Gullian Barre Syndrome Clinical Trial
— ICA-GBSOfficial title:
Inhibition of Complement Activation (Eculizumab) in Guillain-Barre Syndrome Study
Guillian-Barre Syndrome (GBS) is the most frequent cause of acute neuromuscular weakness in
the Western World and can occur at any age. GBS is a rpadily progressive 'inflammatory'
disorder of the perihperal nerves often leading to sever paresis of the limbs. Most GBS
patients also have sensory disturbances (tingling or dull feeling) and pain. Some patients
also have double vision or problems with swallowing. GBS mau also involve the respiratory
muscles, leading to insufficient ventilation and admission to an intensive care unit. GBS
pateints have a vairable prognosis; 20-30% require mechnical ventilation for a period
ranging from weeks to months, 20% are unable to walk after 6 months nad 3-5% dies.
Progression of weakness in GBS is usually rapid and reaches its peak within 4 weeks in the
majority of patients, but many develop their maximum deficit within 2 weeks. Thereafter, the
patients have a variable prognosis.
GBS is a treatable disorder. Intravenous immunoglobulin (IVIg) 2g/kg administered in 5 days
was shown to be effective when administered within the first two weeks after onset of
symptoms, and is considered the treatment of choice by most experts in the field. Although
the standard treatment for GBS is a single course of IVIg (2g/kg administered in 5 days),
many patients fails to recover abd remain with substantial disability. Patients with GBS and
especially those with a poor prognosis potentially may benefit from more powerful abd when
possible a more mechanistically rational therapy.
Recent experimental evidence suggests that complement activation palys a crucial role in the
development of neuromuscular weakness in GBS making complement inhibitors and regulators
attracive therapeutic targets. Our hypothesis is that Eculizumab, with its function as a
complement inhibitor, will be very effective in preventing progression of weakness in
patients with GBS.
| Status | Recruiting |
| Enrollment | 30 |
| Est. completion date | March 2016 |
| Est. primary completion date | October 2015 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 18 Years and older |
| Eligibility |
Inclusion Criteria: - Patients aged >18 years diagnosed with GBS according to NINDS diagnostic criteria - Onset of weakness due to GBS is less than 2 weeks ago - Patients who are unable to walk unaided for >10 metres (grade >3 on GBS disability scale) - Patients who are being considered for or already on IVIg treatment - First dose of eculizumab must be started within 2 weeks from onset of weakness and any time during the IVIg treatment period - Signed informed consent Exclusion Criteria: - Age <18 years - Patients who are being considered for, or already on, plasma exchange - Pregnancy or lactation - Patients show clear clinical evidence of a polyneuropahty caused by e.g. diabetes mellitus (except mild sensory), alcoholism, severe vitamin deficiency, and porphyria - Patients received immunosuppressive treatment (e.g. azathioprine, cyclosporine, mycofenolatemofetil, tacrolimus, sirolimus or > 20 mg prednisolone daily) during the last month - Patients known to have severe concurrent disease, like malignancy, severe cardiovascular disease, AIDS, severe COPD, TB - Inability to comply with study related procedures or appointments during 6 months - Any condition that in the opinion of the investigator could increase the patient's risk by participating in the study or confound the outcome of the study - Related to the administration of eculizumab: Unresoled Neisseria meningitidisinfection of history of meningococcal infection Unsuitable for antibiotic prophylaxis (e.g due to allergy) Known hypersensitivity to eculizumab, murine proteins or to any of the excipients Known or suspected hereditary complement deficiencies Women of child-bearing potential who are unwilling to use effective contraception during treatment and for 5 months after treatment is completed. |
Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| United Kingdom | Southern General Hospital | Glasgow |
| Lead Sponsor | Collaborator |
|---|---|
| NHS Greater Glasgow and Clyde | University of Glasgow |
United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Determine the incidence of AE/SAEs after treatment with eculizumab and IVIg compared to placebo controls | Primary safety endpoint | 6 months | Yes |
| Primary | Improvement of one or more grade in functional outcome (on the 6 point GBS disability scale) at 4 weeks | Primary efficacy endpoint | 4 weeks | No |
| Secondary | Ability to walk unaided (GBS disability score 2) at 8 weeks | 8 weeks | No | |
| Secondary | Time taken to improve by at least one grade (on the GBS disability scale) | 8 weeks | No | |
| Secondary | Time taken to walk independently | 1 year | No | |
| Secondary | Difference in GBS disability score at maximum disability completed with 6 months | 6 months | No | |
| Secondary | Percentage of patients with a clinically relevant improvement in R-ODS score | An increase from Baseline in R-ODS score by at least 6 points on the centile metric score at 4 weeks and 6 months | 6 months | No |
| Secondary | Percentage of patients with a clinically relevant improvement in ONLS | Defined as an increase from baseline in ONLS score by at least 1 point at 4 weeks and 6 months | 6 months | No |
| Secondary | Requirement for ventilatory support (GBS disability score 5) | 4 weeks | No | |
| Secondary | Duration of ventilatory support | 8 weeks | No | |
| Secondary | Occurrence of relapse | 2 years | No | |
| Secondary | Dearth within the first 6 months | 6 months | No |