Clinical trial NCT04550611: Mini-pool Intravenous Immunoglobulin (MP-IVIG) in Guillain-Barré Syndrome
Official title: Efficacy of Mini-pool Intravenous Immunoglobulin (MP-IVIG) Prepared by Assiut University Hospital Blood Bank in Guillain-Barré Syndrome
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Guillain-Barre Syndrome
Lead sponsor: Assiut University
Sponsor class: OTHER
First posted: 2020-09-16
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

Brief summary: 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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Efficacy ofMini-pool Intravenous Immunoglobulin (MP-IVIG) assessed by patients achieve score more than or equal 2 according to GBS disability score
timeFrame: 6 MONTHS
measure: Safety of MP-IVIG assessed by percentage of adverse Events: Overall percentage of adverse events
timeFrame: 72 hour after adminstration of MP-IVIG and between infusions period
measure: Study the pharmacokinetics- MP-IVIG trough levels
timeFrame: predose sample
measure: Study the pharmacokinetics MP-IVIG plasma concentration -time curve [
timeFrame: (1 hour, 2 hours and 1, 2, 3, 7, 14 and 21 days) post-dose ]
measure: Study the pharmacokinetics MP-IVIG half-life
timeFrame: (1 hour, 2 hours and 1, 2, 3, 7, 14 and 21 days) post-dose ]
measure: Study the pharmacokinetics MP-IVIG area under the curve
timeFrame: (1 hour, 2 hours and 1, 2, 3, 7, 14 and 21 days) post-dose ]
measure: Study the pharmacokinetics MP-IVIG Cmax
timeFrame: (1 hour, 2 hours and 1, 2, 3, 7, 14 and 21 days) post-dose ]
measure: Study the pharmacokinetics of MP-IVIG-Tmax.
timeFrame: (1 hour, 2 hours and 1, 2, 3, 7, 14 and 21 days) post-dose ]
measure: Study the pharmacokinetics of MP-IVIG elimination rate constant(s). : (
timeFrame: 1 hour, 2 hours and 1, 2, 3, 7, 14 and 21 days) post-dose ]
Secondary outcomes:
measure: • compare the efﬁcacy of IVIg to plasma exchange (PE) according to GBS disability score
timeFrame: 6 MONTHS
Other outcomes:
Locations:
Study officials:
affiliation: Assiut University
name: Maha A Mohamed, Prof
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: Hughes RA, Cornblath DR. Guillain-Barre syndrome. Lancet. 2005 Nov 5;366(9497):1653-66. doi: 10.1016/S0140-6736(05)67665-9.