Helicobacter Pylori Eradication Therapy for Epileptic Children

Helicobacter Pylori Infection Clinical Trial

Official title:

Effect of Treating Helicobacter Pylori Infection on Seizure Frequency in Children With Drug-Resistant Idiopathic Generalized Epilepsy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05297695
• Other study ID #: soh-med-22-03-13
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: April 20, 2022
• Est. completion date: December 30, 2023

Study information

• Verified date: January 2024
• Source: Sohag University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Helicobacter pylori (H. pylori) infection is associated with several health problems. The role of H. pylori infection in epilepsy has been investigated in a few studies. To the best of our knowledge, there have been no previous studies on the effect of treating H. pylori infection on seizure frequency among children with drug-resistant idiopathic generalized epilepsy. This study aims to evaluate the effect of treating H. pylori infection on seizure frequency among children with drug-resistant idiopathic generalized epilepsy.

Description:

Helicobacter pylori (H. pylori) is a spiral-shaped Gram-negative bacterium, which causes chronic infection in more than 50% of human population. H. pylori infection is associated with several gastrointestinal disorders, such as gastritis and gastric/duodenal ulcers. Moreover, accumulating body of evidence indicates the possible role of H. Pylori infection in extraintestinal health problems, such as iron deficiency anemia, immune thrombocytopenic purpura (ITP), numerous dermatological diseases, Alzheimer disease, Parkinson's disease, multiple sclerosis, and epilepsy. Epilepsy is a common neurological disorder characterized by recurrent unprovoked seizures. This condition affects 0.5% to 1% of all children and is associated with neurobiological, cognitive, psychological, and social consequences. Seizures can usually be controlled by anti-epileptic drugs (AEDs) in up to two-thirds of children with epilepsy. However, this leaves a significant part of epileptic children whose seizures are not controlled by pharmacotherapy. The development of epilepsy is highly complex and can be attributed to multiple etiologies classified into structural (e.g., malformation, trauma, ischemia), genetic, infectious, metabolic, and immune factors. However, the etiology remains unknown in about half of epileptic children. Idiopathic generalized epilepsies (IGE) constitute about one-third of all epilepsies. Efforts to explore new possible mechanisms contributing to the development of epilepsy, particularly drug-resistant IGE, could contribute to the development of new therapeutic strategies to improve patients' outcomes. The role of H. pylori infection in epilepsy has been investigated in a few studies, some of which reported that the seroprevalence of H. pylori infection is significantly higher in patients with idiopathic epilepsy compared with patients with other chronic diseases, and that H. pylori infection is associated with poor prognosis. Potential H. pylori-induced epileptic effects are probably immune-mediated that can be attributed to a cross-mimicry mechanism between H. pylori and human cellular phospholipids with production of autoimmune antibodies (e.g., anti-cardiolipin) and H. pylori infection-related activation of pro-inflammatory cells with systemic release of proinflammatory cytokines (e.g., IL-6, 8 and TNF- α) which are involved in disruption of the blood-brain barrier and neuroinflammation. To the best of our knowledge, there have been no previous studies on the effect of treating H. pylori infection on seizure frequency among children with drug-resistant IGE. This study aims to evaluate the effect of treating H. pylori infection on seizure frequency among children with drug-resistant IGE.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 126
• Est. completion date: December 30, 2023
• Est. primary completion date: October 10, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years to 18 Years

Eligibility

Inclusion Criteria:

• Age between 4 and 18 years.
• Idiopathic generalized epilepsies (IGE), including childhood absence epilepsy, juvenile absence epilepsy, juvenile myoclonic epilepsy, or IGE with generalized tonic-clonic seizures only (IGE-TCS).
• Drug-resistant epilepsy, defined as failure of adequate trials of two tolerated and appropriately chosen and used anti-epileptic drugs schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom
• Positive H. pylori stool antigen (HpSA) test (at initial screening).

