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

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

1. study the pharmacokinetics of mini-pooled intravenous immunoglobulin( MP-IVIG)

2. 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:

     1. Patient able to walk
     2. Improvement of general health.
     3. Integration in to social live
3. to compare the efficacy of IVIg to plasma exchange (PE) in hastening recovery and improving the condition of GBS

Study Overview

• Status: Unknown
• Conditions: Guillain-Barre Syndrome
• Intervention / Treatment: Other: Mini-pool Intravenous Immunoglobulin (MP-IVIG); Other: plasma exchange

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hend A Moubark, Specialist; Phone Number: 01010326577; Email: hindq1989@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Mini-pool Intravenous Immunoglobulin (MP-IVIG); 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); 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.
EXPERIMENTAL: plasmapheresis; 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; 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 Names: plasmapheresis

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Assiut University
• Investigators: Study Director: Maha A Mohamed, Prof, Assiut University

Publications and helpful links

General Publications

• El-Ekiaby M, Sayed MA, Caron C, Burnouf S, El-Sharkawy N, Goubran H, Radosevich M, Goudemand J, Blum D, de Melo L, Soulie V, Adam J, Burnouf T. Solvent-detergent filtered (S/D-F) fresh frozen plasma and cryoprecipitate minipools prepared in a newly designed integral disposable processing bag system. Transfus Med. 2010 Feb;20(1):48-61. doi: 10.1111/j.1365-3148.2009.00963.x. Epub 2009 Sep 23.
• van Doorn PA, Ruts L, Jacobs BC. Clinical features, pathogenesis, and treatment of Guillain-Barre syndrome. Lancet Neurol. 2008 Oct;7(10):939-50. doi: 10.1016/S1474-4422(08)70215-1.
• El-Ekiaby M, Vargas M, Sayed M, Gorgy G, Goubran H, Radosevic M, Burnouf T. Minipool caprylic acid fractionation of plasma using disposable equipment: a practical method to enhance immunoglobulin supply in developing countries. PLoS Negl Trop Dis. 2015 Feb 26;9(2):e0003501. doi: 10.1371/journal.pntd.0003501. eCollection 2015 Feb.
• Winiecki S, Baer B, Chege W, Jankosky C, Mintz P, Baker M, Woodworth T, Nguyen M. Complementary use of passive surveillance and Mini-Sentinel to better characterize hemolysis after immune globulin. Transfusion. 2015 Jul;55 Suppl 2:S28-35. doi: 10.1111/trf.13116.
• Ojha R, Karn R(2019):Clinical outcome of intravenous immunoglobulin in the treatment of Guillain Barre Syndrome in a Nepalese tertiary centre. Nep Med J 2019;2(1):133-7.
• Hughes RA, Cornblath DR. Guillain-Barre syndrome. Lancet. 2005 Nov 5;366(9497):1653-66. doi: 10.1016/S0140-6736(05)67665-9.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): November 1, 2021
• Primary Completion (ANTICIPATED): November 1, 2022
• Study Completion (ANTICIPATED): December 1, 2022

Study Registration Dates

• First Submitted: August 27, 2020
• First Submitted That Met QC Criteria: September 9, 2020
• First Posted (ACTUAL): September 16, 2020

Study Record Updates

• Last Update Posted (ACTUAL): January 14, 2021
• Last Update Submitted That Met QC Criteria: January 12, 2021
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Disease; Neuromuscular Diseases; Peripheral Nervous System Diseases; Polyradiculoneuropathy; Polyneuropathies; Syndrome; Guillain-Barre Syndrome; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Immunoglobulins; Immunoglobulins, Intravenous; gamma-Globulins; Rho(D) Immune Globulin
• Other Study ID Numbers: Guillain-Barré syndrome

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No