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Investigators aim to compare the effect of valproate versus topiramate in migraine by assessing the reduction in MMD in each group, the percentage of patients who achieved ≥ 50% reduction in the monthly headache days frequency compared to the baseline frequency.
Investigators will enroll 600 migraine patients who are diagnosed according to ICHD3-beta criteria in our study and will use a questionnaire to detect their demographic and clinical features (disease duration, attack frequency, and duration, pain intensity assessed by the visual analogic scale and we have two groups the first group will include 300 patients and will receive 500-1000mg valproate daily and Acetaminophen 500-1000 mg in acute attack, and the second group will receive topiramate100 mg per day and Acetaminophen 500-1000 mg in acute attack for at least three months. Investigators will assess The number of migraine days after three months of treatment and the percentage of patients who achieved ≥ 50% reduction in the monthly headache days frequency compared to the baseline frequency (14).. HIT-6 score reduction in each group after three months of treatment. The safety of treatment was evaluated by monitoring and documenting treatment-emergent adverse events (TEAE) in patients through regular follow-up procedures for three months.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| valproate arm | Active Comparator | The arm will include 300 migraine patients diagnosed according to ICHD3-beta criteria. All patients will receive valproate 500-1000mg daily and Acetaminophen 500-1000 mg only in acute migraine attacks for 3 months. We will assess The change in migraine days per 28 days, the number of migraine days after three months of treatment, and the percentage of patients who achieved ≥ 50% reduction in the monthly headache days frequency compared to the baseline frequency (14). HIT-6 score reduction in each group after three months of treatment. The safety of valproate was evaluated by monitoring and documenting treatment-emergent adverse events (TEAE) in patients through regular follow-up procedures for three months. |
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| topiramate arm | Active Comparator | The arm will include 300 migraine patients diagnosed according to ICHD3-beta criteria. All patients will receive topiramate 50-100mg daily and Acetaminophen 500-1000 mg only in acute migraine attacks for 3 months. We will assess The change in migraine days per 28 days, the number of migraine days after three months of treatment, and the percentage of patients who achieved ≥ 50% reduction in the monthly headache days frequency compared to the baseline frequency (14). HIT-6 score reduction in each group after three months of treatment. The safety of valproate was evaluated by monitoring and documenting treatment-emergent adverse events (TEAE) in patients through regular follow-up procedures for three months. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Valproic acid | Drug | The arm will include 300 migraine patients diagnosed according to ICHD3-beta criteria. All patients will receive valproate 500-1000 mg daily and Acetaminophen 500-1000 mg only in acute migraine attacks for 3 months. We will assess The change in migraine days per 28 days, the number of migraine days after three months of treatment, and the percentage of patients who achieved ≥ 50% reduction in the monthly headache days frequency compared to the baseline frequency (14). HIT-6 score reduction in each group after three months of treatment. The safety of valproate was evaluated by monitoring and documenting treatment-emergent adverse events (TEAE) in patients through regular follow-up procedures for three months. |
| Measure | Description | Time Frame |
|---|---|---|
| The percentage of patients who achieved ≥ 50% change in the monthly migraine days frequency compared to the baseline frequency. | We will assess The percentage of patients who achieved ≥ 50% change in the monthly headache days frequency compared to the baseline frequency in each group | 3 months |
| The number of patients who discontinued treatment due to treatment-emergent adverse events. | The investigator will assess The number of patients who discontinued treatment due to treatment-emergent adverse events in each group after 3 months of treatment | 90 days |
| Measure | Description | Time Frame |
|---|---|---|
| The severity of migraine attack on VAS score after three months of treatment | After three months of treatment, the investigators will assess the severity of migraine attacks on VAS scores. VAS is scale from one to ten where one is the least severe pain while ten is the severest pain | 3 months |
| HIT-6 score change in each group after three months of treatment |
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Inclusion Criteria:
Naive migraine patients, according to the International Classification of Headache Disorders 3rd edition, aged 18-75 years,
Exclusion Criteria
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| Name | Affiliation | Role |
|---|---|---|
| mohamed G. Zeinhom, MD,PHD | neurology department kafr el-sheikh university | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Kafr Elsheikh University Hospital | Kafr ash Shaykh | 33155 | Egypt |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 11914403 | Result | Lipton RB, Scher AI, Kolodner K, Liberman J, Steiner TJ, Stewart WF. Migraine in the United States: epidemiology and patterns of health care use. Neurology. 2002 Mar 26;58(6):885-94. doi: 10.1212/wnl.58.6.885. | |
| 12807523 | Result | Lipton RB, Liberman JN, Kolodner KB, Bigal ME, Dowson A, Stewart WF. Migraine headache disability and health-related quality-of-life: a population-based case-control study from England. Cephalalgia. 2003 Jul;23(6):441-50. doi: 10.1046/j.1468-2982.2003.00546.x. |
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All the data supporting this research's findings may be available from the principal investigator Mohamed G. Zeinhom upon reasonable request.
