The International GBS Outcome Study (IGOS) aims to identify the most important clinical and biological determinants of disease progression and recovery in GBS. This information will be used to understand the diversity in clinical presentation and…
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Source
Brief title
Condition
- Autoimmune disorders
- Infections - pathogen unspecified
- Peripheral neuropathies
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
IGOS will result in a large combined clinical database and biobank of patients
with GBS with all the variants and subtypes. Expertise Groups will use this
data/biobank to determine the processes that determine and predicts disease
progression and recovery in GBS. This information will be used to develop
predictive models that can predict the clinical course in individual patients
with GBS. These prognostic models can guide selective therapeutic trails in the
future with specific subtypes of patients to personalize the treatment and
improve the prognosis of GBS. The main outcome measures for the clinical course
are the GBS disability score, MRC sum score, Overall Neuropathy Limitations
Scale (ONLS), Rasch-built Overall Disability Scale(R-ODS), Fatigue Severity
Scale(FSS) en EurQoL.
For children (IGOS-kids) the following outcome measures will be: GBS disability
score, MRC sum score, GBS-kids score, Peds-QL, Peds-QL MFS, ACTIVLIM, FSS and
ONLS dependent of the age of the patient. (See supplement 19 of the protocol)
IGOS will be divided in expertise groups that will focus on specific research
areas, including:
• Prognostic modelling : development of models to predict
clinical course and outcome
• Treatment interventions : defining treatment practice,
effects and side-effects
• Pharmacokinetics of IVIg : defining serum IgG levels after IVIg in relation
to outcome
• Electrophysiology : prognostic relevance of electrophysiological
classification
• Preceding events : defining type of infections/vaccinations related to GBS
and outcome
• Anti-neural antibodies : characterisation of serum
antibodies related to GBS and outcome
• CSF biomarkers : proteomic studies of CSF in relation to GBS and outcome
• Genetic markers : genetic studies to define polymorphisms related to GBS
and outcome
• Paediatric GBS : characterisation of clinical course and outcome in
children with GBS (IGOS-Kids)
• Long-term outcome : residual disability and impact 2 and
3 years after disease onset
• Outcome measures : development of clinical outcome measures to monitor GBS
Secondary outcome
Besides the above clinical outcome measures IGOS will investigate several other
GBS-related clinical effects, including autonomic dysfunction, and transition
to chronic inflammatory demyelinating polyneuropathy.
Background summary
The only proven effective forms of treatment for GBS are intravenous
immunoglobulins and plasma exchange. Despite these partially effective forms of
treatment, outcome in patients with Guillain-Barré syndrome (GBS) has not
improved in the last two decades. At present about 10 to 20% of patients remain
severely disabled and about 5% die. One explanation for this stagnation is the
highly variable clinical course of GBS and the lack of knowledge about the
factors that determine the clinical course in individual patients with GBS. GBS
may consist of distinct pathogenic subgroups, in which disease onset and
progression is influenced by different types of preceding infections,
anti-neural antibodies and genetic polymorphisms. Optimal treatment of
individual patients may depend on the pathogenesis and clinical severity.
Patients with severe forms of GBS may possibly need more intensive treatment to
recover. Patients with a milder course that fully recover after standard
therapy could suffer from possibly more side effects of more aggressive forms
of treatment. The aim is therefore to reserve additional treatment for patients
with a poor prognosis. This could only be possible if there are prognostic
models that accurately predict the clinical course in individual patients.
Ideally such models should be based on clinical and biological predictors that
are strongly associated with disease course and known as early as possible in
the acute phase of illness, when treatment with immunomodulatory therapy is
most effective. Prognostic models could help to guide selective trials in
specific GBS subtypes. Because of this it will be possible to treat GBS with
more effective and more individual therapy. Previous studies indicate that
outcome in GBS depends on a defined set of clinical, laboratory and
electrophysiological features. An example of such a prognostic model is the
Erasmus GBS outcome score (EGOS), which is based on three clinical
characteristics: age, presence of preceding diarrhoea, and GBS disability score
at two weeks after admission. The EGOS accurately predicts the chance of
walking after six months. Additional prognostic models have been developed to
predict the chance on respiratory insufficiency. Biomarkers related to clinical
course and outcome have also been identified in GBS, including
electrophysiological characteristics, type of preceding infection, serum
anti-ganglioside antibodies, genetic polymorphisms, and mediators of
inflammation. Most of these prognostic studies were retrospective and based on
a small number of patients and a limited set of outcome measures. Further
research is required to define which determinants can be used for early
identification of patients with poor prognosis. At present we don*t know much
about the factors that influence the process of nerve damaging and regeneration
in GBS. To address these research questions it is required to conduct a
prospective study with standardized collection of clinical data and
biomaterials from a large group of well-defined GBS patients during a long
follow-up period. Such an extensive study in a relatively rare disease as GBS
can be addressed only by intensive international collaboration.
