjective cognitive impairment
Time frame: 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
Resting motor threshold (rMT)
Time frame: 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
Results and safety
The study was stopped early (reason given: Recruitment difficulties). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2024.
- Individual participant dataSharing planned: Yes. All IPD (de-identified) that underline results in a publication will be shared upon reasonable request.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dominique de Quervain, Prof. MD study chair
University of Basel, Transfaculty Research Platform
Andreas Papassotiropoulos, Prof. MD study chair
University of Basel, Transfaculty Research Platform
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Fampridine SR in people with Working Memory and Post-covid-19, run by Prof. Dominique de Quervain, MD at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 18 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Recruitment difficulties). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Digits Span backward performance (time frame: 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jul 2024.