Mini-pool Intravenous Immunoglobulin (MP-IVIG) in Guillain-Barré Syndrome

Study Overview
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Brief Summary
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study the pharmacokinetics of mini-pooled intravenous immunoglobulin( MP-IVIG) to determine the efﬁcacy of intravenous immunoglobulin (IVIg) in hastening recovery and reducing the complications of Guillain-Barré syndrome (GBS). The MP-IVIG was tolerated and presented no safety issues in a previous study and we will be confirmed by monitoring any adverse events (anaphylaxis and haemolysis) ( no or mild or moderate) and reporting them to ethical committee safety monitoring group. Efficacy will be confirmed by: Patient able to walk Improvement of general health. Integration in to social live to compare the efﬁcacy of IVIg to plasma exchange (PE) in hastening recovery and improving the condition of GBS

Detailed Description
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Guillain-Barré syndrome (GBS) is a frequent cause of neuromuscular paralysis occurring at all ages. The incidence of GBS is reported to be 1.2-2.3 per 100,000 per year . GBS is a post infectious disorder. The most frequently identified preceding infection is Campylobacter jejuni. Others are cytomegalovirus, Epstein-Barr virus, Mycoplasma pneumoniae, and Haemophilus influenzae . Many reports have documented the occurrence of GBS shortly after vaccinations, operations, or stressful events, but the causality and pathophysiology are still debated . Rapidly progressive weakness is the core clinical feature of GBS. By definition, maximal weakness is reached within 4 weeks, but most patients reach it within 2 to 3 weeks. Thereafter, patients enter a plateau phase that ranges from days to several weeks or months . This phase is followed by a usually much slower and variable recovery phase. In Europe, about one-third of GBS patients remain able to walk (mild patients) .about 25% of the GBS patients who are unable to walk (severe patients) need artificial ventilation. This is predominantly due to weakness of the respiratory muscles. GBS has a great impact on social life and the ability to perform activities of daily life. therefore, GBS remains a severe disease for which better treatments are required . . Magdy EL-Ekiaby, et al 2010 introduce the concept of small-scale (minipool) plasma processing methods. The preparation of the Immunoglobulin G (IgG) plasma fractionation from 20 blood donations which are tested for anti-A and anti-B titre < 32. Implementable with minimum infrastructural requirements. They developed viral inactivation and protein purification technologies in single-use equipment to prepare virally safe solvent/detergent-filtered (S/D-F) plasma Producing a 90%pure immunoglobulin fraction in disposable single-use devices for transfusion . IVIG adverse events (AEs) are not frequent; hemolysis after IVIG is a known, rare complication. Higher doses and non-O blood group are key risk factors. The incidence of post-IVIG hemolysis is estimated at 1 per 1000 IVIG treatment episodes, most of which occur within 2 days of exposure. Although the preparation of blood group specific IVIGs in industry is a complex issue because of the pooling of thousands of plasma donations per batch, the preparation of blood group-specific mini-pool IVIG (MP-IVIG) is possible because each pool consists of only 20 plasma donations. Blood group-matched MP-IVIG is assumed to reduce the incidence of IVIG-associated hemolysis, which is largely caused by the presence of anti-A and anti-B agglutinins reacting with non-O blood group recipients.

Official Title
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Efficacy of Mini-pool Intravenous Immunoglobulin (MP-IVIG) Prepared by Assiut University Hospital Blood Bank in Guillain-Barré Syndrome

Conditions
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Guillain-Barre Syndrome

Intervention / Treatment
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* Other: Mini-pool Intravenous Immunoglobulin (MP-IVIG)
* Other: plasma exchange


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age group: 18-40 years. Both sex are include The study will include patient diagnosed as Guillain-Barré syndrome (mild) cases in neuropsychiatric hospital at Assiut university hospitals. Exclusion Criteria: • Patient has severe form of Guillain-Barré syndrome (GBS) according to GBS disability score Patient with renal impairment Patient with hepatic cell failure

