The Effect of Sumatriptan and Placebo on Isosorbide-5-mononitrate Induced Headache

Study Overview
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Brief Summary
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To develop a pragmatic migraine model the investigators will induce headache in healthy volunteers and in patients with migraine without aura with a long lasting Nitrogen Oxide (NO) donor. If the headache responds to sumatriptan, the model can be used to test new drug candidates.

Detailed Description
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There remains a great need for more effective anti-migraine drugs with fewer side effects. Human experimental models are valuable in early phase development of new anti-migraine drugs but useful models have not yet been developed. The investigators' group has shown that Isosorbide-5-mononitrate (5-ISMN), a long lasting NO-donor, induce headache/migraine in both healthy volunteers and in patients with migraine without aura (MO). To validate this model, the headache must respond to specific migraine treatment with sumatriptan. Hypothesis: 5-ISMN induces a migraine-like headache in both healthy subjects and in MO-patients and induced headache responds to a specific anti migraine drug; sumatriptan. Aim: Developing a pragmatic and valid model for the testing of new anti-migraine drugs

Official Title
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The Effect of Sumatriptan and Placebo on Isosorbide-5-mononitrate Induced Headache. Development of a Pragmatic Migraine Model

Conditions
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Migraine

Intervention / Treatment
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* Drug: 5-ISMN (isosorbide-5-mononitrate)
* Drug: Sumatriptan
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy: healthy subjects of both sexes age 18-70 years weight 50-90 kg. Females were requested to use effective contraception. Migraine patients: Migraine patients who meet International headache society (IHS) criteria for migraine with or without aura of both sexes 18-70 years 45-95 kg. Exclusion Criteria: Healthy: Any type of headache (except episodic tension-type headache < 1 day per week) Serious somatic or psychiatric disease Pregnancy Intake of daily medication (except oral contraceptives). Migraine patients: Any other type of headache then migraine without aura (except episodic tension-type headache < 1 day per week) Serious somatic or psychiatric disease Pregnancy, and intake of daily medication (except oral contraceptives).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sumatriptan<br>headache is induced with 5-ISMN. This headache is treated double-blinded with 1 tablet of sumatriptan 50 mg | Drug: 5-ISMN (isosorbide-5-mononitrate)<br>* 5-ISMN is given both study days to induce headache. One day the headache is treated with placebo and the other day with sumatriptan<br>* Other names: Imdur;Drug: Sumatriptan<br>* 5-ISMN is given both study days to induce headache. One day the headache is treated with placebo and the other day with sumatriptan<br>* Other names: Imigran;|
| Placebo Comparator: Placebo<br>headache is induced with 5-ISMN. This headache is treated double-blinded with 1 tablet of placebo (the tablet is similar to the active tablet) | Drug: 5-ISMN (isosorbide-5-mononitrate)<br>* 5-ISMN is given both study days to induce headache. One day the headache is treated with placebo and the other day with sumatriptan<br>* Other names: Imdur;Drug: Placebo<br>* 5-ISMN is given both study days to induce headache. One day the headache is treated with placebo and the other day with sumatriptan<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median headache score 0 hours after sumatriptan/placebo |  | 0 hours | 
| Median headache score 2 hours after sumatriptan/placebo |  | 2 hours |