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Migraine With AuraPhase 2NCT00877838

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

A Phase 2 study testing NXN-188 in people with Migraine With Aura, run by Danish Headache Center at 1 site in Denmark.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Migraine With Aura
What is being tested?
NXN-188
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
40 participants
Where
1 siteDenmark
Study dates
May 2009to Dec 2010
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female migraineurs with aura between 18 and 65 years old, inclusive
  • Meets the following criteria for migraine headache with aura:
  • Diagnosed with a history of migraine with aura
  • Aura consisting of at least one of the following, but no muscle weakness or paralysis:
  • Fully reversible visual symptoms (e.g. flickering lights, spots, lines, loss of vision)
  • Fully reversible sensory symptoms (e.g. pins and needles, numbness)
Show all 25Show fewer
  • Fully reversible dysphasia (speech disturbance)
  • Aura has at least two of the following characteristics:
  • Visual symptoms affecting just one side of the field of vision and/or sensory symptoms affecting just one side of the body
  • At least one aura symptom develops gradually over more than 5 minutes and/or different aura symptoms occur one after the other over more than 5 minutes
  • Each symptom lasts from 5-60 minutes
  • At least one migraine headache with aura every 8-weeks and resulting in moderate to severe pain (on a 4-point categorical scale) within 2 hours of the onset of aura.
  • Migraine pain following aura in at least 75% of occurrences
  • The subject has a body mass index (BMI) within the range of 18 to 32
  • The subject is in general good health as determined by the medical history, physical exam, clinical laboratory tests, vital signs [heart rate (HR) and blood pressure (BP; after a 3-minute sitting period)] and ECG
  • ALT cannot be above 1.5x upper limit of normal; creatinine and urea must be within normal limits
  • The subject must be able to speak, read, and understand Danish sufficiently to understand the nature of the study, to provide written informed consent, and complete all study assessments
  • The subject is willing and able to comply with all testing requirements defined in the protocol
  • All females will avoid pregnancy at least 10 days before Visit 1, during the study and up until 3 months after Visit 2
  • Women of childbearing potential must be using a reliable form of contraception. A reliable form of contraception is defined as follows:
  • sterilisation (via hysterectomy or bilateral tubal ligation)
  • sterilisation of partner
  • IUD,
  • birth control pills on stable dose for at least three months before Visit 1, and one month after visit 2.
  • Medroxyprogesterone acetate (Depo-Provera) or etonogestrel (implanon) active for at least three months prior to the study and with continued administration at intervals sufficient to maintain contraceptive efficacy throughout the study period and at least one month after visit 2. Males must use condoms as contraception.

Who cannot join

  • Presence of any clinically significant condition that would preclude study participation, as evaluated by the investigator
  • Are pregnant or lactating
  • History of significant neurological, hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary, rheumatologic, autoimmune, or metabolic disease
  • Receiving any medication that, in the opinion of the Investigator or designee, may pose a risk of compromising tolerance or compliance
  • Are known to or suspected to be currently abusing alcohol or drugs, or have a history (within the past 12 months) of active alcohol or drug abuse
  • Participation in another drug or biologic study within 30 days preceding randomization into this study or during participation in this study
  • Subjects who are unable or unwilling, in the opinion of the Investigator, to comply with all study procedures and cooperate fully with study center staff

Trial locations and contacts

1 site in 1 country.

Peer Tfelt-Hansen, MD, Dr Med Sci contact

+4543 23 27 14

andhou05@glo.regionh.dk

Denmark1 site, 1 recruiting

  • Danish Headache Center

    Glostrup Municipality, 2600

    Anne Werner Hauge, MD, ahauge@dadlnet.dk

    Anders Hougaard, andhou05@glo.regionh.dk

    Recruiting

Other trials in Denmark

About this study

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

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.

Read the detailed description

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 animals, NOS inhibitors reduce pain-related behaviors in multiple neuropathic pain models and spinal cord ischemia as well as reducing pain related behaviors in chemically-induced pain models, particularly in secondary pain states.

The development of central sensitization in the course of a migraine attack suggests a role for the neuronal isoform of the NOS enzyme.

NXN-188 can bind to both 5-HT1D and 5-HT1B receptors with potency similar to sumatriptan; it also selectively binds to nNOS with a level of nNOS inhibition similar to L-NMMA. NXN-188 is devoid of any relevant eNOS inhibition in in vitro cloned human enzyme assays or ex vivo in human coronary arteries and is expected to be effective in treating migraine by inhibition of the nNOS enzyme without vasoconstrictive effects associated with non-selective compounds such as L-NMMA.

The following study is being conducted to further explore NXN-188 response in subjects with a migraine history of 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.