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The process of MP-IVIG preparation will involve the use of caprylic acid for purification and virus inactivation of Igs from mini-pools of 20 plasma donations collected in our Central blood transfusions( CBTS) in Assiut University Hospital (AUH). The equipment used for the process comprised disposable blood bags, hemodialyzers, and purification and microbial filters.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mini-pool Intravenous Immunoglobulin (MP-IVIG)<br>will receive blood group -specific MP-IVIG in a regimen of 2 g/kg bodyweight, usually as 0.4 g/kg bodyweight per day for five consecutive days within two weak of onset of symptoms. | Other: Mini-pool Intravenous Immunoglobulin (MP-IVIG)<br>* The process of MP-IVIG preparation will involve the use of caprylic acid for purification and virus inactivation of Igs from mini-pools of 20 plasma donations collected in our CBTS in AUH. The equipment used for the process comprised disposable blood bags, hemodialyzers, and purification and microbial filters.<br>|
| Experimental: plasmapheresis<br>plasma exchange (plasmapheresis ) in a regimen of removing of 1.3 plasma volumes in each cycle for total of five cycle for five consecutive days within four weeks of onset of symptoms. | Other: plasma exchange<br>* plasma exchange (plasmapheresis ) in a regimen of removing of 1.3 plasma volumes in each cycle for total of five cycle for five consecutive days within four weeks of onset of symptoms.<br>* Other names: plasmapheresis;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy ofMini-pool Intravenous Immunoglobulin (MP-IVIG) assessed by patients achieve score more than or equal 2 according to GBS disability score | Guillain-Barré syndrome disability scale Score Description 0 A healthy state Minor symptoms and capable of running Able to walk 10m or more without assistance but unable to run Able to walk 10m across an open space with help Bedridden or chairbound Requiring assisted ventilation for at least part of the day Dead | 6 MONTHS | 
| Safety of MP-IVIG assessed by percentage of adverse Events: Overall percentage of adverse events | Overall percentage of adverse events as hemolysis and anaphylaxis headache and other complains that occur during 72 hours of following an infusion of MP-IVIG will be assessed by1) vital sign(pulse,blood pressure,Respiratory rate and temperature 2)Hemolysis by hemoglobin level, Lactate dehydrogenase( LDH),bilirubin level.2)between infusions by home diaries. | 72 hour after adminstration of MP-IVIG and between infusions period | 
| Study the pharmacokinetics- MP-IVIG trough levels | MP-IVIG trough level concentration values of serum total IgG pre the MP-IVIG infusion (if applicable). | predose sample | 
| Study the pharmacokinetics MP-IVIG plasma concentration -time curve [ | Blood samples for analysis of pharmacokinetics MP-IVIG plasma concentration -time curve were obtained and analysed Blood samples for analysis of pharmacokinetics MP-IVIG plasma concentration -time curve were obtained and analysed | (1 hour, 2 hours and 1, 2, 3, 7, 14 and 21 days) post-dose ] | 
| Study the pharmacokinetics MP-IVIG half-life | Blood samples for analysis of pharmacokinetics MP-IVIG haf-life were obtained and analysed | (1 hour, 2 hours and 1, 2, 3, 7, 14 and 21 days) post-dose ] | 
| Study the pharmacokinetics MP-IVIG area under the curve | Blood samples for analysis of pharmacokinetics MP-IVIG haf-life were obtained and analysed | (1 hour, 2 hours and 1, 2, 3, 7, 14 and 21 days) post-dose ] | 
| Study the pharmacokinetics MP-IVIG Cmax | Blood samples for analysis of pharmacokinetics MP-IVIG Cmax were obtained and analysed | (1 hour, 2 hours and 1, 2, 3, 7, 14 and 21 days) post-dose ] | 
| Study the pharmacokinetics of MP-IVIG-Tmax. | Blood samples for analysis of pharmacokinetics MP-IVIG Tmax were obtained and analysed | (1 hour, 2 hours and 1, 2, 3, 7, 14 and 21 days) post-dose ] | 
| Study the pharmacokinetics of MP-IVIG elimination rate constant(s). : ( | Blood samples for analysis of pharmacokinetics MP-IVIG elimination rate constant(s) were obtained and analysed | 1 hour, 2 hours and 1, 2, 3, 7, 14 and 21 days) post-dose ] | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| • compare the efﬁcacy of IVIg to plasma exchange (PE) according to GBS disability score | Guillain-Barré syndrome disability scale Score Description 0 A healthy state Minor symptoms and capable of running Able to walk 10m or more without assistance but unable to run Able to walk 10m across an open space with help Bedridden or chairbound Requiring assisted ventilation for at least part of the day Dead | 6 MONTHS |