Blood Biomarkers for Prognostic Stratification in Guillain-Barré Syndrome
Integration of a Blood Biomarker Panel for Prognostic Stratification in Guillain-Barré Syndrome: A Mexico-Spain Collaborative Study (BioGBS)
Guillain-Barré syndrome (GBS) is an acute immune-mediated peripheral neuropathy characterized by substantial variability in clinical severity, functional recovery, and pain outcomes. The lack of validated and accessible prognostic biomarkers limits early risk stratification and individualized rehabilitation strategies.
This observational, longitudinal, retrospective and prospective study aims to evaluate a panel of five blood biomarkers (EGR1, EGR2, GBP1, miR-29c, and Piccolo) and determine their association with functional recovery, pain trajectories, and neurophysiological characteristics in patients with GBS.
The study will include at least 70 patients with GBS and 70 healthy controls. Patients will undergo longitudinal clinical and molecular assessments across different disease stages, whereas healthy controls will provide a single blood sample for reference measurements. Gene and microRNA expression will be quantified using quantitative reverse transcription polymerase chain reaction (qRT-PCR), and serum Piccolo concentrations will be assessed using ELISA or validated immunoassays.
Clinical assessments will include the GBS Disability Scale, Medical Research Council (MRC) Sum Score, Functional Independence Measure (FIM), and validated pain questionnaires. Molecular and clinical data will be integrated using multivariable statistical analyses to identify prognostic molecular signatures and develop predictive models.
The project also aims to support external validation in Mexican populations through international collaboration with Spanish research institutions.
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Descrição detalhada
Guillain-Barré syndrome (GBS) is an acute immune-mediated polyradiculoneuropathy affecting the peripheral nervous system. It is characterized by heterogeneous clinical presentations, including progressive weakness, sensory disturbances, pain, autonomic dysfunction, and, in severe cases, respiratory failure. Although immunomodulatory treatments and multidisciplinary rehabilitation have improved clinical outcomes, predicting individual recovery trajectories remains challenging.
Current prognostic assessment relies primarily on clinical and electrophysiological parameters, which may not adequately capture the molecular mechanisms underlying immune activation, peripheral nerve injury, remyelination, and functional recovery.
Previous investigations conducted by the research group identified differential expression of EGR1, EGR2, GBP1, and miR-29c in peripheral blood mononuclear cells (PBMCs) obtained from patients with GBS. Differential serum concentrations of the presynaptic protein Piccolo were also identified, suggesting their potential relevance as molecular indicators of disease progression and recovery.
The BioGBS study aims to validate these five candidate biomarkers through longitudinal analysis and integration with clinical, functional, pain-related, and neurophysiological data.
The study will employ an observational, retrospective and prospective longitudinal design, including at least 70 patients diagnosed with GBS and 70 healthy controls. Patients will be assessed at four clinically defined stages: initial diagnosis before immunomodulatory treatment (T0), maximum clinical severity or nadir (T1), onset of sustained functional recovery (T2), and advanced recovery or discharge from rehabilitation (T3). Healthy controls will undergo a single baseline molecular assessment.
Gene expression levels of EGR1, EGR2, GBP1, and miR-29c will be quantified in PBMCs using qRT-PCR. Serum Piccolo concentrations will be determined using ELISA or validated immunoassays.
Functional outcomes will be assessed using the GBS Disability Scale, MRC Sum Score, and FIM. Pain severity and interference will be evaluated using the Brief Pain Inventory-Short Form (BPI-SF), while neuropathic pain will be assessed using the Neuropathic Pain Symptom Inventory (NPSI). Electrophysiological findings will be incorporated when available.
Statistical analyses will include longitudinal mixed-effects models, multivariable regression, principal component analysis, unsupervised clustering, and receiver operating characteristic curve analysis. Predictive models will be developed to identify molecular signatures associated with favorable or unfavorable functional recovery and persistent pain. Internal cross-validation and correction for multiple comparisons will be performed when appropriate.
The study will integrate the existing Spanish TOSGB biological collection and collaborative research activities in Mexico. External validation in Mexican patients is planned to evaluate the transferability of the prognostic biomarkers across different populations and healthcare settings.
No experimental treatment will be assigned. All participants with GBS will receive standard medical care and rehabilitation according to routine clinical practice.
Tipo de estudo
Inscrição (Estimado)
Contactos e Locais
Contato de estudo
- Nome: Antonio Ibarra, PhD
- Número de telefone: 52 5554197603
- E-mail: jose.ibarra@anahuac.mx
Locais de estudo
-
-
-
Toledo, Espanha
- Recrutamento
- Hospital Nacional de Parapléjicos
-
Contato:
- Ernesto Doncel Perez, PhD
- Número de telefone: 52 55 54197603
- E-mail: ernestod@sescam.jccm.es
-
-
-
-
-
Mexico City, México
- Recrutamento
- Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez
-
Contato:
- Antonio Ibarra, PhD
- Número de telefone: 52 5554197603
- E-mail: jose.ibarra@anahuac.mx
-
-
Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Método de amostragem
População do estudo
The study population will consist of patients aged 16 years or older with clinically and neurophysiologically confirmed Guillain-Barré syndrome, recruited from participating hospitals in Spain and Mexico. A comparison group of healthy volunteers aged 18 years or older, with a comparable age and sex distribution, will be included to establish reference biomarker measurements. Patients will undergo longitudinal follow-up, whereas healthy controls will undergo a single baseline assessment.