Exclusion Criteria:

• Failure to obtain informed consent.
• Presence of a medical indication for treating H. pylori infection, including gastric or duodenal ulcer, chronic immune thrombocytopenic purpura, and refractory iron deficiency anemia.
• Known allergy or contraindications to any of the study drugs.
• Treatment with antibiotics and/or proton pump inhibitors in the last 2 months.

Related Conditions & MeSH terms

• Epilepsy
• Epilepsy, Generalized
• Helicobacter Infections
• Helicobacter Pylori Infection
• Infections

Intervention

Drug:
• Triple therapy for H. pylori infection
Triple therapy for H. pylori infection (Esomeprazole, Amoxicillin, and Clarithromycin) for two weeks

Locations

Country	Name	City	State
Egypt	Sohag University Hospital	Sohag

Sponsors (1)

Lead Sponsor	Collaborator
Sohag University

Country where clinical trial is conducted

Egypt, 

References & Publications (8)

Fine A, Wirrell EC. Seizures in Children. Pediatr Rev. 2020 Jul;41(7):321-347. doi: 10.1542/pir.2019-0134. — View Citation

Fisher RS, Acevedo C, Arzimanoglou A, Bogacz A, Cross JH, Elger CE, Engel J Jr, Forsgren L, French JA, Glynn M, Hesdorffer DC, Lee BI, Mathern GW, Moshe SL, Perucca E, Scheffer IE, Tomson T, Watanabe M, Wiebe S. ILAE official report: a practical clinical definition of epilepsy. Epilepsia. 2014 Apr;55(4):475-82. doi: 10.1111/epi.12550. Epub 2014 Apr 14. — View Citation

Korotkaya Y, Shores D. Helicobacter pylori in Pediatric Patients. Pediatr Rev. 2020 Nov;41(11):585-592. doi: 10.1542/pir.2019-0048. — View Citation

Kwan P, Arzimanoglou A, Berg AT, Brodie MJ, Allen Hauser W, Mathern G, Moshe SL, Perucca E, Wiebe S, French J. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia. 2010 Jun;51(6):1069-77. doi: 10.1111/j.1528-1167.2009.02397.x. Epub 2009 Nov 3. Erratum In: Epilepsia. 2010 Sep;51(9):1922. — View Citation

Okuda M, Miyashiro E, Nakazawa T, Minami K, Koike M. Helicobacter pylori infection and idiopathic epilepsy. Am J Med. 2004 Feb 1;116(3):209-10. doi: 10.1016/j.amjmed.2003.05.005. No abstract available. — View Citation

Ozturk A, Ozturk CE, Ozdemirli B, Yucel M, Bahcebasi T. Helicobacter pylori infection in epileptic patients. Seizure. 2007 Mar;16(2):147-52. doi: 10.1016/j.seizure.2006.10.015. Epub 2006 Nov 27. — View Citation

Scheffer IE, Berkovic S, Capovilla G, Connolly MB, French J, Guilhoto L, Hirsch E, Jain S, Mathern GW, Moshe SL, Nordli DR, Perucca E, Tomson T, Wiebe S, Zhang YH, Zuberi SM. ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017 Apr;58(4):512-521. doi: 10.1111/epi.13709. Epub 2017 Mar 8. — View Citation

Yao G, Wang P, Luo XD, Yu TM, Harris RA, Zhang XM. Meta-analysis of association between Helicobacter pylori infection and multiple sclerosis. Neurosci Lett. 2016 May 4;620:1-7. doi: 10.1016/j.neulet.2016.03.037. Epub 2016 Mar 23. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Seizure improvement	= 50% seizure frequency reduction compared with baseline	2.5 months following H. pylori eradication therapy
Secondary	Need for escalation of antiepileptic drugs	Need for escalation of antiepileptic drugs compared with baseline	2.5 months following H. pylori eradication therapy
Secondary	Occurrence of status epilepticus		2.5 months following H. pylori eradication therapy
Secondary	Occurrence of adverse effects of H. pylori eradication therapy		2.5 months following H. pylori eradication therapy