Study objective
The International GBS Outcome Study (IGOS) aims to identify the most important
clinical and biological determinants of disease progression and recovery in
GBS. This information will be used to understand the diversity in clinical
presentation and response to treatment of GBS. This information will also be
used to develop new prognostic models to predict the clinical course and
outcome accurately in individual patients with GBS.
Study design
IGOS is a prospective observational international multi-centre study including
at least 1000 patients with GBS or variants of GBS, including the Miller Fisher
syndrome (MFS) and overlap syndromes. The study has a follow-up of one year,
with the option to extend this period to two and three years. IGOS will lead to
a detailed and standardised database with data about clinical course,
treatment, and the results of the standard evaluation of GBS patients
(electrophysiological data and liquor). In addition, the IGOS will result in a
biobank linked to the database in which DNA and serial serum samples are
collected. In the IGOS there is also an option (1) to collect cerebrospinal
fluid during routine diagnostic work-up, and (2) conducting a more extensive
follow-up of two and three years.
Study burden and risks
GBS patients are generally for a long time in the hospital, where they will
undergo venapunctures and physical examination regularly in the initial phase.
After discharge from hospital they will frequently be seen again in the
outpatient clinic to assess the amount of recovery. This is all part of
standard medical work-up for patients with GBS. In IGOS this medical work-up
will be standardized and data will be retained for further research. In IGOS we
try to combine this as much as possible with the standard clinical care and
medical work-up. Besides the regular clinical care we will also collect
clinical data, questionnaires and blood samples at 6 to 8 standard times. A
venapuncture has a very small risk of formation of hematoma and infection. The
majority of GBS patients will undergo an EMG or a lumbar puncture as part of
the standard diagnostics. Only in these patients, these data will be collected
for the IGOS. If no lumbar puncture or EMG was performed for various reasons,
no lumbar puncture will be performed in the scope of this study. In patients
that undergo a routine diagnostic lumbar puncture, there is a possibility to
collect additional 2 ml of CSF for further research when the patient consents.
Collection of these 2 ml extra results in no additional risks or discomfort.
Furthermore, it is possible to expand the follow up to 2 and 3 year, only when
the patient consents. This will result in extra questionnaires (by telephone).
So for this study the risks are negligible.
Wytemaweg 80
Rotterdam 3015 CN
NL
Wytemaweg 80
Rotterdam 3015 CN
NL
Listed location countries
Age
Inclusion criteria
Criteria for inclusion of patients in the IGOS:
• Fulfil the diagnostic criteria for GBS of the National Institute of
Neurological Disorders and Stroke (NINDS). In addition all patients with Miller
Fisher syndrome (MFS) and other variants of GBS, including overlap syndromes
can be included, for which additional diagnostic criteria will be provided.
• Inclusion of all males and females of all ages, independent of disease
severity and treatment
• Inclusion within two weeks of onset of weakness. In IGOS-Kids, children
should be included within four weeks of onset of weakness. In IGOS-Infections,
patients should be included within 8 weeks after onset of weakness.
• Inclusion of patients transferred from another hospital if the stay in the
first hospital was less than one week. In IGOS-Infections patients can still be
included if the stay in another hospital was more than one week.
• Opportunity to conduct a follow-up of at least one year. In IGOS-Infections
and IGOS-Zika opportunity to follow-up at least 6 months.
• In IGOS-Infections: suspected antecedent infection related to GBS.
• Informed consent of the patient or, in case of children, of the parents or
legal guardiansCriteria for inclusion of patients in the optional research
modules of the IGOS: Additional informed consent is required for each optional
research module:
(1) CSF biomarkers: additional volume obtained at diagnostic spinal tap
(2) Long-term outcome: additional clinical assessments at two and three years
gelijk n
Exclusion criteria
No exclusion criteria
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
Register | ID |
---|---|
CCMO | NL38706.078.11 |
OMON | NL-OMON22932 |