The human NTG model of migraine in drug discovery and development

ABSTRACT

Introduction

Various triggers can originate a migraine attack. In healthy volunteers and patients with migraine, the nitroglycerin (NTG) provocation model induces a headache that resembles migraine in pain characteristics and vascular manifestations. This headache is reversible and treatable in monitored conditions, providing an opportunity to test novel antimigraine medications in early clinical development.

Areas covered

This perspective covers the main characteristics and applications of the human NTG model of migraine with effective and ineffective antimigraine therapies.

Expert opinion

The NTG model represents a potential de-risking strategy to test novel hypotheses for antimigraine mechanisms in humans. Considering previous studies conducted with effective and ineffective antimigraine therapies, the sensitivity of the model was 71% while the specificity was 100%. The probability that following an analgesic effect, that compound would truly be efficacious in individuals with migraine was 100%. Following a negative result, the probability that such compound would truly be ineffective in patients with individuals was 33%. A clinical trial testing the analgesic properties of novel compounds after a sublingual and/or intravenous NTG challenge in migraine patients may support a subsequent phase 2 trial for the treatment of migraine.

KEYWORDS:

• CGRP
• headache
• nitroglycerin
• pain
• vascular model

Article highlights

• Nitroglycerin (NTG) is the most reliable trigger provoking migraine-like headaches in patients with migraine.

• The human NTG model has been tested with effective and ineffective antimigraine therapies.

• The sensitivity of the human NTG model was 71%, while the specificity was 100%.

• The positive predictive value of the human NTG model was 100%, while the negative predictive value was 33%.

• The NTG model might be an operational de-risking tool in clinical development for future migraine therapies.

Acknowledgments

The author would like to acknowledge Dr. Tolga Uz for his precious suggestions and comments.

Declaration of interest

L Pellesi is an employee of Lundbeck A/S. He has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was not funded.