Clinical trial NCT05297695: Helicobacter Pylori Eradication Therapy for Epileptic Children
Official title: Effect of Treating Helicobacter Pylori Infection on Seizure Frequency in Children With Drug-Resistant Idiopathic Generalized Epilepsy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Epilepsy, Generalized
Helicobacter Pylori Infection
Keywords: Children
Epilepsy
Helicobacter pylori
Treatment
Seizure
Lead sponsor: Sohag University
Sponsor class: OTHER
First posted: 2022-03-28
Enrollment: 126
Sex: ALL
Minimum age (years): 4
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Seizure improvement
timeFrame: 2.5 months following H. pylori eradication therapy
Secondary outcomes:
measure: Need for escalation of antiepileptic drugs
timeFrame: 2.5 months following H. pylori eradication therapy
measure: Occurrence of status epilepticus
timeFrame: 2.5 months following H. pylori eradication therapy
measure: Occurrence of adverse effects of H. pylori eradication therapy
timeFrame: 2.5 months following H. pylori eradication therapy
Other outcomes:
Locations:
city: Sohag
country: Egypt
facility: Sohag University Hospital
Study officials:
affiliation: Sohag University
name: Montaser M Mohamed, MD, PhD
role: STUDY_CHAIR
References:
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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.