Candesartan Versus Propranolol for Migraine Prevention

Study Overview
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Brief Summary
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The main aim of the present study is to compare candesartan with propranolol for migraine prophylaxis.

Detailed Description
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Candesartan was shown to be effective for migraine prophylaxis in a randomized double blind cross-over study published in 2003. The drug is now widely used for this purpose in many countries, although no confirmatory study has been published. The aims of the present study are: 1) to see if the results in the first candesartan study can be replicated in a new patient population, including patients with chronic migraine, and, 2) to perform a head-to-head comparison of candesartan 16 mg/day with standard treatment with propranolol 160 mg slow release. We also intend to study whether responsiveness to these drugs may be related to heart rate variability and baroreceptor sensitivity.

Official Title
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Candesartan vs Propranolol for Migraine Prevention: A Double Blind, Placebo Controlled, Double Dummy, Triple Cross-over Study

Conditions
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Migraine Without Aura, Migraine With Aura, Chronic Migraine

Intervention / Treatment
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* Drug: Candesartan
* Drug: propranolol
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age 18 to 65 years retrospectively have ≥ 2 migraine attacks per month during the last 3 months during the baseline period have ≥ 2 migraine attacks debut of migraine at least one year prior to inclusion start of migraine before age 50 years. Exclusion Criteria: interval headache not distinguishable from migraine chronic tension-type headache or other headache occurring on ≥ 15 days/month pregnancy, nursing or inability to use contraceptives heart conduction block on ECG or significant ECG abnormality on inclusion heart rate < 54 after 3 minutes rest previous or present asthma, diabetes; decreased hepatic or renal function hypersensitivity to active substance history of angioneurotic edema significant psychiatric illness use of daily migraine prophylactics less than 4 weeks prior to start of study having tried ≥ 3 prophylactic drugs against migraine during the last 10 years previous use of propranolol or candesartan in adequate doses previous discontinuation of either Atacand or Inderal Retard (or another beta blocker) due to side effects current use of antihypertensive medication require use of rizatriptan (Maxalt) 10 mg tabl. subjects requiring detoxification from acute medication (ergotamines, opioids) patients who consistently fail to respond to any acute migraine medication patients with alcohol or illicit drug dependence

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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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1 Candesartan<br> | Drug: Candesartan<br>* Candesartan cilexitil tablets, 16 mg once daily<br>|
| Active Comparator: 2 propranolol<br> | Drug: propranolol<br>* Propranolol hydrochloride capsules 160 mg once daily, slow release formulation<br>|
| Placebo Comparator: 3 Placebo<br> | Drug: placebo<br>* placebo tablets and capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of days per 4 weeks with moderate or severe headache lasting ≥ 4 hours or is treated with the patient's usual headache medication |  | One year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Days with headache |  | One year | 
| Hours with headache |  | One year | 
| Headache intensity (0-3 scale) on days with headache |  | one year | 
| Doses of analgesics |  | one year | 
| Doses of triptans |  | One year | 
| Days with sick leave |  | one year | 
| Number of responders (≥ 50% decrease in migraine days compared with baseline) |  | one year | 
| Number of reported side effects |  | one year | 
| Number of predefined retrospective side effects |  | one year |