Multiple SclerosisPhase 2FAMPKINNCT01576354
Characterization of the Effects of Prolonged-release Fampridine on Ambulatory Function in Patients With Multiple Sclerosis
A Phase 2 study testing Prolonged-release Fampridine in people with Multiple Sclerosis, run by University of Zurich at 1 site in Switzerland.
Trial summary
The objective of the present investigator-initiated mono-center trial to be performed at the Department of Neurology of the University Hospital Zurich is a detailed characterization of the effects of prolonged-release fampridine on walking function of 50-70 patients with MS. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Prolonged-release Fampridine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 70 participants
- Where
- 1 siteSwitzerland
- Study dates
- Mar 2012to Apr 2017
- Phase
- Phase 2
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations.
- Male or female subjects must be 18 to 65 years old, inclusive, at the time of informed consent.
- Must have a diagnosis of either primary progressive, secondary progressive, progressive remitting, or relapsing remitting MS as defined by the revised McDonald Committee criteria [Lublin et al. 1996; McDonald et al. 2001; Polman et al. 2005; Section 22.4, Appendix L] of at least 3 months duration.
- Must be able to walk at least 50 meters (with or without a walking aid) at each individual 6minWT conducted pre-randomization.
- Must have an impaired walking function demonstrated by a mild gait ataxia (Functional System (FS) score = 2 in the cerebellar system component of the EDSS) or a FS score of > 2 in the pyramidal system component of the EDSS based only on evaluation of the lower limbs (hip flexors, knee flexors, knee extensors, and ankle dorsiflexors)or a restricted ambulation (< 1h walking duration) at the Screening Visit.
- Female subjects of childbearing potential must practice effective contraception during the study and be willing and able to continue contraception for 30 days after their last dose of study treatment.
Show all 19Show fewer
- Subjects must be able to understand the patient information sheet and comply with the requirements of the protocol.
- Main Exclusion Criteria:
- Any history of seizure, epilepsy, or other convulsive disorder, with the exception of febrile seizures in childhood.
- Any prior treatment with anti-epileptic medications specifically prescribed for the treatment of epilepsy.
- Onset of MS exacerbation within the 60 days prior to the Screening Visit.
- Use of mitoxantrone, cyclophosphamide, rituximab, alemtuzumab, daclizumab, cladribine or any other immune suppressant (except FTY720) or antibody (except natalizumab) within 3 months prior to the Screening Visit, or scheduled use during study participation.
- Pulsed steroid treatment within the 60 days prior to the Screening Visit, or at any time during the screening period.
- Women who are pregnant or breast feeding,
- Clinically significant concomitant disease states such as renal failure, (e.g., moderate or severe renal impairment), hepatic dysfunction (e.g., acute or chronic hepatitis), cardiovascular or pulmonary disease, malignant disease (tumor, neoplasia) etc.
- Participation in another study with investigational drug within the 30 days preceding and during the present study.
- Contraindications to the class of drugs under study, e.g. known allergy to pyridine-containing substances.
- Any prior treatment with fampridine (4-aminopyridine; 4 AP) or 3,4-diaminopyridine in any formulation.
- Patients with an acute urinary tract infection at the Screening Visit as indicated by symptoms like painful urination/dysuria, urinary frequency, urinary urgency, pollakiuria, suprapubic pain, flank pain, costovertebral angle tenderness or fever >38°C in combination with a clinically significant pathological finding in the urine analysis (e.g., positive for leukocytes) at the Screening.
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
University Hospital Zurich, Division of Neurology
Zurich, Canton of Zurich, 8091
About this study
Official title: A Phase IIb, Double-blind, Randomized, Mono-center, Placebo-controlled Study With Crossover Design Characterizing the Effects of Prolonged-release Fampridine Treatment on Ambulatory Function in Patients With Multiple Sclerosis Using Detailed Gait Analysis Based on Kinematic and Kinetic Parameters
The objective of the present investigator-initiated mono-center trial to be performed at the Department of Neurology of the University Hospital Zurich is a detailed characterization of the effects of prolonged-release fampridine on walking function of 50-70 patients with MS. In a randomized, double-blind, placebo-controlled study with cross-over design, changes of essential gait elements such as stability, coordination, correct loading, posture or endurance in addition to walking speed after treatment with prolonged-release fampridine will be investigated using a comprehensive kinematic gait analysis protocol. This protocol comprises outcome parameters ranging from very specific and sensitive biomechanical measures to clinically meaningful indicators of improved ambulatory function. Kinematic, kinetic and electromyographic gait parameters will be assessed during treadmill walking (primary outcome parameters). Changes in overground walking capacity will be investigated by means of different functional walking tests (e.g. six minute walk test). Furthermore, the patient's perception of the effects of the treatment on walking function will be evaluated by a standardized questionnaire. Changes of global ambulatory activity will be assessed (Actimeter) indicating a successful translation of improved gait (sub-)functions due to prolonged-release fampridine treatment into everyday life. The study will last for a period of 18 weeks, excluding the screening period. Based on the mechanism of action, the investigators hypothesize that treatment with prolonged-release fampridine will not only improve walking speed, but also clinically more meaningful features of walking function in patients with MS.
- Trial with medicinal product
- Conditions
- Multiple Sclerosis
- Being tested
- Prolonged-release Fampridine, Placebo
- Keywords
- Multiple Sclerosis, walking function, fampridine
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Prolonged-release FampridineDrug
Also called 4-aminopyridine, dalfampridine, ampyra, fampyra
10mg tablet twice a day (every 12 hours), orally
PlaceboDrug
tablet twice a day (every 12 hours), orally (matched placebo is provided as oval-shaped, white to off-white, matrix tablets. Each tablet contains the following inactive ingredients: colloidal silicon dioxide, hydroxypropyl methylcellulose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, and titanium dioxide)
| Study group | Role | What they receive |
|---|---|---|
| Prolonged-release Fampridine | Active comparator | Not described Receives: Drug: Prolonged-release Fampridine |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changed walking pattern on treadmill under fampridine treatment.
Electromyographic, kinematic and kinetic gait parameters describing stability, balance, posture, foot placement, loading, intra- and interlimb coordination and general dynamics of lower extremities will be recorded during treadmill walking.
Measured: Assessment during double-blind fampridine and double-blind placebo treatment (each for 6 weeks, assessments in week 4 and 6). Averaged values from the 2 different testing sessions per treatment period will be compared.
Secondary outcomes (9)
6 minute Walking Test
Measured: The test will be performed at all Visits (14) over a period of 18 weeks. Subjects will complete the task once per testing session/visit.
Timed 25-foot Walk test
Measured: The test will be performed 13 times over a period of 18 weeks. Subjects will complete the task four times per testing session/visit, two times with and two times without walking aids (in case walking aids are required).
Timed-Up-and-Go test
Measured: Subjects will complete the task two times per testing session/visit, once with and once without walking aids (in case walking aids are required). The task will be performed 4 times over a period of 18 weeks.
Berg Balance Scale
Measured: The subjects' performances are rated 4 times over a period of 18 weeks.
Dynamic Gait Index
Measured: The performance is rated 4 times over a period of 18 weeks.
LEMMT
modified British Medical Research Council (BMRC) manual muscle test: hip flexors, knee flexors, knee extensors, and ankle dorsiflexors
Measured: Lower Extremity Manual Muscle Test will be performed 4 times over a period of 18 weeks.
Actimeter
Measured: The device will be worn for 14 days during each double-blind treatment periods (two 6-weeks-periods).
12-item MS Walking Scale
Measured: Subjects are asked to complete the standardized questionnaire 4 times over a period of 18 weeks.
Fatigue Questionnaire (WEIMuS)
Measured: Subjects are asked to complete the standardized questionnaire at each visit except the Screening Visit (i.e., 13 times) over a period of 18 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2012 (estimated)
- Study startMar 2012
- Primary completionApr 2017 (estimated)
- Study completionApr 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by University of ZurichThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Zurich
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Michael Linnebank, MD, Principal investigator, University Hospital Zurich, Division of Neurology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01576354
- Sponsor's protocol ID
- FAMPKIN
- Acronym
- FAMPKIN
- Status last verified
- Dec 2015
- First submitted
- 22 Mar 2012
- Last updated
- 4 Dec 2015
- Results posted
- No
Publications
Zorner B, Hostettler P, Meyer C, Killeen T, Gut P, Linnebank M, Weller M, Straumann D, Filli L. Prognosis of walking function in multiple sclerosis supported by gait pattern analysis. Mult Scler Relat Disord. 2022 Jul;63:103802. doi: 10.1016/j.msard.2022.103802. Epub 2022 Apr 10.
PubMed 35487034Weller D, Filli L, Meyer C, Lorincz L, Linnebank M, Weller M, Curt A, Zorner B. Impaired speed-dependent modulation of the gait pattern in multiple sclerosis. J Neurol. 2020 Oct;267(10):2998-3007. doi: 10.1007/s00415-020-09965-3. Epub 2020 Jun 4.