Descrição
Inclusion Criteria:
- Diagnosis of Guillain-Barré syndrome based on clinical and neurophysiological criteria.
- Age 16 years or older.
- Availability of biological samples for molecular analysis.
- Written informed consent.
- Availability of longitudinal clinical data.
Exclusion Criteria:
- Alternative diagnosis explaining the neurological manifestations.
- Concomitant active autoimmune disease.
- Severe systemic infection.
- Previous unrelated immunosuppressive treatment.
- Incomplete clinical data or absence of informed consent.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Modelos de observação: COHORT
- Perspectivas de Tempo: OTHER
Coortes e Intervenções
Grupo / Coorte |
Intervenção / Tratamento |
|---|---|
|
Patients With Guillain-Barré Syndrome
Patients with clinically and neurophysiologically confirmed GBS undergoing longitudinal molecular, functional, pain-related, and neurophysiological assessments across different stages of the disease. |
Peripheral blood samples will be collected from patients with Guillain-Barré syndrome and healthy controls to evaluate a panel of molecular biomarkers. Expression levels of EGR1, EGR2, GBP1, and miR-29c will be quantified in peripheral blood mononuclear cells using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Serum Piccolo concentrations will be measured using ELISA or validated immunoassays. Patients with Guillain-Barré syndrome will undergo longitudinal assessments at predefined clinical stages, whereas healthy controls will undergo a single baseline assessment. No experimental treatment will be administered, and routine clinical management will remain unchanged. |
|
Healthy Controls
Healthy individuals without neurological or autoimmune disorders, selected to provide reference measurements for the candidate blood biomarkers. Controls will undergo a single baseline blood sample collection. |
Peripheral blood samples will be collected from patients with Guillain-Barré syndrome and healthy controls to evaluate a panel of molecular biomarkers. Expression levels of EGR1, EGR2, GBP1, and miR-29c will be quantified in peripheral blood mononuclear cells using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Serum Piccolo concentrations will be measured using ELISA or validated immunoassays. Patients with Guillain-Barré syndrome will undergo longitudinal assessments at predefined clinical stages, whereas healthy controls will undergo a single baseline assessment. No experimental treatment will be administered, and routine clinical management will remain unchanged. |
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Change in Guillain-Barré Syndrome Disability Score
Prazo: Baseline (Day 1), up to 6 months, and up to 12 months after baseline
|
Change in functional disability measured using the GBS Disability Scale, ranging from 0 (normal health) to 6 (death). Higher scores indicate greater disability. Longitudinal changes will be assessed in relation to blood biomarker expression. 0 (Baseline): Day 1, before initiation of immunotherapy. T1 (Nadir or prolonged plateau): Up to 6 months after baseline. T2 (Onset of clinical recovery): Up to 12 months after baseline. T3 (Advanced recovery or neurorehabilitation discharge): Up to 12 months after baseline. All assessment intervals are calculated from T0 (baseline). Clinical stages are determined according to the patient's disease progression and recovery status. |
Baseline (Day 1), up to 6 months, and up to 12 months after baseline
|
|
Change in Muscle Strength Assessed by the MRC Sum Score
Prazo: Baseline (Day 1), up to 6 months, and up to 12 months after baseline.
|
Change in muscle strength assessed using the Medical Research Council Sum Score, ranging from 0 to 60. Higher scores indicate better muscle strength. Longitudinal changes will be evaluated in association with molecular biomarker profiles. T0 (Baseline): Day 1, before initiation of immunotherapy. T1 (Nadir or prolonged plateau): Up to 6 months after baseline. T2 (Onset of clinical recovery): Up to 12 months after baseline. T3 (Advanced recovery or neurorehabilitation discharge): Up to 12 months after baseline. |
Baseline (Day 1), up to 6 months, and up to 12 months after baseline.
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Change in Functional Independence Measure Score
Prazo: Baseline (Day 1), up to 6 months, and up to 12 months after baseline.
|
Functional independence measured using the Functional Independence Measure (FIM), ranging from 18 to 126. Higher scores indicate greater independence in activities of daily living. T0 (Baseline): Day 1, before initiation of immunotherapy. T1 (Nadir or prolonged plateau): Up to 6 months after baseline. T2 (Onset of clinical recovery): Up to 12 months after baseline. T3 (Advanced recovery or neurorehabilitation discharge): Up to 12 months after baseline. |
Baseline (Day 1), up to 6 months, and up to 12 months after baseline.
|
|
Change in Pain Intensity Assessed by the Brief Pain Inventory
Prazo: Baseline (Day 1), up to 6 months, and up to 12 months after baseline.
