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

NCT ID: NCT04064814

Last Updated: 2023-07-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-14
• Study Completion Date: 2021-06-30

Brief Summary

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

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.

Conditions

Adolescent Migraine

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Flunarizine

flunarizine will be prescribed at a dose of 5mg once daily , orally for 12 weeks

Group Type: ACTIVE_COMPARATOR

Flunarizine 5mg

Intervention Type: DRUG

Flunarizine 5mg once daily,orally for 12 weeks

Alpha Lipoic Acid

Alpha Lipoic Acid will be prescribed at a dose of 300mg once daily,orally for 12 weeks

Group Type: EXPERIMENTAL

Flunarizine 5mg

Intervention Type: DRUG

Flunarizine 5mg once daily,orally for 12 weeks

Alpha lipoic acid 300mg

Intervention Type: DRUG

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

Interventions

Flunarizine 5mg

Flunarizine 5mg once daily,orally for 12 weeks

Intervention Type: DRUG

Alpha lipoic acid 300mg

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

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 10 Years
• Maximum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

All India Institute of Medical Sciences, Bhubaneswar

OTHER

Sponsor Role: lead

Responsible Party

Dr. Monalisa Jena, M.D.

Assistant professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Rituparna Maiti, MD

Role: STUDY_DIRECTOR

Additional Professor

Locations

AIIMS

Bhubaneswar, Odisha, India

Countries

India

References

Karsan 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.

Reference Type: BACKGROUND

PMID: 28647791 (View on PubMed)

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Reference Type: BACKGROUND

PMID: 17550953 (View on PubMed)

O'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.

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Reference Type: BACKGROUND

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Sorge 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.

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Reference Type: BACKGROUND

PMID: 26923752 (View on PubMed)

Puliappadamb 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.

Reference Type: DERIVED

PMID: 37563914 (View on PubMed)

Other Identifiers

AIIMSBBSR/PGThesis/2019-20/15

Identifier Type: -

Identifier Source: org_study_id