PubMed 32500374Filli L, Werner J, Beyer G, Reuter K, Petersen JA, Weller M, Zorner B, Linnebank M. Predicting responsiveness to fampridine in gait-impaired patients with multiple sclerosis. Eur J Neurol. 2019 Feb;26(2):281-289. doi: 10.1111/ene.13805. Epub 2018 Oct 7.
PubMed 30171655Filli L, Zorner B, Kapitza S, Reuter K, Lorincz L, Weller D, Sutter T, Killeen T, Gruber P, Petersen JA, Weller M, Linnebank M. Monitoring long-term efficacy of fampridine in gait-impaired patients with multiple sclerosis. Neurology. 2017 Feb 28;88(9):832-841. doi: 10.1212/WNL.0000000000003656. Epub 2017 Feb 1.
PubMed 28148629Zorner B, Filli L, Reuter K, Kapitza S, Lorincz L, Sutter T, Weller D, Farkas M, Easthope CS, Czaplinski A, Weller M, Linnebank M. Prolonged-release fampridine in multiple sclerosis: Improved ambulation effected by changes in walking pattern. Mult Scler. 2016 Oct;22(11):1463-1475. doi: 10.1177/1352458515622695. Epub 2016 Jan 13.
PubMed 26762672
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IIb, Double-blind, Randomized, Mono-center, Placebo-controlled Study With Crossover Design Characterizing the Effects of Prolonged-release Fampridine Treatment on Ambulatory Function in Patients With Multiple Sclerosis Using Detailed Gait Analysis Based on Kinematic and Kinetic Parameters
- ClinicalTrials.gov ID
- NCT01576354
- Acronym / sponsor ID
- FAMPKIN / FAMPKIN
- Conditions
- Multiple Sclerosis
- Keywords
- Multiple Sclerosis, walking function, fampridine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- University of ZurichUniversity, hospital or other
- Study start
- Mar 2012
- Primary completion
- Apr 2017 (estimated)
- Study completion
- Apr 2017 (estimated)
- First posted
- 12 Apr 2012 (estimated)
- 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.
The objective of the present investigator-initiated mono-center trial to be performed at the Department of Neurology of the University Hospital Zurich is a detailed characterization of the effects of prolonged-release fampridine on walking function of 50-70 patients with MS. In a randomized, double-blind, placebo-controlled study with cross-over design, changes of essential gait elements such as stability, coordination, correct loading, posture or endurance in addition to walking speed after treatment with prolonged-release fampridine will be investigated using a comprehensive kinematic gait analysis protocol. This protocol comprises outcome parameters ranging from very specific and sensitive biomechanical measures to clinically meaningful indicators of improved ambulatory function. Kinematic, kinetic and electromyographic gait parameters will be assessed during treadmill walking (primary outcome parameters). Changes in overground walking capacity will be investigated by means of different functional walking tests (e.g. six minute walk test). Furthermore, the patient's perception of the effects of the treatment on walking function will be evaluated by a standardized questionnaire. Changes of global ambulatory activity will be assessed (Actimeter) indicating a successful translation of improved gait (sub-)functions due to prolonged-release fampridine treatment into everyday life. The study will last for a period of 18 weeks, excluding the screening period. Based on the mechanism of action, the investigators hypothesize that treatment with prolonged-release fampridine will not only improve walking speed, but also clinically more meaningful features of walking function in patients with MS.
- Trial with medicinal product
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 |
|---|---|---|
| Prolonged-release Fampridine | Active comparator | Drug: Prolonged-release Fampridine |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations.
- Male or female subjects must be 18 to 65 years old, inclusive, at the time of informed consent.
- Must have a diagnosis of either primary progressive, secondary progressive, progressive remitting, or relapsing remitting MS as defined by the revised McDonald Committee criteria [Lublin et al. 1996; McDonald et al. 2001; Polman et al. 2005; Section 22.4, Appendix L] of at least 3 months duration.
- Must be able to walk at least 50 meters (with or without a walking aid) at each individual 6minWT conducted pre-randomization.
- Must have an impaired walking function demonstrated by a mild gait ataxia (Functional System (FS) score = 2 in the cerebellar system component of the EDSS) or a FS score of > 2 in the pyramidal system component of the EDSS based only on evaluation of the lower limbs (hip flexors, knee flexors, knee extensors, and ankle dorsiflexors)or a restricted ambulation (< 1h walking duration) at the Screening Visit.
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| Prolonged-release FampridineAlso: 4-aminopyridine, dalfampridine, ampyra, fampyra10mg tablet twice a day (every 12 hours), orally | Drug | Prolonged-release Fampridine |
| Placebotablet twice a day (every 12 hours), orally (matched placebo is provided as oval-shaped, white to off-white, matrix tablets. Each tablet contains the following inactive ingredients: colloidal silicon dioxide, hydroxypropyl methylcellulose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, and titanium dioxide) | Drug | Placebo |
Primary outcome
Changed walking pattern on treadmill under fampridine treatment.