|
Change in pain intensity measured using the Brief Pain Inventory-Short Form (BPI-SF), on a scale from 0 to 10, with higher scores indicating greater pain intensity. T0 (Baseline): Day 1, before initiation of immunotherapy. T1 (Nadir or prolonged plateau): Up to 6 months after baseline. T2 (Onset of clinical recovery): Up to 12 months after baseline. T3 (Advanced recovery or neurorehabilitation discharge): Up to 12 months after baseline. |
Baseline (Day 1), up to 6 months, and up to 12 months after baseline.
|
|
Change in Pain Interference Assessed by the Brief Pain Inventory
Prazo: Baseline (Day 1), up to 6 months, and up to 12 months after baseline.
|
Change in the interference of pain with daily activities, measured using the BPI-SF on a scale from 0 to 10, with higher scores indicating greater interference. T0 (Baseline): Day 1, before initiation of immunotherapy. T1 (Nadir or prolonged plateau): Up to 6 months after baseline. T2 (Onset of clinical recovery): Up to 12 months after baseline. T3 (Advanced recovery or neurorehabilitation discharge): Up to 12 months after baseline. |
Baseline (Day 1), up to 6 months, and up to 12 months after baseline.
|
|
Change in Neuropathic Pain Symptom Inventory Score
Prazo: Baseline (Day 1), up to 6 months, and up to 12 months after baseline.
|
Change in neuropathic pain symptoms assessed using the Neuropathic Pain Symptom Inventory (NPSI), with a total score ranging from 0 to 100. Higher scores indicate greater neuropathic pain severity. T0 (Baseline): Day 1, before initiation of immunotherapy. T1 (Nadir or prolonged plateau): Up to 6 months after baseline. T2 (Onset of clinical recovery): Up to 12 months after baseline. T3 (Advanced recovery or neurorehabilitation discharge): Up to 12 months after baseline. |
Baseline (Day 1), up to 6 months, and up to 12 months after baseline.
|
|
Longitudinal Change in EGR1, EGR2, GBP1, and miR-29c Expression
Prazo: Baseline (Day 1), up to 6 months, and up to 12 months after baseline.
|
Relative expression of EGR1, EGR2, GBP1, and miR-29c in PBMCs measured using qRT-PCR and expressed as 2^-ΔCt or 2^-ΔΔCt. Associations with clinical recovery trajectories will be analyzed. T0 (Baseline): Day 1, before initiation of immunotherapy. T1 (Nadir or prolonged plateau): Up to 6 months after baseline. T2 (Onset of clinical recovery): Up to 12 months after baseline. T3 (Advanced recovery or neurorehabilitation discharge): Up to 12 months after baseline. |
Baseline (Day 1), up to 6 months, and up to 12 months after baseline.
|
|
Longitudinal Change in Serum Piccolo Concentration
Prazo: Baseline (Day 1), up to 6 months, and up to 12 months after baseline.
|
Serum Piccolo concentration quantified using ELISA or a validated immunoassay and expressed in pg/mL or ng/mL, depending on assay specifications. T0 (Baseline): Day 1, before initiation of immunotherapy. T1 (Nadir or prolonged plateau): Up to 6 months after baseline. T2 (Onset of clinical recovery): Up to 12 months after baseline. T3 (Advanced recovery or neurorehabilitation discharge): Up to 12 months after baseline. |
Baseline (Day 1), up to 6 months, and up to 12 months after baseline.
|
|
Prognostic Performance of the Combined Blood Biomarker Panel
Prazo: Baseline (Day 1), up to 6 months, and up to 12 months after baseline.
|
Discriminative performance of a combined panel comprising EGR1, EGR2, GBP1, miR-29c, and Piccolo for identifying unfavorable functional recovery, evaluated using the area under the receiver operating characteristic curve (AUC). T0 (Baseline): Day 1, before initiation of immunotherapy. T1 (Nadir or prolonged plateau): Up to 6 months after baseline. T2 (Onset of clinical recovery): Up to 12 months after baseline. T3 (Advanced recovery or neurorehabilitation discharge): Up to 12 months after baseline. |
Baseline (Day 1), up to 6 months, and up to 12 months after baseline.
|
|
Requirement for Mechanical Ventilation
Prazo: From baseline (Day 1) through 12 months after baseline.
|
Proportion of patients requiring invasive mechanical ventilation during the acute phase of GBS and duration of ventilatory support when applicable. |
From baseline (Day 1) through 12 months after baseline.
|
Colaboradores e Investigadores
Patrocinador
Colaboradores
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Estimado)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
- Distúrbios pós-infecciosos
- Doenças do Sistema Nervoso
- Processos Patológicos
- Doenças Neuromusculares
- Doença crônica
- Atributos da doença
- Doenças autoimunes
- Doenças do sistema imunológico
- Doenças do Sistema Nervoso Periférico
- Doenças Autoimunes do Sistema Nervoso
- Doenças Desmielinizantes
- Polineuropatias
- Polirradiculoneuropatia
- Condições Patológicas, Sinais e Sintomas
- A síndrome de Guillain-Barré
Outros números de identificação do estudo
- 241/2018
Informações sobre medicamentos e dispositivos, documentos de estudo
Estuda um medicamento regulamentado pela FDA dos EUA
Estuda um produto de dispositivo regulamentado pela FDA dos EUA
Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .