Effect of Carbamazepine and Oxcarbazepine on Serum Neuron-specific Enolase and S100B in Focal Seizures

NCT ID: NCT02705768

Last Updated: 2017-09-19

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

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

90 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-04-30

Study Completion Date

2017-03-31

Brief Summary

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The present study has been planned to assess the level of serum neuron-specific enolase (NSE) in focal seizures and its changes after antiepileptic therapy.

Detailed Description

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Epileptic seizures can cause neuronal cell death, enhanced neurogenesis, axonal sprouting, dendritic changes, and reactive gliosis. Histopathological analyses have suggested that the initial insult and recurrent seizures contribute to the neuronal damage. Activation of mesial temporal structures is more likely to cause damage than that of other areas of brain; therefore, one of the consequences of prolonged seizures is selective neuronal loss in the hippocampus. The excitotoxic damage is considered the most important mechanism of injury but there is also evidence that programmed cell death contributes to neuronal damage.

Various biomarkers of brain damage have been studied in the context of epilepsy and brain damage but most widely investigated biochemical biomarker is neuron-specific enolase (NSE). NSE is γγ-isoenzyme of enolase involved in glycolysis pathway. NSE originates predominantly from the cytoplasm of neurons and neuroendocrine cells. Neuronal damage and impairment of blood brain barrier integrity can be detected by the release of NSE into cerebrospinal fluid (CSF) and eventually into blood. NSE is therefore regarded as a marker of neuronal damage and prognosis in various disorders associated with cell damage in the central or peripheral nervous system.

CSF and serum NSE levels obtained within first 48 hours were found to be elevated and correlated well with the duration of epilepsy and outcome of patients. Some studies have shown elevated NSE levels in temporal lobe epilepsy, after single tonic-clonic seizures, and status epilepticus. Literature review reveals that there is lack of data on serum NSE in focal seizures and there is no study on the effect of antiepileptic drugs on the level of serum NSE. So the present study has been planned to assess the level of serum NSE in focal seizures and its changes after antiepileptic therapy.

Conditions

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Seizures, Focal

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Healthy control

Twenty five (25) healthy individuals of same age group will serve as the control group. Control subjects will be evaluated at baseline only.

Group Type NO_INTERVENTION

No interventions assigned to this group

Carbamazepine group

Twenty five (25) patients recruited in this group will receive Tab. Carbamazepine. Carbamazepine will be started with a dose of 200 mg/day for one week and then increased to 400 mg/day for one week and then 600mg/day for next two weeks.

Group Type EXPERIMENTAL

Carbamazepine

Intervention Type DRUG

Carbamazepine will be started with a dose of 200 mg/day for one week and then increased to 400 mg/day for one week and then 600mg/day for next two weeks.

Oxcarbazepine group

Twenty five (25) patients recruited in this group will receive Tab. Oxcarbazepine. Oxcarbazepine will be started with 10mg/kg daily dose for one week followed by 15mg/kg daily for next one week and then will be increased to 20mg/kg for next two weeks.

Group Type EXPERIMENTAL

Oxcarbazepine

Intervention Type DRUG

Oxcarbazepine will be started with 10mg/kg daily dose for one week followed by 15mg/kg daily for next one week and then will be increased to 20mg/kg for next two weeks.

Interventions

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Carbamazepine

Carbamazepine will be started with a dose of 200 mg/day for one week and then increased to 400 mg/day for one week and then 600mg/day for next two weeks.

Intervention Type DRUG

Oxcarbazepine

Oxcarbazepine will be started with 10mg/kg daily dose for one week followed by 15mg/kg daily for next one week and then will be increased to 20mg/kg for next two weeks.

Intervention Type DRUG

Other Intervention Names

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Tegretol Oxetol

Eligibility Criteria

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Inclusion Criteria

* All patients with the clinical diagnosis of localization related epilepsy/focal seizure (International League Against Epilepsy 2010) with a history of an episode of seizure within 48 hours of presentation
* Treatment naïve patients or patients who had not taken any treatment for at least 3 weeks before inclusion.

Exclusion Criteria

* History of any recent traumatic brain injury, cerebral ischemia/transient ischemic attack/stroke
* Patients with neuroendocrinal tumours
* History of any invasive neurosurgical /non-invasive neuropsychiatric procedure.
* Patients who are already under treatment for the presenting conditions.
* Medication history of psychoactive or central nervous system depressant drugs
* Pregnant and nursing women
Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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All India Institute of Medical Sciences, Bhubaneswar

OTHER

Sponsor Role lead

Responsible Party

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RITUPARNA MAITI

Associate Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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DEBASISH HOTA, DM

Role: STUDY_DIRECTOR

AIIMS, Bhubaneswar

Locations

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AIIMS, Bhubaneswar

Bhubaneswar, Odisha, India

Site Status

Countries

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India

References

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Sutula TP. Mechanisms of epilepsy progression: current theories and perspectives from neuroplasticity in adulthood and development. Epilepsy Res. 2004 Jul-Aug;60(2-3):161-71. doi: 10.1016/j.eplepsyres.2004.07.001.

