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NCT04064814·Phase 4·INTERVENTIONAL

Evaluation of Efficacy and Safety of add-on Alpha-lipoic Acid on Migraine Prophylaxis in Adolescent Population

Status

Completed

Phase

Phase 4

Enrollment

60

Locations

1

Results

Not posted

Publications

11

Study summary

What the protocol is testing.

Migraine causes a substantial impact on the physical and mental health of a child and it is a major cause for time-off school leading to impaired academic performance. Therefore prophylactic treatment is suggested for adolescents with frequent or disabling migraine, aiming at improving the function, quality of life and reducing disability. The most commonly used non-pharmacological agents for the prophylactic management of migraine in adolescents are nutraceuticals. Amongst all nutraceuticals, most commonly used agents for prophylaxis are coenzyme Q10, magnesium, riboflavin, feverfew and butterbur . Alpha-lipoic acid (ALA) or 6,8-thioctic acid, is an endogenous molecule which functions as an important co-factor for various enzyme complexes in mitochondria and plays an important role in energy metabolism.ALA is a nutraceutical agent which also has neuroprotective and anti-inflammatory effects. It has been proved that the thiol level remains low in migraine patients. However, only one study has been done by Ali et al in the pediatric population where the combination of ALA and topiramate has shown promising results but the study result is not generalizable due to its inherent limitations. So, the study has been planned with an aim to evaluate the efficacy and safety of ALA as add-on therapy with flunarizine in the adolescent age group

Full detailed description

Migraine causes a substantial impact on the physical and mental health of a child and it is a major cause for time-off school leading to impaired academic performance. Therefore prophylactic treatment is suggested for adolescents with frequent or disabling migraine, aiming at improving the function, quality of life and reducing disability. Pharmacological agents commonly used for migraine prophylaxis in adolescents are topiramate, cyproheptadine, amitriptyline, valproate, propranolol and flunarizine. These preventive medications are effective first-line treatment but the associated adverse effects have limited their use amongst the adolescent population. In this clinical scenario nutraceuticals may be an alternative option. The most commonly used non-pharmacological agents for the prophylactic management of migraine in adolescents are nutraceuticals. Amongst all nutraceuticals, most commonly used agents for prophylaxis are coenzyme Q10, magnesium, riboflavin, feverfew and butterbur . Despite being largely used for prophylaxis of adolescent migraine, sufficient evidences are lacking which support the safety and efficacy of these agents. The findings from the previous studies on riboflavin and coenzyme Q10 are conflicting and inconclusive. Thus there is a need for a clinically effective nutraceutical in migraine prophylaxis. Alpha-lipoic acid (ALA) or 6,8-thioctic acid, is an endogenous molecule which functions as an important co-factor for various enzyme complexes in mitochondria and plays an important role in energy metabolism. ALA is a nutraceutical agent which also has neuroprotective and anti-inflammatory effects. It has been proved that the thiol level remains low in migraine patients. In some recent studies, ALA has been found to be beneficial in migraine prophylaxis in adults. However, only one study has been done by Ali et al in the pediatric population where the combination of ALA and topiramate has shown promising results but the study result is not generalizable due to its inherent limitations. From the literature search, it is evident that there is a lack of data on the efficacy and safety of ALA as a prophylactic agent in migraine. So, the study has been planned with an aim to evaluate the efficacy and safety of ALA as add-on therapy with flunarizine in the adolescent age group. The choice of flunarizine as standard prophylactic therapy in the present study is supported by the fact that flunarizine is efficacious and safer in the adolescent population due to its fewer adverse effects in comparison to topiramate and propranolol.

Interventions

Treatment arms and agents.

DRUG

Flunarizine 5mg

Flunarizine 5mg once daily,orally for 12 weeks

DRUG

Alpha lipoic acid 300mg

Alpha lipoic acid 300mg ,once daily ,orally for 12 weeks

Timeline

From registration to results.

  1. First posted

    Aug 22, 2019

  2. Study start

    Sep 14, 2019

  3. Primary completion

    Apr 30, 2021

  4. Study completion

    Jun 30, 2021

  5. Results posted

    Not reported

  6. Registry updated

    Jul 25, 2023

Outcomes

What the study measures.

Primary outcomes

Mean monthly migraine attack rate

Time frame · 12 weeks

Change in the mean monthly migraine attack rate from baseline after treatment with Flunarizine vs Alpha Lipoic Acid

Secondary outcomes

Responder rate

Time frame · 12 weeks

percentage of patients having ≥50% reduction in migraine frequency from baseline after treatment with Flunarizine vs Alpha Lipoic Acid

The number of days with migraine headache

Time frame · 12 weeks

The number of days with migraine headache from baseline after treatment with Flunarizine vs Alpha Lipoic Acid

The mean severity of acute attacks

Time frame · 12 weeks

The mean severity of acute attacks will be considered as severity basis where 3 will be severe and 1 will be mild attack (on a 3-point scale: 3, severe; 2, moderate; 1, mild) from baseline after treatment with Flunarizine vs Alpha Lipoic Acid

The number of days with nausea or vomiting

Time frame · 12 weeks

The number of days with nausea or vomiting from baseline after treatment with Flunarizine vs Alpha Lipoic Acid

The headache disability will be assessed by pedMIDAS (pediatric migraine disability assessment score)

Time frame · 12 weeks

The headache disability will be assessed by pedMIDAS (pediatric migraine disability assessment score) scoring system (denotes 0 to 10 as little to no dyability and greater than 50 as severe disability) from baseline after treatment with Flunarizine vs Alpha Lipoic Acid

The relapse rate among the responders after stoppage of prophylactic therapy .

