Drug Resistant Epilepsy: Clinical and Genetic Study

Epilepsy, Drug Resistant Clinical Trial

Official title:

Clinical and Genetic Factors Associated With Drug Resistance of Epilepsy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04166305
• Other study ID #: Mansoura University Hospital 6
• Status: Recruiting
• Start date: November 1, 2019
• Est. completion date: November 1, 2020

Study information

• Verified date: November 2019
• Source: Mansoura University Hospital
• Contact: Esmael M Ahmed, MD
• Phone: 00201000372787
• Email: deltaneuro[@]yahoo.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Description:

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. All epileptic patient will be recruited from outpatient epilepsy clinic, Department of Neurology, Mansoura University hospital. The control consists of 60 Age and gender matched healthy individual with negative past and family history of epilepsy and febrile convulsion.

Subjects:

Inclusion criteria:

1. Patient with diagnosis of epilepsy (idiopathic or cryptogenic/symptomatic), according to the International League Against Epilepsy classification confirmed by electroencephalogram.

2. Treatment with at least one AED, long enough to achieve the optimal dose; drug-resistance and drug-responsiveness, according to the criteria ILAE 2010.

3. Written consent obtained from a patient or legal guardian.

Exclusion criteria:

1. Patient with severe adverse anti epileptic drug reactions.

2. Patient with unreliable records of seizure frequency.

3. Patient with poor compliance with AEDs,.

4. Patient with significant psychiatric comor- bidity,

5. Patient with progressive systemic disorders .

6. Patient with history of alcohol or drug abuse.

7. Epileptic patients in clinical remission or with gradual withdrawal of therapy.

8. Epileptic patients with therapy titration phase.

Methods:

After an informed consent, all participants will be subjected to the following;

1. A detailed history taking; including age, sex, age of onset , type of seizure, duration of epilepsy, pretreatment and post treatment seizure frequency , and drugs (antiepileptic drugs, others).

2. Full laboratory investigation including (complete blood count, liver function test, serum creatinine, electrolyte assay, thyroid profile, blood sugar test).

3. Serum level of antiepileptic drug.

4. Electroencephalogram in order to localize site of paroxysmal activity.

5. MRI brain: T1, T2 and FLAIR: axial and coronal cuts to detect any structural abnormalities,

6. Both control and epileptic patient will underwent 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 180
• Est. completion date: November 1, 2020
• Est. primary completion date: October 1, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Years to 16 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Drug Resistant Epilepsy
• Epilepsy
• Epilepsy, Drug Resistant

Intervention

Genetic:
• 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

Locations

Country	Name	City	State
Egypt	Mansoura University Hospital	Mansoura

Sponsors (1)

Lead Sponsor	Collaborator
Mansoura University Hospital

Country where clinical trial is conducted

Egypt, 

References & 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. — View Citation

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

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 — View Citation

Kwan P, Arzimanoglou A, Berg AT, Brodie MJ, Allen Hauser W, Mathern G, Moshé 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. — View Citation

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 — View Citation

Lorigados Pedre L, Morales Chacón LM, Orozco Suárez S, Pavón Fuentes N, Estupiñán Díaz B, Serrano Sánchez T, García Maeso I, Rocha Arrieta L. Inflammatory mediators in epilepsy. Curr Pharm Des. 2013;19(38):6766-72. Review. — View Citation

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, Za — View Citation

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):e1820 — View Citation

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

Sánchez MB, Herranz JL, Leno C, Arteaga R, Oterino A, Valdizán EM, Nicolás JM, Adín 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 — View Citation

Téllez-Zenteno JF, Hernández-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 — View Citation

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. — View Citation

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

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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