EpilepsyPhase 3NCT02318446
Efficacy Study of Folic Acid Supplementation in Adolescent Epileptics
A Phase 3 study testing Folic Acid and Saccharine in people with Epilepsy, run by Maharashtra University of Health Sciences at 1 site in India.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 10 to 19 years
- Conditions the study is for
- Epilepsy
- What is being tested?
- Folic Acid and Saccharine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 1 siteIndia
- Study dates
- Mar 2015to May 2016
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 10 to 19 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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]
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
India1 site
Smt. Kashibai Navale Medical College and General Hospital
Pune, Maharashtra, 411041
Uma A. Bhosale, MD, 02024106 ext. 148, umabhosale2000@gmail.com
About this study
Official title: Efficacy Study of Folic Acid Supplementation on Homocysteine Levels in Adolescent Epileptics Taking Antiepileptic Drugs: A Single Blind Randomized Controlled Clinical Trial
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).
Read the detailed description
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
- Epilepsy
- Being tested
- Folic Acid, Saccharine
- Keywords
- Anti-epileptic drugs, Folic acid, Homocysteine
- Medical subject headings
- Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Folic AcidDrug
Also called Folvite
Test group(n= 24) Existing Anti-epileptic Drugs + Oral Folic acid 1mg tablet daily for 1month
SaccharineDrug
Also called Sugar free
Placebo group(n=12) Existing Anti-epileptic Drugs + Oral saccharine 10 mg tablet daily for 1month
| Study group | Role | What they receive |
|---|---|---|
| Control group | Placebo comparator | Will receive Oral saccharine tablet daily for 1month along with their existing antiepileptic therapy Receives: Drug: Saccharine |
| Test group | Experimental | Will receive Oral Folic acid 1mg tablet daily for 1month along with their existing antiepileptic therapy Receives: Drug: Folic Acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Decrease in serum homocysteine levels by 2 µmol/l
Measured: 1 month
Secondary outcomes (2)
Change in baseline serum lipids
Change in baseline serum lipids following Anti-epileptic therapy will be compared between placebo and test group.
Measured: 1 month
Change in baseline systolic blood pressure
Change in baseline systolic blood pressure will be compared between placebo and test group.
Measured: 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2014 (estimated)
- Study startMar 2015
- Primary completionApr 2016 (estimated)
- Study completionMay 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for EpilepsyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Maharashtra University of Health Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Uma Bhosale, Maharashtra University of Health Sciences
- Investigators
- UMA A. BHOSALE, MD, Principal investigator, Smt. Kashibai Navale Medical College and General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02318446
- Sponsor's protocol ID
- LTRG/E-1/03/ 1210
- Status last verified
- Dec 2014
- First submitted
- 10 Dec 2014
- Last updated
- 17 Dec 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Hoffer LJ. Homocysteine remethylation and trans-sulfuration. Metabolism. 2004 Nov;53(11):1480-3. doi: 10.1016/j.metabol.2004.06.003.
PubMed 15536605Selhub 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.
PubMed 1728812Selhub 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.
PubMed 10475885Osganian 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.
PubMed 10199428Cheng 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.
PubMed 20051609Sato 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.
PubMed 24018893Satyanarayana 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.
PubMed 22069468Coppola 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.
PubMed 22425007Linnebank 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.
PubMed 21246600De 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.
PubMed 12884032Age limits and adolescents. Paediatr Child Health. 2003 Nov;8(9):577-8. doi: 10.1093/pch/8.9.577. No abstract available.
PubMed 20019831
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy Study of Folic Acid Supplementation on Homocysteine Levels in Adolescent Epileptics Taking Antiepileptic Drugs: A Single Blind Randomized Controlled Clinical Trial
- ClinicalTrials.gov ID
- NCT02318446
- Acronym / sponsor ID
- LTRG/E-1/03/ 1210
- Conditions
- Epilepsy
- Keywords
- Anti-epileptic drugs, Folic acid, Homocysteine
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Maharashtra University of Health SciencesUniversity, hospital or other
- Study start
- Mar 2015
- Primary completion
- Apr 2016 (estimated)
- Study completion
- May 2016 (estimated)
- First posted
- 17 Dec 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control group | Placebo comparator | Drug: SaccharineWill receive Oral saccharine tablet daily for 1month along with their existing antiepileptic therapy |
| Test group | Experimental | Drug: Folic AcidWill receive Oral Folic acid 1mg tablet daily for 1month along with their existing antiepileptic therapy |
Who may qualify
- Ages
- 10 to 19 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (2 listed)
- 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]
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Folic AcidAlso: FolviteTest group(n= 24) Existing Anti-epileptic Drugs + Oral Folic acid 1mg tablet daily for 1month | Drug | Test group |
| SaccharineAlso: Sugar freePlacebo group(n=12) Existing Anti-epileptic Drugs + Oral saccharine 10 mg tablet daily for 1month | Drug | Control group |
Primary outcome
Decrease in serum homocysteine levels by 2 µmol/l
Time frame: 1 month
2 secondary outcomes
Change in baseline serum lipids
Time frame: 1 month
Change in baseline systolic blood pressure
Time frame: 1 month
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2014.
- Background: PubMed 15536605Hoffer LJ. Homocysteine remethylation and trans-sulfuration. Metabolism. 2004 Nov;53(11):1480-3. doi: 10.1016/j.metabol.2004.06.003.
- Background: PubMed 1728812Selhub 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.
- Background: PubMed 10475885Selhub 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.
- Background: PubMed 10199428Osganian 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.
- Background: PubMed 20051609Cheng 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.
- Background: PubMed 24018893Sato 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.
- Background: PubMed 22069468Satyanarayana 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.
- Background: PubMed 22425007Coppola 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.
- Background: PubMed 21246600Linnebank 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.
- Background: PubMed 12884032De 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.
- Background: PubMed 20019831Age limits and adolescents. Paediatr Child Health. 2003 Nov;8(9):577-8. doi: 10.1093/pch/8.9.577. No abstract available.
- World Health Organization. \[Accessed May 15, 2014\]; Health topics. Adolescent health. 2011Link provided by the sponsor.
Related trials for Epilepsy
Not yet recruiting
Clinical Trial of SEEG for Drug-resistant Epilepsy
Drug-Resistant Epilepsy
RecruitingPhase 3
Investigate Efficacy and Safety of Carisbamate as Adjunctive Treatment for Seizures Associated With LGS in Children and Adults
Seizures, Lennox Gastaut Syndrome
RecruitingPhase 3
Study Evaluating the Efficacy and Safety of RAP-219 in Adult Participants With Focal Seizures
Focal Seizure, Epilepsy
Active, not recruitingObservational study
Transforming Research and Clinical Knowledge in Traumatic Brain Injury Epileptogenesis Project (TRACK-TBI EPI)
Traumatic Brain Injury, Post-traumatic Epilepsy
RecruitingPhase 3
Study Evaluating the Efficacy and Safety of RAP-219 in Adult Participants With Focal Seizures FOCUS-1
Focal Seizure, Epilepsy
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
UMA A. BHOSALE, MD principal investigator
Smt. Kashibai Navale Medical College and General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Folic Acid and Saccharine in people with Epilepsy, run by Maharashtra University of Health Sciences at 1 site in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 17 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact UMA A. BHOSALE, MD (02024106 ext. 148, umabhosale2000@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Decrease in serum homocysteine levels by 2 µmol/l (time frame: 1 month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02318446, which also lists 11 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2014.