Drug Resistant Epilepsy: Clinical and Genetic Study

NCT04166305 | Unknown

• 1 other identifier: Mansoura University Hospital 6
• Study Type: observational
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

This study is to identify the clinical criteria of drug resistant epilepsy and to explore whether SCN1A c.3184 A/G (rs2298771) and ccl2(rs1024611) polymorphisms could serve as genetic based biomarkers to predict drug resistance among epileptic patient.

Conditions

Epilepsy, Drug Resistant

Keywords

Epilepsy, genetic and drug resistant

Outcome Measures

Primary Outcomes (1)

• Genetic study for SCN1A c.3184 A/G and CCL2-2518G>A polymorphism:

  • DNA analysis: Genomic DNA will be extracted from EDTA-anticoagulated peripheral blood (QIAamp DNA Blood mini kit,QIAGEN). • Genotyping of SCN1A c.3184 A/G(rs2298771) polymorphism

  5-7 days

Study Arms (3)

Drug responders

60 patients are drug responders

Genetic: Genetic study for SCN1A c.3184 A/G and CCL2-2518G>A polymorphism:

Drug resistant

60 patients are drug resistant

Genetic: Genetic study for SCN1A c.3184 A/G and CCL2-2518G>A polymorphism:

The control

The control consists of 60 Age and gender matched healthy individual with negative past and family history of epilepsy and febrile convulsion.

Genetic: Genetic study for SCN1A c.3184 A/G and CCL2-2518G>A polymorphism:

Interventions

Genetic study for SCN1A c.3184 A/G and CCL2-2518G>A polymorphism: GENETIC

DNA analysis: Genomic DNA will be extracted from EDTA-anticoagulated peripheral blood (QIAamp DNA Blood mini kit,QIAGEN). Genotyping of SCN1A c.3184 A/G(rs2298771) polymorphism

Drug resistant; Drug responders; The control

Eligibility Criteria

• Age: 6 Years - 16 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• Sampling Method: Probability Sample

Study Population

This retrospective case control study will be conducted on 120 epileptic patients treated with AEDs, 60 patients are drug responders and 60 patients are drug resistant. The control consists of 60 Age and gender matched healthy individual with negative past and family history of epilepsy and febrile convulsion.

You may qualify if:

• Patient with diagnosis of epilepsy (idiopathic or cryptogenic/symptomatic), according to the International League Against Epilepsy classification confirmed by electroencephalogram.
• Treatment with at least one AED, long enough to achieve the optimal dose; drug-resistance and drug-responsiveness, according to the criteria ILAE 2010.

You may not qualify if:

• Patient with severe adverse anti-epileptic drug reactions.
• Patient with unreliable records of seizure frequency.
• Patient with poor compliance with AEDs,.
• Patient with significant psychiatric comorbidity,
• Patient with progressive systemic disorders .
• Patient with history of alcohol or drug abuse.
• Epileptic patients in clinical remission or with gradual withdrawal of therapy.
• Epileptic patients with therapy titration phase.

Sponsors & Collaborators

• Mansoura University Hospital: lead

Study Sites (1)

Mansoura University Hospital

Al Mansurah, Egypt

RECRUITING

Related Publications (13)

• He X, Li Y, Liu Z, Yue X, Zhao P, Hu J, Wu G, Mao B, Sun D, Zhang H, Song X, Wang Y, Shao J. The association between CCL2 polymorphisms and drug-resistant epilepsy in Chinese children. Epileptic Disord. 2013 Sep;15(3):272-7. doi: 10.1684/epd.2013.0603.

  PMID: 23996681 RESULT

• Kumari R, Lakhan R, Garg RK, Kalita J, Misra UK, Mittal B. Pharmacogenomic association study on the role of drug metabolizing, drug transporters and drug target gene polymorphisms in drug-resistant epilepsy in a north Indian population. Indian J Hum Genet. 2011 May;17 Suppl 1(Suppl 1):S32-40. doi: 10.4103/0971-6866.80357.

  PMID: 21747585 RESULT

• Kasperaviciute D, Sisodiya SM. Epilepsy pharmacogenetics. Pharmacogenomics. 2009 May;10(5):817-36. doi: 10.2217/pgs.09.34.