Reference Type RESULT
PMID: 15380560 (View on PubMed)

Holmes GL. Seizure-induced neuronal injury: animal data. Neurology. 2002 Nov 12;59(9 Suppl 5):S3-6. doi: 10.1212/wnl.59.9_suppl_5.s3.

Reference Type RESULT
PMID: 12428025 (View on PubMed)

Henshall DC, Clark RS, Adelson PD, Chen M, Watkins SC, Simon RP. Alterations in bcl-2 and caspase gene family protein expression in human temporal lobe epilepsy. Neurology. 2000 Jul 25;55(2):250-7. doi: 10.1212/wnl.55.2.250.

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Kato K, Ishiguro Y, Suzuki F, Ito A, Semba R. Distribution of nervous system-specific forms of enolase in peripheral tissues. Brain Res. 1982 Apr 15;237(2):441-8. doi: 10.1016/0006-8993(82)90455-3.

Reference Type RESULT
PMID: 7044473 (View on PubMed)

Royds JA, Davies-Jones GA, Lewtas NA, Timperley WR, Taylor CB. Enolase isoenzymes in the cerebrospinal fluid of patients with diseases of the nervous system. J Neurol Neurosurg Psychiatry. 1983 Nov;46(11):1031-6. doi: 10.1136/jnnp.46.11.1031.

Reference Type RESULT
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DeGiorgio CM, Correale JD, Gott PS, Ginsburg DL, Bracht KA, Smith T, Boutros R, Loskota WJ, Rabinowicz AL. Serum neuron-specific enolase in human status epilepticus. Neurology. 1995 Jun;45(6):1134-7. doi: 10.1212/wnl.45.6.1134.

Reference Type RESULT
PMID: 7783877 (View on PubMed)

Correale J, Rabinowicz AL, Heck CN, Smith TD, Loskota WJ, DeGiorgio CM. Status epilepticus increases CSF levels of neuron-specific enolase and alters the blood-brain barrier. Neurology. 1998 May;50(5):1388-91. doi: 10.1212/wnl.50.5.1388.

Reference Type RESULT
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Palmio J, Keranen T, Alapirtti T, Hulkkonen J, Makinen R, Holm P, Suhonen J, Peltola J. Elevated serum neuron-specific enolase in patients with temporal lobe epilepsy: a video-EEG study. Epilepsy Res. 2008 Oct;81(2-3):155-60. doi: 10.1016/j.eplepsyres.2008.05.006. Epub 2008 Jul 1.

Reference Type RESULT
PMID: 18595663 (View on PubMed)

Chang CC, Lui CC, Lee CC, Chen SD, Chang WN, Lu CH, Chen NC, Chang AY, Chan SH, Chuang YC. Clinical significance of serological biomarkers and neuropsychological performances in patients with temporal lobe epilepsy. BMC Neurol. 2012 Mar 14;12:15. doi: 10.1186/1471-2377-12-15.

Reference Type RESULT
PMID: 22417223 (View on PubMed)

Buttner T, Lack B, Jager M, Wunsche W, Kuhn W, Muller T, Przuntek H, Postert T. Serum levels of neuron-specific enolase and s-100 protein after single tonic-clonic seizures. J Neurol. 1999 Jun;246(6):459-61. doi: 10.1007/s004150050383.

Reference Type RESULT
PMID: 10431771 (View on PubMed)

Rabinowicz AL, Correale J, Boutros RB, Couldwell WT, Henderson CW, DeGiorgio CM. Neuron-specific enolase is increased after single seizures during inpatient video/EEG monitoring. Epilepsia. 1996 Feb;37(2):122-5. doi: 10.1111/j.1528-1157.1996.tb00002.x.

Reference Type RESULT
PMID: 8635421 (View on PubMed)

Duncan JS, Sander JW. The Chalfont Seizure Severity Scale. J Neurol Neurosurg Psychiatry. 1991 Oct;54(10):873-6. doi: 10.1136/jnnp.54.10.873.

Reference Type RESULT
PMID: 1744641 (View on PubMed)

Cramer JA, French J. Quantitative assessment of seizure severity for clinical trials: a review of approaches to seizure components. Epilepsia. 2001 Jan;42(1):119-29. doi: 10.1046/j.1528-1157.2001.19400.x.

Reference Type RESULT
PMID: 11207795 (View on PubMed)

Cramer JA, Perrine K, Devinsky O, Bryant-Comstock L, Meador K, Hermann B. Development and cross-cultural translations of a 31-item quality of life in epilepsy inventory. Epilepsia. 1998 Jan;39(1):81-8. doi: 10.1111/j.1528-1157.1998.tb01278.x.

Reference Type RESULT
PMID: 9578017 (View on PubMed)

Maiti R, Mishra BR, Sanyal S, Mohapatra D, Parida S, Mishra A. Effect of carbamazepine and oxcarbazepine on serum neuron-specific enolase in focal seizures: A randomized controlled trial. Epilepsy Res. 2017 Dec;138:5-10. doi: 10.1016/j.eplepsyres.2017.10.003. Epub 2017 Oct 6.

Reference Type DERIVED
PMID: 29028517 (View on PubMed)

Other Identifiers

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T/IM -NF/Pharm/15/30

Identifier Type: -

Identifier Source: org_study_id