Clinical Trial: Study of the Safety and Effectiveness of NXN-188 for the Acute Treatment of Migraine Attacks With Aura

Study Status: Completed
Recruit Status: Unknown status
Study Type: Interventional

Official Title: A Phase 2a Study of the Safety and Effectiveness of NXN-188 for the Acute Treatment of Migraine Attacks With Aura

Brief Summary: The following study is being conducted to explore the safety and effectiveness of a new chemical entity called NXN-188 in subjects with a history of migraine with aura. In this study subjects will treat two attacks of migraine with aura during the aura phase - once with placebo and once with NXN-188.

Detailed Summary:

The purpose of this study is to examine a new chemical entity with 5HT agonist activity and an inhibition of the nitric oxide synthase enzyme (NOS) in patients suffering from migraine with aura. Nitric oxide has diverse roles both in normal and pathological processes including the regulation of blood pressure, neurotransmission, and macrophage defense systems. NO is synthesized by three isoforms of the NOS enzyme: neuronal (n), inducible (i) and endothelial (e). Neuronal NOS (nNOS) is found mainly in neuronal tissue and regulates changes in response sensitivity and cellular plasticity; iNOS is found in macrophages and other tissue, produces NO in response to stress and injury and is one source of inflammation; eNOS is found in endothelial cells, responsible for vascular homeostasis and the presumed mechanism for the effects of nitroglycerine therapy in angina; nitroglycerine is an NO donor. NXN-188 is selectively inhibits nNOS.

There is ample scientific and clinical evidence that NO is involved in the pathogenesis of migraine pain, as well as other pain states characterized by central sensitization (e.g., neuropathic pain). NO donors such as trinitroglycerine induce headache followed by migraine in migraineurs with or without aura ; moreover, platelet nitrates (a signal for increased NO) increase before and during a migraine attack. In addition, increasing NO levels can enhance pain responses in animals, including allodynia in rats; NO is a component of several pathways where pain systems converge in the PNS and CNS and regulates the activity of numerous transmitter systems ; NO is involved in central sensitization particularly those involving NMDA and calcium channels and thought to be a major component of the formation of neuropathic pain states Non-specific NOS inhibitors have been reported to relieve migraine and chronic tension type headaches in human studies. In ani
Sponsor: Danish Headache Center

Current Primary Outcome:

  • The severity of headache measured with a 4 point scale (The Headache Severity Score (HSS)) [ Time Frame: 2 hours after dosing ]
  • Absence of headache [ Time Frame: 2 hours after dosing ]


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • The occurence of any type(s) of adverse events(s) [ Time Frame: 0-48 hours after dosing ]
  • The severity of headache measured with a 4 point scale (The Headache Severity Score (HSS)) [ Time Frame: 0, 1, 2, 4, 8 and 24 hours after dosing ]
  • Clinical Disability measured on a 4 point scale [ Time Frame: 0, 1, 2, 4, 8 and 24 hours after dosing ]
  • Overall evaluation of the study medication [ Time Frame: 24 hours after dosing ]


Original Secondary Outcome: Same as current

Information By: Danish Headache Center

Dates:
Date Received: April 7, 2009
Date Started: May 2009
Date Completion: December 2010
Last Updated: July 27, 2009
Last Verified: July 2009