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| ID | Term |
|---|---|
| D008881 | Migraine Disorders |
| ID | Term |
|---|---|
| D051270 | Headache Disorders, Primary |
| D020773 | Headache Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| D014635 | Valproic Acid |
| D000077236 | Topiramate |
| ID | Term |
|---|---|
| D010421 | Pentanoic Acids |
| D014631 | Valerates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
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We will assess The number of migraine days after three months of treatment, and the percentage of patients who achieved ≥ 50% reduction in the monthly headache days frequency compared to the baseline frequency (14). HIT-6 score reduction in each group after three months of treatment. The safety of treatment was evaluated by monitoring and documenting treatment-emergent adverse events (TEAE) in patients through regular follow-up procedures for three months.
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An independent statistician generated a blocked randomization sequence using computer-generated random numbers; participants received either valproate or topiramate from a specially trained and qualified nurse. We prepared Sequentially numbered opaque sealed envelopes and 600 labels for each drug labeled Drug A or B. According to the randomization chart, put them into envelopes numbered 1 to 600. Envelopes were attached to the patient's files. Patients were recruited sequentially and were given enrolment numbers starting from 1, which were mentioned on their files. Files with the same number as the patient enrolment number were opened and the patients were assigned to receive drugs A or B. Drug A included topiramate, and Drug B included valproate. The statistical analysis was performed by an independent statistician who did not know the treatment protocol of groups A or B.
|
|
| Topiramate 50 MG | Drug | The arm will include 300 migraine patients diagnosed according to ICHD3-beta criteria. All patients will receive topiramate 50-100 mg daily and Acetaminophen 500-1000 mg only in acute migraine attacks for 3 months. We will assess The change in migraine days per 28 days, the number of migraine days after three months of treatment, and the percentage of patients who achieved ≥ 50% reduction in the monthly headache days frequency compared to the baseline frequency (14). HIT-6 score reduction in each group after three months of treatment. The safety of topiramate was evaluated by monitoring and documenting treatment-emergent adverse events (TEAE) in patients through regular follow-up procedures for three months. |
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The investigators assessed the absolute change in HIT6 score, the Headache Impact Test-6 (HIT-6) assessed the burden of headache in each group; the HIT-6 consists of six items: pain, social functioning, role functioning, vitality, cognitive functioning, and psychological distress, the patient answers each of the six related questions using one of the following five responses: "never", "rarely", "sometimes", "very often," or "always." These responses are summed to produce a total HIT-6 score that ranges from 36 to 78, where a higher score indicates a greater impact of headache on the daily life of the respondent. It has four impact grades: little-to-no impact (HIT-6 score: 36-49), moderate impact (HIT-6 score: 50-55), substantial impact (HIT-6 score: 56-59), and severe impact (HIT-6 score: 60-78) |
| 3 months |
| Treatment safety was evaluated by monitoring treatment-emergent adverse events (TEAE) for three months. | The safety of treatment was evaluated by monitoring and documenting treatment-emergent adverse events (TEAE) in patients through regular follow-up procedures for three months. | 3 months |
| The monthly migraine days per month | The investigators will assess the change in migraine days per month in each group. | 30 days |
| The duration of migraine attack in hours after three months of treatment | After three months of treatment, the investigators will assess the duration of migraine attacks in hours in each group | 3 months |
| 8984084 | Result | Mushet GR, Miller D, Clements B, Pait G, Gutterman DL. Impact of sumatriptan on workplace productivity, nonwork activities, and health-related quality of life among hospital employees with migraine. Headache. 1996 Mar;36(3):137-43. doi: 10.1046/j.1526-4610.1996.3603137.x. |
| 40020561 | Derived | Zeinhom MG, Elsayed Khalil MF, Omar Youssif TY, Ali Daabis AM, Almoataz M, Refat HM, Mohamed Kamal Ebied AA, Atiaa Mohamed DM, Ismaiel M, Mohamed Kamel IF, Elballat AIE, Omar Akl AZ, Ahmed SR. Efficacy and tolerability of valproate versus topiramate in migraine prevention, a randomized controlled multi-center trial. J Clin Neurosci. 2025 May;135:111156. doi: 10.1016/j.jocn.2025.111156. Epub 2025 Feb 27. |
| D009422 | Nervous System Diseases |
| D009930 |
| Organic Chemicals |
| D005232 | Fatty Acids, Volatile |
| D005227 | Fatty Acids |
| D008055 | Lipids |
| D005632 | Fructose |
| D006601 | Hexoses |
| D009005 | Monosaccharides |
| D000073893 | Sugars |
| D002241 | Carbohydrates |
| D007661 | Ketoses |