Time frame: Assessment during double-blind fampridine and double-blind placebo treatment (each for 6 weeks, assessments in week 4 and 6). Averaged values from the 2 different testing sessions per treatment period will be compared.
Electromyographic, kinematic and kinetic gait parameters describing stability, balance, posture, foot placement, loading, intra- and interlimb coordination and general dynamics of lower extremities will be recorded during treadmill walking.
9 secondary outcomes
6 minute Walking Test
Time frame: The test will be performed at all Visits (14) over a period of 18 weeks. Subjects will complete the task once per testing session/visit.
Timed 25-foot Walk test
Time frame: The test will be performed 13 times over a period of 18 weeks. Subjects will complete the task four times per testing session/visit, two times with and two times without walking aids (in case walking aids are required).
Timed-Up-and-Go test
Time frame: Subjects will complete the task two times per testing session/visit, once with and once without walking aids (in case walking aids are required). The task will be performed 4 times over a period of 18 weeks.
Berg Balance Scale
Time frame: The subjects' performances are rated 4 times over a period of 18 weeks.
Dynamic Gait Index
Time frame: The performance is rated 4 times over a period of 18 weeks.
LEMMT
Time frame: Lower Extremity Manual Muscle Test will be performed 4 times over a period of 18 weeks.
Actimeter
Time frame: The device will be worn for 14 days during each double-blind treatment periods (two 6-weeks-periods).
12-item MS Walking Scale
Time frame: Subjects are asked to complete the standardized questionnaire 4 times over a period of 18 weeks.
Fatigue Questionnaire (WEIMuS)
Time frame: Subjects are asked to complete the standardized questionnaire at each visit except the Screening Visit (i.e., 13 times) over a period of 18 weeks.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2015.
- Derived from this study: PubMed 35487034Zorner B, Hostettler P, Meyer C, Killeen T, Gut P, Linnebank M, Weller M, Straumann D, Filli L. Prognosis of walking function in multiple sclerosis supported by gait pattern analysis. Mult Scler Relat Disord. 2022 Jul;63:103802. doi: 10.1016/j.msard.2022.103802. Epub 2022 Apr 10.
- Derived from this study: PubMed 32500374Weller D, Filli L, Meyer C, Lorincz L, Linnebank M, Weller M, Curt A, Zorner B. Impaired speed-dependent modulation of the gait pattern in multiple sclerosis. J Neurol. 2020 Oct;267(10):2998-3007. doi: 10.1007/s00415-020-09965-3. Epub 2020 Jun 4.
- Derived from this study: PubMed 30171655Filli L, Werner J, Beyer G, Reuter K, Petersen JA, Weller M, Zorner B, Linnebank M. Predicting responsiveness to fampridine in gait-impaired patients with multiple sclerosis. Eur J Neurol. 2019 Feb;26(2):281-289. doi: 10.1111/ene.13805. Epub 2018 Oct 7.
- Derived from this study: PubMed 28148629Filli L, Zorner B, Kapitza S, Reuter K, Lorincz L, Weller D, Sutter T, Killeen T, Gruber P, Petersen JA, Weller M, Linnebank M. Monitoring long-term efficacy of fampridine in gait-impaired patients with multiple sclerosis. Neurology. 2017 Feb 28;88(9):832-841. doi: 10.1212/WNL.0000000000003656. Epub 2017 Feb 1.
- Derived from this study: PubMed 26762672Zorner B, Filli L, Reuter K, Kapitza S, Lorincz L, Sutter T, Weller D, Farkas M, Easthope CS, Czaplinski A, Weller M, Linnebank M. Prolonged-release fampridine in multiple sclerosis: Improved ambulation effected by changes in walking pattern. Mult Scler. 2016 Oct;22(11):1463-1475. doi: 10.1177/1352458515622695. Epub 2016 Jan 13.
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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.
Michael Linnebank, MD principal investigator
University Hospital Zurich, Division of Neurology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Prolonged-release Fampridine in people with Multiple Sclerosis, run by University of Zurich 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 19 inclusion and 0 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: status not confirmed, as of the sponsor's last update on 4 Dec 2015. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
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?
Changed walking pattern on treadmill under fampridine treatment. (time frame: Assessment during double-blind fampridine and double-blind placebo treatment (each for 6 weeks, assessments in week 4 and 6). Averaged values from the 2 different testing sessions per treatment period will be compared.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01576354, which also lists 5 linked publications.
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 4 Dec 2015.