Efficacy Study of Folic Acid Supplementation in Adolescent Epileptics

NCT ID: NCT02318446

Last Updated: 2014-12-17

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

Clinical Phase

PHASE3

Total Enrollment

36 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-03-31

Study Completion Date

2016-05-31

Brief Summary

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The present study is planned to study effect of folic acid supplementation on homocysteine levels and CV risk factors such as BP and lipids in adolescent epileptics taking anti-epileptic drugs (AEDs).

Detailed Description

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Scientific background, significance and impact value of the project:

Homocysteine is a thiol-containing amino acid formed as an intermediate product during the methionine metabolism. Re-methylation pathway recycles Homocysteine back to methionine and requires vitamin B12 and folic acid as cofactors. \[1\] The concentration of circulating total homocysteine is a sensitive marker of inadequate folate and vitamin B12 status. Elevated homocysteine concentrations are associated with an increased risk for cardiovascular (CV) disease. \[2\] The total homocysteine level is the lowest in children and an increase with age is higher in male sex. \[2\] The cutoffs for homocysteine level in adolescent range from 4.3 to 9.9 µmol/l, and hyperhomocysteinemia is defined as homocysteine \>10.9 µmol/l. \[3\] Lower folate and higher homocysteine concentrations may put adolescent on AEDs at special risk for atherosclerosis in their adulthood. \[4\] This demands early intervention as Asian Indian adolescents are genetically more exposed to cadiovascular disease(CVD) risks, AED therapy is an additional risk for developing future CVDs. Adolescent epileptics on AED have to take it for long time, and homocysteine elevation itself has got epileptogenic potential and can cause the risk developing refractory epilepsy. \[5\] Literature search reveals several studies depicting role of vitamin B12 in regulation of blood homocysteine levels. \[6, 7\] However, the studies confirming role of folic acid supplementation in hyperhomocysteinemia and related CV diseases are fewer and scarce in AEDs induced hyperhomocysteinemia. Few studies have reported negative correlation between hyperhomocysteinemia and low folic acid levels in patients on AEDs. \[8\] At the same time few studies have reported effectiveness of folic acid supplementation to normalize the homocysteine levels. \[9\] Considering the results of various studies many doctors are now prescribing folic acid along with AEDs, although there is a scarcity of data from India. In this context, the present study is planned to study effect of folic acid supplementation on homocysteine levels and CV risk factors such as BP and lipids in adolescent epileptics taking AEDs.

Conditions

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Epilepsy

Keywords

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Anti-epileptic drugs Folic acid Homocysteine

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Control group

Will receive Oral saccharine tablet daily for 1month along with their existing antiepileptic therapy

Group Type PLACEBO_COMPARATOR

Saccharine

Intervention Type DRUG

Placebo group(n=12) Existing Anti-epileptic Drugs + Oral saccharine 10 mg tablet daily for 1month

Test group

Will receive Oral Folic acid 1mg tablet daily for 1month along with their existing antiepileptic therapy

Group Type EXPERIMENTAL

Folic Acid

Intervention Type DRUG

Test group(n= 24) Existing Anti-epileptic Drugs + Oral Folic acid 1mg tablet daily for 1month

Interventions

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Folic Acid

Test group(n= 24) Existing Anti-epileptic Drugs + Oral Folic acid 1mg tablet daily for 1month

Intervention Type DRUG

Saccharine

Placebo group(n=12) Existing Anti-epileptic Drugs + Oral saccharine 10 mg tablet daily for 1month

Intervention Type DRUG

Other Intervention Names

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Folvite Sugar free

Eligibility Criteria

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Inclusion Criteria

* Diagnosed epileptic patients of either sex with age between 10-19 yrs (\<19yrs), coming to the medicine Out Patient /In Patient Departments and undergoing AED therapy for more than 6 months.
* Epileptics with high homocysteine levels i.e. \> 10.9 µmol/L (Normal homocysteine levels are 4.3-9.9 µmol/L for male and 3.3-7.2 µmol/L for female adolescent and a high homocysteine concentration is deaned as at least 11.4 µmol/L for male and at least 10.4 µmol/L for female. Gender mean of high homocysteine concentration is 10.9 µmol/L) \[5\]

Exclusion Criteria

* Pregnancy and lactation
* Patients with diabetes, Ischemic heart disease (IHD), stroke, malignancy and psychiatric diseases are excluded from study.
* The patients receiving vitamin supplements or who had clinical evidence for an acute illness, renal dysfunction, thyroid dysfunction, chronic inflammatory diseases, inborn errors of homocysteine, cobalamin or folate metabolism, or any other condition known to interfere with homocysteine metabolism will be excluded
* Patients who are already involved in any other trial.
* Patients not willing to fill consent/ assent form are also excluded from study.
Minimum Eligible Age

10 Years

Maximum Eligible Age

19 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Maharashtra University of Health Sciences

OTHER

Sponsor Role lead

Responsible Party

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Uma Bhosale

Professor in Department of Pharmacology, SKNMC & GH, Pune-41

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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UMA A. BHOSALE, MD

Role: PRINCIPAL_INVESTIGATOR

Smt. Kashibai Navale Medical College and General Hospital

Locations

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Smt. Kashibai Navale Medical College and General Hospital

Pune, Maharashtra, India

Site Status

Countries

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India

Central Contacts

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UMA A. BHOSALE, MD

Role: CONTACT

Phone: 02024106

Email: [email protected]

Facility Contacts

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Uma A. Bhosale, MD

Role: primary

References

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Hoffer LJ. Homocysteine remethylation and trans-sulfuration. Metabolism. 2004 Nov;53(11):1480-3. doi: 10.1016/j.metabol.2004.06.003.

