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

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

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.

Study Overview

• Status: Completed
• Conditions: Migraine
• Intervention / Treatment: Drug: 5-ISMN (isosorbide-5-mononitrate); Drug: Sumatriptan; Drug: Placebo

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Glostrup
    • Copenhagen, Glostrup, Denmark, 2600
      • Emma Katrine Hansen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Sumatriptan; 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); 5-ISMN is given both study days to induce headache. One day the headache is treated with placebo and the other day with sumatriptan; Other Names: Imdur; Drug: Sumatriptan; 5-ISMN is given both study days to induce headache. One day the headache is treated with placebo and the other day with sumatriptan; Other Names: Imigran
Placebo Comparator: Placebo; 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); 5-ISMN is given both study days to induce headache. One day the headache is treated with placebo and the other day with sumatriptan; Other Names: Imdur; Drug: Placebo; 5-ISMN is given both study days to induce headache. One day the headache is treated with placebo and the other day with sumatriptan

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Danish Headache Center

Study record dates

Study Major Dates

• Study Start: April 1, 2015
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: June 4, 2015
• First Submitted That Met QC Criteria: June 26, 2015
• First Posted (Estimate): June 30, 2015

Study Record Updates

• Last Update Posted (Estimate): January 22, 2016
• Last Update Submitted That Met QC Criteria: January 21, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Headache; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Natriuretic Agents; Serotonin Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Diuretics, Osmotic; Diuretics; Vasoconstrictor Agents; Nitric Oxide Donors; Isosorbide; Isosorbide Dinitrate; Isosorbide-5-mononitrate; Sumatriptan
• Other Study ID Numbers: H-6-2014-071