Autonomic Nervous System Dysfunction, Multiple Sclerosis
Conditions
Keywords
relapsing remitting, multiple sclerosis, fingolimod, Gilenya, autonomic nervous system
Brief summary
This study is designed to primarily evaluate the impact of Gilenya (Fingolimod) on the autonomic nervous system in patients being treated for the first time with Gilenya (Fingolimod). Effects on the cardiovascular system will be studied as well. The study is conducted to answer the question, if, and if yes, what impact the treatment with Gilenya (Fingolimod) has on the autonomic nervous system. To our knowledge little is known about the effects of Gilenya (Fingolimod) on the autonomic nervous system. We do know of rare, but potentially clinically and therapeutically relevant cardiovascular adverse events of Gilenya (Fingolimod). From a scientific point of view the mechanisms by which this is mediated are of interest. Maybe a better understanding of these mechanisms might even be of clinical relevance (e.g. risk stratification). The impact of Gilenya (Fingolimod) on the autonomic nervous system is quantitavely measured, using a state-of-the-art technique. Non-invasive blood pressure measurement is performed with the Finometer Pro (Finapres Medical Systems, NL) under different paradigms (breathing at rest, deep breath, valsalva maneuver, active standing). In addition the sympathetic skin reaction is performed. The non-invasive blood pressure measurements are done by continuous, plethysmographic blood pressure measurement at the index finger, while the patient is performing the tasks mentioned above. By interpreting the blood pressure curve, heart rate and blood pressure variability are calculated. The sympathetic skin reaction consists of measuring the change of electric conductibility of the skin (palms and soles) after an electric stimulus of a peripheral nerve. These parameters allow to assess the functionality of four important autonomic functional systems (orthostasis, sympathetic adrenergic, sympathetic cholinergic, parasympathetic cholinergic). Normative data has been acquired in our lab. Our hypothethis is, that there will be a change of heart rate variability at t4,5h compared to baseline (t0) for the parameter RMSSD under normal breathing.
Interventions
DRUGGilenya
Autonomic testing during first dose administration of Gilenya.
Sponsors
Jochen Vehoff
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* indication for treatment with Gilenya according label * treatment with Gilenya intended * no contraindications for the treatment with Gilanya * all safety-aspects have been fullfilled * age between 18 and 60 years * written consent is given
Exclusion criteria
* relapse during the last 30 days befor randomization * steroids within 30 days before randomization * heart rhythm disturbance * new or currently changed dose (last 4 weeks) of bata-blockers, calcium antagonists, antidepressants or antiarrhythmics * diabetes mellitus * polyneuropathy * missing consent * pregnancy * lactation period
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| RMSSD Normal Breathing | t-4,5 hours | Root Mean Square of the Successive Differences (RMSSD) is one of a few time-domain tools used to assess heart rate variability, the successive differences being neighboring RR or pulse intervals. It is calculated as the square root of the mean of the squares of the successive differences between adjacent RR intervals or pulse intervals. In this study pulse intervals were measured non-invasively during five minutes, while subjects were supine, breathing regularly. Measurements were done at two timepoints t=0 and t=4,5hours. RMSSD was compared between these two timepoints. |
Countries
Switzerland
Participant flow
Recruitment details
First patient in: 21.08.2013 Last patient out: 16.06.2015
Participants by arm
| Arm | Count |
|---|---|
| Gilenya Gilenya 0.5mg p.o. once daily | 33 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | Gilenya |
|---|---|
| Age, Continuous | 37.57 years STANDARD_DEVIATION 12.44 |
| Body temperature | 36.58 °C STANDARD_DEVIATION 0.45 |
| EDSS | 1.75 units on a scale STANDARD_DEVIATION 1.16 |
| Height | 168.72 cm STANDARD_DEVIATION 7.98 |
| Region of Enrollment Switzerland | 33 participants |
| Sex: Female, Male Female | 25 Participants |
| Sex: Female, Male Male | 8 Participants |
| Weight | 71.18 kg STANDARD_DEVIATION 13.18 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 1 / 33 |
| serious Total, serious adverse events | 2 / 33 |
Outcome results
Primary
RMSSD Normal Breathing
Root Mean Square of the Successive Differences (RMSSD) is one of a few time-domain tools used to assess heart rate variability, the successive differences being neighboring RR or pulse intervals. It is calculated as the square root of the mean of the squares of the successive differences between adjacent RR intervals or pulse intervals. In this study pulse intervals were measured non-invasively during five minutes, while subjects were supine, breathing regularly. Measurements were done at two timepoints t=0 and t=4,5hours. RMSSD was compared between these two timepoints.
Time frame: t-4,5 hours
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Gilenya | RMSSD Normal Breathing | 14.10 milliseconds |
p-value: 0.02t-test, 1 sided