Reference Type BACKGROUND
PMID: 15536605 (View on PubMed)

Selhub J, Miller JW. The pathogenesis of homocysteinemia: interruption of the coordinate regulation by S-adenosylmethionine of the remethylation and transsulfuration of homocysteine. Am J Clin Nutr. 1992 Jan;55(1):131-8. doi: 10.1093/ajcn/55.1.131.

Reference Type BACKGROUND
PMID: 1728812 (View on PubMed)

Selhub J, Jacques PF, Rosenberg IH, Rogers G, Bowman BA, Gunter EW, Wright JD, Johnson CL. Serum total homocysteine concentrations in the third National Health and Nutrition Examination Survey (1991-1994): population reference ranges and contribution of vitamin status to high serum concentrations. Ann Intern Med. 1999 Sep 7;131(5):331-9. doi: 10.7326/0003-4819-131-5-199909070-00003.

Reference Type BACKGROUND
PMID: 10475885 (View on PubMed)

Osganian SK, Stampfer MJ, Spiegelman D, Rimm E, Cutler JA, Feldman HA, Montgomery DH, Webber LS, Lytle LA, Bausserman L, Nader PR. Distribution of and factors associated with serum homocysteine levels in children: Child and Adolescent Trial for Cardiovascular Health. JAMA. 1999 Apr 7;281(13):1189-96. doi: 10.1001/jama.281.13.1189.

Reference Type BACKGROUND
PMID: 10199428 (View on PubMed)

Cheng LS, Prasad AN, Rieder MJ. Relationship between antiepileptic drugs and biological markers affecting long-term cardiovascular function in children and adolescents. Can J Clin Pharmacol. 2010 Winter;17(1):e5-46. Epub 2010 Jan 4.

Reference Type BACKGROUND
PMID: 20051609 (View on PubMed)

Sato Y, Ouchi K, Funase Y, Yamauchi K, Aizawa T. Relationship between metformin use, vitamin B12 deficiency, hyperhomocysteinemia and vascular complications in patients with type 2 diabetes. Endocr J. 2013;60(12):1275-80. doi: 10.1507/endocrj.ej13-0332. Epub 2013 Sep 8.

Reference Type BACKGROUND
PMID: 24018893 (View on PubMed)

Satyanarayana A, Balakrishna N, Pitla S, Reddy PY, Mudili S, Lopamudra P, Suryanarayana P, Viswanath K, Ayyagari R, Reddy GB. Status of B-vitamins and homocysteine in diabetic retinopathy: association with vitamin-B12 deficiency and hyperhomocysteinemia. PLoS One. 2011;6(11):e26747. doi: 10.1371/journal.pone.0026747. Epub 2011 Nov 1.

Reference Type BACKGROUND
PMID: 22069468 (View on PubMed)

Coppola G, Ingrosso D, Operto FF, Signoriello G, Lattanzio F, Barone E, Matera S, Verrotti A. Role of folic acid depletion on homocysteine serum level in children and adolescents with epilepsy and different MTHFR C677T genotypes. Seizure. 2012 Jun;21(5):340-3. doi: 10.1016/j.seizure.2012.02.011. Epub 2012 Mar 16.

Reference Type BACKGROUND
PMID: 22425007 (View on PubMed)

Linnebank M, Moskau S, Semmler A, Widman G, Stoffel-Wagner B, Weller M, Elger CE. Antiepileptic drugs interact with folate and vitamin B12 serum levels. Ann Neurol. 2011 Feb;69(2):352-9. doi: 10.1002/ana.22229. Epub 2011 Jan 19.

Reference Type BACKGROUND
PMID: 21246600 (View on PubMed)

De Lourdes Levy M, Larcher V, Kurz R; Ethics Working Group of the Confederation of European Specialists in Paediatrics (CESP). Informed consent/assent in children. Statement of the Ethics Working Group of the Confederation of European Specialists in Paediatrics (CESP). Eur J Pediatr. 2003 Sep;162(9):629-33. doi: 10.1007/s00431-003-1193-z. Epub 2003 Jul 19.

Reference Type BACKGROUND
PMID: 12884032 (View on PubMed)

Age limits and adolescents. Paediatr Child Health. 2003 Nov;8(9):577-8. doi: 10.1093/pch/8.9.577. No abstract available.

Reference Type BACKGROUND
PMID: 20019831 (View on PubMed)

Related Links

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http://www.who.int/topics/adolescent_health/en/

World Health Organization. \[Accessed May 15, 2014\]; Health topics. Adolescent health. 2011

Other Identifiers

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LTRG/E-1/03/ 1210

Identifier Type: -

Identifier Source: org_study_id