  PMID: 19450130 RESULT

• 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.

  PMID: 19889013 RESULT

• Lakhan R, Kumari R, Misra UK, Kalita J, Pradhan S, Mittal B. Differential role of sodium channels SCN1A and SCN2A gene polymorphisms with epilepsy and multiple drug resistance in the north Indian population. Br J Clin Pharmacol. 2009 Aug;68(2):214-20. doi: 10.1111/j.1365-2125.2009.03437.x.

  PMID: 19694741 RESULT

• Lorigados Pedre L, Morales Chacon LM, Orozco Suarez S, Pavon Fuentes N, Estupinan Diaz B, Serrano Sanchez T, Garcia Maeso I, Rocha Arrieta L. Inflammatory mediators in epilepsy. Curr Pharm Des. 2013;19(38):6766-72. doi: 10.2174/1381612811319380009.

  PMID: 23530510 RESULT

• Manna I, Gambardella A, Bianchi A, Striano P, Tozzi R, Aguglia U, Beccaria F, Benna P, Campostrini R, Canevini MP, Condino F, Durisotti C, Elia M, Giallonardo AT, Iudice A, Labate A, La Neve A, Michelucci R, Muscas GC, Paravidino R, Zaccara G, Zucca C, Zara F, Perucca E. A functional polymorphism in the SCN1A gene does not influence antiepileptic drug responsiveness in Italian patients with focal epilepsy. Epilepsia. 2011 May;52(5):e40-4. doi: 10.1111/j.1528-1167.2011.03097.x.

  PMID: 21561445 RESULT

• Marchi N, Granata T, Freri E, Ciusani E, Ragona F, Puvenna V, Teng Q, Alexopolous A, Janigro D. Efficacy of anti-inflammatory therapy in a model of acute seizures and in a population of pediatric drug resistant epileptics. PLoS One. 2011 Mar 28;6(3):e18200. doi: 10.1371/journal.pone.0018200.

  PMID: 21464890 RESULT

• Pohlmann-Eden B, Weaver DF. The puzzle(s) of pharmacoresistant epilepsy. Epilepsia. 2013 May;54 Suppl 2:1-4. doi: 10.1111/epi.12174.

  PMID: 23646961 RESULT

• Sanchez MB, Herranz JL, Leno C, Arteaga R, Oterino A, Valdizan EM, Nicolas JM, Adin J, Armijo JA. Genetic factors associated with drug-resistance of epilepsy: relevance of stratification by patient age and aetiology of epilepsy. Seizure. 2010 Mar;19(2):93-101. doi: 10.1016/j.seizure.2009.12.004. Epub 2010 Jan 12.

  PMID: 20064729 RESULT

• Tellez-Zenteno JF, Hernandez-Ronquillo L, Buckley S, Zahagun R, Rizvi S. A validation of the new definition of drug-resistant epilepsy by the International League Against Epilepsy. Epilepsia. 2014 Jun;55(6):829-34. doi: 10.1111/epi.12633. Epub 2014 May 14.

  PMID: 24828683 RESULT

• Wirrell EC. Predicting pharmacoresistance in pediatric epilepsy. Epilepsia. 2013 May;54 Suppl 2:19-22. doi: 10.1111/epi.12179.

  PMID: 23646966 RESULT

• Walker L, Sills GJ. Inflammation and epilepsy: the foundations for a new therapeutic approach in epilepsy? Epilepsy Curr. 2012 Jan;12(1):8-12. doi: 10.5698/1535-7511-12.1.8.

  PMID: 22368518 RESULT

MeSH Terms

Conditions

Drug Resistant Epilepsy; Epilepsy

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Esmael M Ahmed, MD

  Assistant Prof of Neurology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Esmael M Ahmed, MD

CONTACT

00201000372787; deltaneuro@yahoo.com

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Prof of Neurology

Study Record Dates

• First Submitted: November 14, 2019
• First Posted: November 18, 2019
• Study Start: November 1, 2019
• Primary Completion: October 1, 2020
• Study Completion: November 1, 2020
• Last Updated: November 18, 2019

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)