Effectiveness and Neural Mechanism of Naoan Dripping Pills for Migraine

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled clinical trial. Its main purpose is to investigate the effects and neural mechanism of Naoan dripping pills on migraine patients by utilizing fMRI and DTI method, as well as headache evaluation measures such as responder rate, headache duration, PRO scale, etc.

Detailed Description
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Naoan dripping pills, which is a Chinese patent medicine proved effectively in treating migraine on clinic, but its neural mechanism remains unknown. This study is expected to validate the effectiveness and explore its neural mechanism by fMRI and DTI so as to provide evidence for physicians to promote the appropriate use of Naoan dripping pills treatment for migraine patients. Patients will be randomly assigned to either Naoan dripping pills group or placebo group, they will receive Naoan dripping pills/Placebo treatment for 12 weeks. Clinical evaluation will be performed at baseline, every 4 weeks during treatment and the follow-up week(16 weeks) . MRI scans are performed at baseline, and 12 weeks later. Responder rate (defined as the percentage of subjects in a treatment group with 50 % or greater reduction in attack frequency during treatment compared with the baseline period) and fMRI and DTI imaging changes after treatment are defined as primary outcome. In addition, 10 healthy controls will also undergo MRI scanning at baseline to determine abnormal brain activity and structure in migraine patients.

Official Title
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Effectiveness and Neural Mechanism of Naoan Dripping Pills for Migraine: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Conditions
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Migraine

Intervention / Treatment
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* Drug: Naoan dripping pills
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has migraine without aura or with typical aura according to criteria of the International Headache Society (IHS) Subject has been diagnosed with qi deficiency syndrome and/or blood stasis syndrome in TCM Subject has onset of migraine occurring before age 50 Subject has a history of migraine headaches for at least 1 year In recent 3 months, subject has 2 to 8 headache attacks every 4 weeks Age ≥ 18 years and ≤ 65 years Right-handers Subject has signed informed consent Exclusion Criteria: Subject takes painkillers more than 10 days a month for headache attacks Subject who was／is in possess of Naoan dripping pills therapy but the treatment is ineffective Allergic to Naoan dripping pills subject's taken, within 12 weeks before enrollment, migraine prevention drugs drugs such as β-blocker, calcium channel inhibitor，Anti-epileptic drugs，antidepressants or 5-HT receptor blocker Alcohol or drug abusers Subject suffers from other primary headaches as specified by IHS criteria Subject has medical condition such as severe heart disease, stroke, kidney disease, liver disease, hepatic or renal impairment, hematologic disease Subject has psychological or mental disorder, Hamilton Anxiety Scale（HAMA）≥7，Hamilton Depression Scale（HAMD）≥7 Subject has language impairment or cognitive impairment, unable to read, understand or record information in study diaries and questionnaires Pregnant or breast feeding subjects Subjects with contraindications for undergoing MRI scans (e.g. Claustrophobic, patients with heart pacemaker )

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Naoan dripping pills for migraine<br>Drug: Naoan dripping pills, Chinese patent medicine，pill. Patients will receive treatment with Naoan dripping pills for 12 weeks, Fenbid can be taken if headache is unbearable Procedure: MRI scanning（fMRI and DTI） | Drug: Naoan dripping pills<br>* Patients will take 20 pills(1000mg) after meal twice a day for 12 weeks, Fenbid can be taken if headache is unbearable, but make sure the records(including attack time, drug dosage, pain intensity and duration) are written down as detailed as possible. Procedure: MRI scanning (fMRI and DTI）<br>|
| Placebo Comparator: Placebo<br>Drug: Placebo, pill. Patients will receive treatment with placebo for 12 weeks, Fenbid can be taken if headache is unbearable Procedure: MRI scanning （fMRI and DTI） | Drug: Placebo<br>* Patients will take 20 pills(1000mg) after meal twice a day for 12 weeks, Fenbid can be taken if headache is unbearable, but make sure the records(including attack time, drug dosage, pain intensity and duration) are written down as detailed as possible. Procedure: MRI scanning (fMRI and DTI)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Responder rate | Defined as the percentage of subjects in a treatment group with 50 % or greater reduction in attack frequency during treatment compared with the baseline period | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in functional connectivity assessed by Resting-state fMRI | Investigate the differences in fractional anisotropy of migraine patients compared to healthy volunteers at baseline, and compare the changes of fractional anisotropy after 12 weeks' treatment in two groups | Baseline and 12 weeks | 
| Change in fractional anisotropy (FA) assessed by DTI | Investigate the differences in fractional anisotropy of migraine patients compared to healthy volunteers at baseline, and compare the changes of fractional anisotropy after 12 weeks' treatment in two groups | Baseline and 12 weeks | 
| Duration of migraine attacks | To compare the reduction of duration of migraine attacks after 12 weeks' treatment in two groups | 12 weeks and 16 weeks | 
| Intensity of headache | To compare the change of the duration of migraine attacks (mild, moderate, severe) after 12 weeks' treatment in two groups | 12 weeks and 16 weeks | 
| Patient reported outcome (PRO) scale of migraine | To compare the change of Patient reported scores after 12 weeks' treatment in two groups | 12 weeks and 16 weeks | 
| Number of migraine days per evaluation interval | To compare the reduction of the number of migraine days per evaluation interval after 12 weeks' treatment in two groups | 12 weeks and 16 weeks | 
| Drug consumption for symptomatic or acute treatment | To compare the change of drug consumption for symptomatic or acute treatment after 12 weeks' treatment in two groups | 12 weeks and 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Migraine, Naoan dripping pills, Traditional Chinese Medicine, fMRI, Randomized Controlled trial