Primary objective: - to evaluate the effects of fampridine on eye movements in MS patients with a unilateral or bilateral INO. Secondary objectives:- to determine whether there is an association between MRI signal of the medial longitudinal…
ID
Source
Brief title
Condition
- Demyelinating disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Eye movements at each day and time point. Variables will include (but not limit
to):
- eye position and velocity at the abducting/adducting eye
-Versional disconjugacy index: the inter-ocular ratio of the peak velocity and
peak acceleration of the abducting and adducting eye.
-first-pass amplitude: the ratio of the position of the abducting eye to the
adducting eye when both eyes reached their final position of ocular
displacement with respect to the target position.
- peak velocity ratio for each saccade
- saccade pulse in the 2 eyes
Secondary outcome
A MRI-scan brain:
- signal intensity MLF
- length of MLF
Nerve conduction speed as determined by lag time of the adducting eye divided
by the length of the MLF
Cognitive function test items from NeuroCart:
- Adaptive tracking (motor-coordination)
- Body sway (postural stability)
- Rapid visual information processing (RVIP)
- Simple reaction time task
- Symbol Digit Substitution Test (SDST, cognitive processing speed)
- Pharmaco-EEG
Pharmacokinetic endpoints: Tmax, Cmax, AUCinf, t1/2, Vd/f, CL/F
Safety endpoints: Pulse, diastolic blood pressure, systolic blood pressure.
Background summary
Fampridine is a potassium channel blocker which leads to inhibition of leakage
of potassium ions causing a prolongation of repolarisation and hence
improvement of formation of action potentials in demyelinated nerve fibres.
Fampridine has been shown to enhance neurological functioning in patients with
relapsing remitting MS (an improvement of approximately 25% was observed on
walking speed), but there is very limited evidence about fampridine use in MS
patients with internuclear ophtalmoplegia (INO).
Methods to quantify de- and remyelination and methods to quantify nerve
conduction of demyelinated nerves are needed to investigate pharmacological
effects of new compounds that are aimed at improving remyelination or improving
nerve function of demyelinated nerve fibres, which are currently being
developed for the treatment of MS.
This study will be performed in MS patients with slowing of eye adduction
consistent with subclinical or clinically overt unilateral or bilateral INO, to
determine whether a change of nerve conduction and function can be observed
after administration fampridine.
Study objective
Primary objective:
- to evaluate the effects of fampridine on eye movements in MS patients with a
unilateral or bilateral INO.
Secondary objectives:
- to determine whether there is an association between MRI signal of the medial
longitudinal fasciculus (MLF) and the nerve conduction velocity in MS patients
with INO.
-to evaluate the efficacy of fampridine on neurophysiology as measured using
NeuroCart test battery.
-to establish a pharmacokinetic-pharmacodynamic model for the effect of
fampridine on eye movement in MS patients with INO.
Study design
This will be a randomized, double-blind, placebo-controlled, cross-over study
with fampridine in patients with MS and a unilateral or bilateral INO.
Intervention
Fampridine 20 mg, once during the study.
Study burden and risks
There is no direct benefit for the subjects taking part in this study. The
results of the study may provide valuable information for future research.
Incidentally, subjects participating this study will get a headache. This can
be caused by not eating for a certain period of time or drinking no coffee.
Placement of a canula can cause a bruise.
In therapy with fampridine sometimes also adverse events can occur, such as:
urinary tract infections, anxiety, dizziness, headache, paresthesia, tremor,
laryngeal pain and gastrointestinal disorders such as nausea, vomiting and
dyspepsia.
Zernikedreef 8
Leiden 2333CL
NL
Zernikedreef 8
Leiden 2333CL
NL
Listed location countries
Age
Inclusion criteria
1. Male and female patients 18 years or more of age;
2. Diagnosis of multiple sclerosis according to the revised McDonald (2005) criteria;
3. A disease duration > 1 year as defined by a diagnosis of MS at least one year prior to inclusion in the study;
4. Clinically stable disease > 30 days;
5. Subject shows evidence of INO by quantitative neuro-ophthalmological criteria;
6. Subject is able to understand the demands of the protocol, has had any questions answered and has voluntarily signed the informed consent prior to any study procedures; and
7. Subject is otherwise in good health, based on complete medical history and physical examination, including blood pressure and pulse rate measurement, 12-lead ECG, and clinical laboratory tests.
Exclusion criteria
1. Subject is a pregnant female (as determined by a urine pregnancy test), a lactating female, or a female of child-bearing potential, not sterilized and not using one of the following methods of birth control: oral or injectable contraceptive agent, implantable contraceptive device, or barrier method;
2. The neuro-ophthalmological examination demonstrates significant impairment of eye-movements due to cerebellar or other pathology which may infer with reliable testing of an INO;
3. Inability of a subject to maintain good visual fixation;
4. Subject has a prior history or current presentation of seizure;
5. Subject has a creatinine clearance less than 80 mL/min, calculated by Cockroft-Gault equation;
6. Subject has known allergy to fampridine;
7. Subject has any contraindication of MRI;
8. The subject has any medical condition, including psychiatric disease that might interfere with the interpretation of the results or with the conduct of the study;
9. Subject has a history of drug or ethanol abuse within the past year;
10. A positive urine drug screen;
11. Subject has a history of ischemic heart disease;
12. Concomitant use of fampridine with medicinal products that are inhibitors or substrates of organic cation transporter 2 (OCT2) such as cimetidine, carvedilol, propanolol and metformin;
13. Treatment with another investigational drug within 3 months prior to screening or having participated in more than 4 investigational drug studies within 1 year prior to screening; and/or
14. The subject has abnormal clinical laboratory values or an abnormal ECG, without approval of the study investigator.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2015-000182-31-NL |
| CCMO | NL52195.056.15 |