The key objectives of this study are:1. To determine by means of IENFD whether the PNS is involved in patients with autonomic complaints in MS. The obtained IENFD values will be compared with the age and gender matched healthy normative data,…
ID
Source
Brief title
Condition
- Demyelinating disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary analysis will consider the difference in IENFD between MS patients
with symptoms and without symptoms of ANS dysfunction, as well as compared to
healthy participants.
Secondary outcome
In secondary analysis the results of the IENFD will be related to the other
outcome measures and clinical data.
Background summary
Multiple sclerosis (MS) is a chronic inflammatory disseminated illness of the
central nervous system (CNS). White matter lesions are considered the hallmark
of MS. Autonomic nervous system (ANS) failure in MS may also occur and has been
reported in 10% to 90% of patients and may lead to various organ involvement,
as well as a decrease in quality of life expectations. It remains unclear
whether the expression of the peripheral autonomic involvement is present in
MS. Peripheral ANS dysfunction, as an expression of small fibre neuropathic
dysfunction (SFN) preferentially affects small-calibre myelinated (A*) and
unmyelinated (C) fibres, leaving the larger myelinated fibres relatively
unaffected. The diagnosis SFN is made on the basis of the clinical features,
normal nerve conduction studies, and abnormal specialized tests of small nerve
fibres. No gold standard test exists for assessing ANS dysfunction in MS. It is
also not known whether ANS dysfunction in MS is related to PNS involvement. A
clearly defined standardization is necessary to describe the prevalence of the
various aspects of autonomic dysfunction in patients with MS, including the
challenges within the various forms and stages of the disease, e.g., at onset,
according to different courses, or accompanying relapses.
Study objective
The key objectives of this study are:
1. To determine by means of IENFD whether the PNS is involved in patients with
autonomic complaints in MS.
The obtained IENFD values will be compared with the age and
gender matched healthy normative data, available
in our lab.
2. To determine the correlation between IENFD and other outcome measures (SFN
symptom inventory questionnaire
(SIQ), mdCompass scale, EDSS, MRI, FSS, pain scales and HRQoL)
Secondary objectives are:
3. To examine the validity (correlation studies) and reliability (test-retest)
of the compass and SIQ in patients
with MS and autonomic dysfunction.
4. To examine the impact of health-related quality of life (HRQoL) in patients
with MS and autonomic dysfunction
versus patients with MS without autonomic complaints.
Study design
Patients with MS according to defined criteria will be eligible, and will be
divided into 3 groups, subgroup 1 (30 patients) with a relapsing-remitting
course, subgroup 2 (30 patients) with a secondary progressive course and
subgroup 3 (30 patients) with a primary progressive course. Each group is
divided into patients with patients with possible and without ANS dysfunction.
Possible ANS dysfunction and/or SFN is defined as at least one of the following
symptoms, not otherwise explained: burning pain in extremities, dry mouth or
eyes, changes in sweating, flushes, gastro-intestinal dysfunction (constipation
or diarrhoea), cardiac complaints (palpitation, dizziness at standing up),
uro-genital dysfunction (sexual dysfunction like impotence, incontinence).
The following outome measures will be applied:
* Skin biopsy for determination of IENF density
* Nerve conduction studies
* MRI brain and spinal cord.
* neurological examination (MRC sumscore, INCAT sensory sumscore, EDSS)
* A set of questionnaires will be completed: SFN screening list (SIQ),
mdCompass, VAS, PI-NRS, NPS, FSS, SF-36,
EuroQoL
Study burden and risks
The most important burden for patients will be time investment. Patients will
visit the hospital once. A skin biopsy is a routine diagnostic procedure and is
a minimal invasive procedure. There is a small risk of getting an infection and
most people get a small scar conform the size of the punch biopsy (3 mm).
Postbus 5500
6130 MB Sittard
NL
Postbus 5500
6130 MB Sittard
NL
Listed location countries
Age
Inclusion criteria
Inclusion criteria
- age: 18 years and older
- clinical definite MS according to the revised McDonald criteria.
- Brain MRI fulfilling the revised McDonald criteria.
- a clinical stable condition.
A clinical stable condition is defined as:
a) a clinical state without any new significant symptoms and/or signs as declared by the patient to the best of his/her knowledge
over 3 months prior to the study or
b) No clear objective changes at neurological examination by the researcher when compared with recorded findings over three
month before study entry (if available)
c) No methylprednisolone treatment within 3 months before study entry
- written informed consent
- patients should be ambulant (Expanded Disability Status Scale (EDSS) score of < 5.5). The latter was chosen to avoid possible IENFD reduction and autonomic impairments due to inactivity.
Exclusion criteria
- patients not meeting the inclusion criteria
- use ofmedication that would interfere with ANS assessment, or use of medication that is known to possibly cause peripheral neuropathy
- Other illnesses that might cause autonomic impairment (e.g., parkinson(ism), peripheral neuropathy, diabetes mellitus, alcohol abuse [arbitrarily defined as daily consumption of 5 IU or more], renal dysfunction, systemic illnesses)
Design
Recruitment
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 |
|---|---|
| CCMO | NL25959.096.09 |