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The investigators hypothesized that migraine without patients with many genetic loci associated with migraine (high genetic load) would be more sensitive and get provoked more migraine attacks by calcitonin gene-related peptide (CGRP) compared to patients with few genetic loci associated with migraine (low genetic load).
Migraine is a very prevalent neurological disorder with a strong genetic factor. The common forms of migraine have a multifactorial and polygenic pattern of inheritance and genetics research is crucial for a deeper understanding of migraine mechanisms. Recently, 12 genetic loci have been identified to be associated with migraine with (MA) and without aura (MA) in four large genome-wide association studies (GWAS). The functional consequences of these genetic loci in humans are yet unknown.
Calcitonin gene-related peptide (CGRP) is a neuropeptide which plays a crucial role in the pathophysiology of migraine and is present in migraine relevant structures. CGRP can induce migraine attacks in MO patients via an adenosine monophosphate (cAMP) dependent pathway and CGRP antagonism is efficient in the treatment of migraine attacks. Also, a recent study has showed that intracellular accumulation of cAMP is crucial for the induction of migraine attacks. However, CGRP does not cause migraine attacks in familial hemiplegic migraine (FHM), an autosomal dominant subtype of MA.
The phenotype of the migraine inducing effects of CGRP might therefore be linked to some of the 12 genetic susceptibility loci that have been identified. One of the genetic loci (rs13208321) is located in a gene (FHL5) that is associated with the regulation of cAMP-responsive elements.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Migraine patients with high genetic load | Active Comparator | CGRP intravenous infusion 1.5 microgram/min for 20 min |
|
| Migraine patients with low genetic load | Active Comparator | CGRP intravenous infusion 1.5 microgram/min for 20 min |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CGRP | Drug | Calcitonin-gene-related-peptide (CGRP) |
|
| Measure | Description | Time Frame |
|---|---|---|
| CGRP induced migraine attacks in patients with high and low genetic load | The difference in incidence of migraine-like attacks between patients with high genetic load and patients with low genetic load using verbal rating scale (VRS). | Change from baseline in headache intensity at 12 hours after the start of infusion of CGRP |
| Measure | Description | Time Frame |
|---|---|---|
| CGRP induced migraine attacks in patients with high and low genetic load | The difference in area under the curve (AUC) for headache intensity scores (0-12 hours) | Change from baseline in headache intensity at 12 hours after the start of infusion of CGRP |
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Inclusion Criteria:
- Migraine without aura patients genotyped for the 12 newly idetified gene variants associated with migraine.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Song Guo, MD | Danish Headache Center & Department of Neurology | Principal Investigator |
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| Type | Date | Date Unknown |
|---|---|---|
| Release | Aug 6, 2024 | |
| Reset | Aug 26, 2024 |
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| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| Aug 6, 2024 | Aug 26, 2024 |
| ID | Term |
|---|---|
| D020326 | Migraine without Aura |
| ID | Term |
|---|---|
| D008881 | Migraine Disorders |
| D051270 | Headache Disorders, Primary |
| D020773 | Headache Disorders |
| D001927 | Brain Diseases |
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| ID | Term |
|---|---|
| D002116 | Calcitonin |
| ID | Term |
|---|---|
| D036361 | Peptide Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D013963 | Thyroid Hormones |
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| D002493 |
| Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D009479 | Neuropeptides |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D009419 | Nerve Tissue Proteins |
| D011506 | Proteins |