Drug Resistant Epilepsy: Clinical and Genetic Study

NCT ID: NCT04166305

Last Updated: 2019-11-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

180 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-11-01

Study Completion Date

2020-11-01

Brief Summary

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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.

Detailed Description

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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).

Conditions

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Epilepsy, Drug Resistant

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

RETROSPECTIVE

Study Groups

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Drug responders

60 patients are drug responders

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

Intervention Type 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

60 patients are drug resistant

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

Intervention Type 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

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

Intervention Type 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

Interventions

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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

Intervention Type GENETIC

Eligibility Criteria

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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.
Minimum Eligible Age

6 Years

Maximum Eligible Age

16 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Mansoura University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Ahmed Esmael

Assistant Prof of Neurology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Esmael M Ahmed, MD

Role: PRINCIPAL_INVESTIGATOR

Assistant Prof of Neurology

Locations

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Mansoura University Hospital

Al Mansurah, , Egypt

Site Status RECRUITING

Countries

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Egypt

Central Contacts

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Esmael M Ahmed, MD

Role: CONTACT

00201000372787

Facility Contacts

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Esmael M Ahmed, MD

Role: primary

00201000382898

References

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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.

Reference Type RESULT
PMID: 23996681 (View on PubMed)

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.

Reference Type RESULT
PMID: 21747585 (View on PubMed)

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

Reference Type RESULT
PMID: 19450130 (View on PubMed)

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.

Reference Type RESULT
PMID: 19889013 (View on PubMed)

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.

Reference Type RESULT
PMID: 19694741 (View on PubMed)

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.

Reference Type RESULT
PMID: 23530510 (View on PubMed)

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.

Reference Type RESULT
PMID: 21561445 (View on PubMed)

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.

Reference Type RESULT
PMID: 21464890 (View on PubMed)

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

Reference Type RESULT
PMID: 23646961 (View on PubMed)

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.

Reference Type RESULT
PMID: 20064729 (View on PubMed)

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.

Reference Type RESULT
PMID: 24828683 (View on PubMed)

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

Reference Type RESULT
PMID: 23646966 (View on PubMed)

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.

Reference Type RESULT
PMID: 22368518 (View on PubMed)

Other Identifiers

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Mansoura University Hospital 6

Identifier Type: -

Identifier Source: org_study_id

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