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

Sponsor

All India Institute of Medical Sciences, Bhubaneswar (Other)

Overall Status

Recruiting

CT.gov ID

NCT04064814

Collaborator

(none)

Enrollment

Location

Arms

25.5

Anticipated Duration (Months)

2.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Adolescent Migraine	Drug: Flunarizine 5mg Drug: Alpha lipoic acid 300mg	Phase 4

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Randomized, open Label , active controlled studyRandomized, open Label , active controlled study

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

Evaluation of Efficacy and Safety of add-on Alpha-lipoic Acid on Migraine Prophylaxis in Adolescent Population: A Randomized Controlled Trial

Actual Study Start Date :

Sep 14, 2019

Actual Primary Completion Date :

Apr 30, 2021

Anticipated Study Completion Date :

Oct 30, 2021

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Flunarizine flunarizine will be prescribed at a dose of 5mg once daily , orally for 12 weeks	Drug: Flunarizine 5mg Flunarizine 5mg once daily,orally for 12 weeks
Experimental: Alpha Lipoic Acid Alpha Lipoic Acid will be prescribed at a dose of 300mg once daily,orally for 12 weeks	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

Arm

Intervention/Treatment

Active Comparator: Flunarizine

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

Drug: Flunarizine 5mg

Flunarizine 5mg once daily,orally for 12 weeks

Experimental: Alpha Lipoic Acid

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

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

Outcome Measures

Primary Outcome Measures

Mean monthly migraine attack rate [12 weeks]
Change in the mean monthly migraine attack rate from baseline after treatment with Flunarizine vs Alpha Lipoic Acid

Secondary Outcome Measures

Responder rate [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 [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 [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 [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) [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 . [12 weeks]
The relapse rate among the responders after stoppage of prophylactic therapy over the next 12 weeks.
Serum thiol levels [12 weeks]
Serum thiol levels from baseline after treatment with Flunarizine vs Alpha Lipoic Acid
Serum CGRP [12 weeks]
Serum CGRPlevels from baseline after treatment with Flunarizine vs Alpha Lipoic Acid

Eligibility Criteria

Criteria

Ages Eligible for Study:

10 Years to 19 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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