Prediction of Migraine Prevention Efficacy Based on Individual's Pain Modulation

Study Overview
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Brief Summary
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A major reason for the substantial underuse of pharmacological prevention of migraine is its inadequate efficacy, since only  50% of patients respond to a specific agent. There is currently no evidence-based way to identify the patients that will respond to a specific preventive treatment. Amitriptyline is one of the commonest agents used for migraine prevention, strengthening patient's pain inhibitory capacity. Individual tailoring of analgesics according to pain inhibitory capacity has been shown effective by our group for painful diabetic neuropathy patients. Specifically, patients with reduced pain inhibition capacity gained more from a drug that augment pain inhibition as compared to those with efficient inhibitory capacity. The investigators now propose to assess migraineurs for their pain inhibition capacity, and examine whether, along similar reasoning, those with reduced inhibitory capacity are the ones more likely to respond to amitriptyline. Psychophysical and neurophysiological dimensions of pain inhibitory modulation will be assessed in migraineurs, who will, subsequently, receive either amitriptyline or placebo for 8 weeks, in a randomized two arms parallel double blind design, and followed up for attacks reduction. The investigators expect to identify the best predictors for efficacy of migraine prevention by the study drug. This approach will promote individualization of migraine therapy.

Official Title
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Prediction of Migraine Prevention Efficacy: Individualization of Treatment by Coupling Drug's Mode of Action With Patient's Mechanism of Pain Modulation

Conditions
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Migraine, Preventive Treatment

Intervention / Treatment
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* Drug: Amitriptyline
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age >18 premenopausal meeting the international headache society criteria for migraine having >4 attacks or days of migraine/month Exclusion Criteria: baseline month diary indicating lower frequency of migraine chronic migraine (>15 days of headache per month) use of migraine preventive treatment during previous 3 month language barrier or cognitive dysfunction

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Amitriptyline<br>Amitriptyline, 25 mg per os, daily, evening, for 8 weeks; starting dose is 12.5 mg for 2 days | Drug: placebo<br>* per os, daily, evening<br>* Other names: sugar pills;|
| Placebo Comparator: placebo<br>sugar pills | Drug: Amitriptyline<br>* per os, daily, evening<br>* Other names: Elatrol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| predictive value of the pre-treatment pain measures parameter(s) for benefit from amitriptyline treatment | ANCOVA will be utilized, based on factors treatment (amitriptyline or placebo), conditioned pain modulation capabilities (responder or non-responder), their interaction, a number of covariates, to predict reduction attacks. | one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| predictive value of pain-related psychological parameters for benefit from amitriptyline treatment | The scores for Spielberger's anxiety state and trait questionnaire, and for pain catastrophising questionnaire will be used. | one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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migraine, Amitriptyline, pain modulation, pain psychophysics, pain neurophysiology, preventive treatment