Time frame · 12 weeks

The relapse rate among the responders after stoppage of prophylactic therapy over the next 12 weeks.

Serum thiol levels

Time frame · 12 weeks

Serum thiol levels from baseline after treatment with Flunarizine vs Alpha Lipoic Acid

Serum CGRP

Time frame · 12 weeks

Serum CGRPlevels from baseline after treatment with Flunarizine vs Alpha Lipoic Acid

Eligibility

Who can take part.

Minimum age
10 Years
Maximum age
19 Years
Sex
ALL
Healthy volunteers
No

Inclusion Criteria: * Patients with "15 or more headache days per month with at least 8 days having migraine features for at least 3 months (according to the criteria of the International Classification of Headache Disorders, 3rd edition \[beta version\], or ICHD-3 beta)." * Adolescent migraineurs aged 10 to 19 years of age of either sex. * Patients who have not taken any prophylactic treatment within the last three months before their inclusion in the study. * Patients and/or parents have given informed written consent/assent. Exclusion Criteria: * Patient with headache other than migraine. * Patients who were on corticosteroids * Treatment with any test drugs in the preceding three months from the start of the trial. * If there is any history of interventions or devices used for the treatment of migraine, such as transcranial magnetic stimulation and nerve blocks during the 3 months before screening. * Any other accompanying systemic illness; abnormalities revealed on neurologic examination. * Psychiatric disturbances, history of epilepsy , learning disabilities, head trauma or use of other drugs acting on the central nervous system, including, smoking, alcohol consumption or any illicit drug abuse

Study locations

1 registered sites.

India. Showing up to 24 locations stored in the fast local snapshot.

AIIMS

Bhubaneswar, Odisha, India

Publications

Results and literature.

PMID 28647791Karsan N, Prabhakar P, Goadsby PJ. Premonitory Symptoms of Migraine in Childhood and Adolescence. Curr Pain Headache Rep. 2017 Jul;21(7):34. doi: 10.1007/s11916-017-0631-y.PMID 17550953Eiland LS, Jenkins LS, Durham SH. Pediatric migraine: pharmacologic agents for prophylaxis. Ann Pharmacother. 2007 Jul;41(7):1181-90. doi: 10.1345/aph.1K049. Epub 2007 Jun 5.PMID 22500646O'Brien HL, Kabbouche MA, Hershey AD. Treating pediatric migraine: an expert opinion. Expert Opin Pharmacother. 2012 May;13(7):959-66. doi: 10.1517/14656566.2012.677434. Epub 2012 Apr 14.PMID 28527067D'Onofrio F, Raimo S, Spitaleri D, Casucci G, Bussone G. Usefulness of nutraceuticals in migraine prophylaxis. Neurol Sci. 2017 May;38(Suppl 1):117-120. doi: 10.1007/s10072-017-2901-1.PMID 23336811Wang J, Tang J, Zhou X, Xia Q. Physicochemical characterization, identification and improved photo-stability of alpha-lipoic acid-loaded nanostructured lipid carrier. Drug Dev Ind Pharm. 2014 Feb;40(2):201-10. doi: 10.3109/03639045.2012.753901. Epub 2013 Jan 22.PMID 17355494Magis D, Ambrosini A, Sandor P, Jacquy J, Laloux P, Schoenen J. A randomized double-blind placebo-controlled trial of thioctic acid in migraine prophylaxis. Headache. 2007 Jan;47(1):52-7. doi: 10.1111/j.1526-4610.2006.00626.x.PMID 3282670Sorge F, De Simone R, Marano E, Nolano M, Orefice G, Carrieri P. Flunarizine in prophylaxis of childhood migraine. A double-blind, placebo-controlled, crossover study. Cephalalgia. 1988 Mar;8(1):1-6. doi: 10.1046/j.1468-2982.1988.0801001.x.PMID 30947525Abu-Arafeh I, Hershey AD, Diener HC, Tassorelli C; Clinical Trials Standing Committee and the Child and Adolescent Standing Committee of the International Headache Society. Guidelines of the International Headache Society for controlled trials of preventive treatment of migraine in children and adolescents, 1st edition. Cephalalgia. 2019 Jun;39(7):803-816. doi: 10.1177/0333102419842188. Epub 2019 Apr 4.PMID 2861907Sorge F, Marano E. Flunarizine v. placebo in childhood migraine. A double-blind study. Cephalalgia. 1985 May;5 Suppl 2:145-8. doi: 10.1177/03331024850050S227.PMID 26923752Kenney D, Jenkins S, Youssef P, Kotagal S. Patient Use of Complementary and Alternative Medicines in an Outpatient Pediatric Neurology Clinic. Pediatr Neurol. 2016 May;58:48-52.e7. doi: 10.1016/j.pediatrneurol.2015.11.003. Epub 2016 Jan 11.PMID 37563914Puliappadamb HM, Satpathy AK, Mishra BR, Maiti R, Jena M. Evaluation of Safety and Efficacy of Add-on Alpha-Lipoic Acid on Migraine Prophylaxis in an Adolescent Population: A Randomized Controlled Trial. J Clin Pharmacol. 2023 Dec;63(12):1398-1407. doi: 10.1002/jcph.2331. Epub 2023 Aug 24.

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