Being tested
NXN-188, Placebo
Keywords
Headache, Migraine, Aura, Acute, Attack, Clinical, Trial, Intervention, Nitrogen Oxide, NOS, nNOS, Triptan, 5HT, Serotonin
Medical subject headings
Migraine with Aura, Headache, Migraine Disorders, Epilepsy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NXN-188Drug

    NXN-188 600 mg (3 gelatin capsules each containing 200 mg) when experiencing migraine aura.

  • PlaceboDrug

    Gelatin capsules resembling the ones containing the active substance

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The severity of headache measured with a 4 point scale (The Headache Severity Score (HSS))

    Measured: 2 hours after dosing

  2. Absence of headache

    Measured: 2 hours after dosing

Secondary outcomes (4)

  1. The occurence of any type(s) of adverse events(s)

    Measured: 0-48 hours after dosing

  2. The severity of headache measured with a 4 point scale (The Headache Severity Score (HSS))

    Measured: 0, 1, 2, 4, 8 and 24 hours after dosing

  3. Clinical Disability measured on a 4 point scale

    Measured: 0, 1, 2, 4, 8 and 24 hours after dosing

  4. Overall evaluation of the study medication

    Measured: 24 hours after dosing

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Apr 2009 (estimated)
  2. Study startMay 2009
  3. Primary completionMar 2010 (estimated)
  4. Study completionDec 2010 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
40 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00877838
Sponsor's protocol ID
NXN-188-202
Status last verified
Jul 2009
First submitted
7 Apr 2009
Last updated
28 Jul 2009
Results posted
No
Data monitoring committee
Yes

Publications

  • Lassen LH, Christiansen I, Iversen HK, Jansen-Olesen I, Olesen J. The effect of nitric oxide synthase inhibition on histamine induced headache and arterial dilatation in migraineurs. Cephalalgia. 2003 Nov;23(9):877-86. doi: 10.1046/j.1468-2982.2003.00586.x.

    PubMed 14616929

  • Afridi S, Kaube H, Goadsby PJ. Occipital activation in glyceryl trinitrate induced migraine with visual aura. J Neurol Neurosurg Psychiatry. 2005 Aug;76(8):1158-60. doi: 10.1136/jnnp.2004.050633.

    PubMed 16024898

  • Alderton WK, Cooper CE, Knowles RG. Nitric oxide synthases: structure, function and inhibition. Biochem J. 2001 Aug 1;357(Pt 3):593-615. doi: 10.1042/0264-6021:3570593.

    PubMed 11463332

  • Burstein R, Collins B, Jakubowski M. Defeating migraine pain with triptans: a race against the development of cutaneous allodynia. Ann Neurol. 2004 Jan;55(1):19-26. doi: 10.1002/ana.10786.

    PubMed 14705108

  • Costa A, Smeraldi A, Tassorelli C, Greco R, Nappi G. Effects of acute and chronic restraint stress on nitroglycerin-induced hyperalgesia in rats. Neurosci Lett. 2005 Jul 22-29;383(1-2):7-11. doi: 10.1016/j.neulet.2005.03.026. Epub 2005 Apr 18.

    PubMed 15936504

  • Handy RL, Moore PK. Effects of selective inhibitors of neuronal nitric oxide synthase on carrageenan-induced mechanical and thermal hyperalgesia. Neuropharmacology. 1998;37(1):37-43. doi: 10.1016/s0028-3908(97)00201-3.

    PubMed 9680257

  • Heinzen EL, Pollack GM. Pharmacodynamics of morphine-induced neuronal nitric oxide production and antinociceptive tolerance development. Brain Res. 2004 Oct 15;1023(2):175-84. doi: 10.1016/j.brainres.2004.07.015.

    PubMed 15374743

  • Inoue T, Mashimo T, Shibata M, Shibuta S, Yoshiya I. Rapid development of nitric oxide-induced hyperalgesia depends on an alternate to the cGMP-mediated pathway in the rat neuropathic pain model. Brain Res. 1998 May 11;792(2):263-70. doi: 10.1016/s0006-8993(98)00147-4.

    PubMed 9593928

  • Levy D, Zochodne DW. NO pain: potential roles of nitric oxide in neuropathic pain. Pain Pract. 2004 Mar;4(1):11-8. doi: 10.1111/j.1533-2500.2004.04002.x.

    PubMed 17129298

  • Martelletti P, D'Alo S, Stirparo G, Rinaldi C, Cifone MG, Giacovazzo M. Modulation of nitric oxide synthase by nitric oxide donor compounds in migraine. Int J Clin Lab Res. 1998;28(2):135-9. doi: 10.1007/s005990050033.

    PubMed 9689557

  • Mungrue IN, Bredt DS, Stewart DJ, Husain M. From molecules to mammals: what's NOS got to do with it? Acta Physiol Scand. 2003 Oct;179(2):123-35. doi: 10.1046/j.1365-201X.2003.01182.x.

    PubMed 14510775

  • Naik AK, Tandan SK, Kumar D, Dudhgaonkar SP. Nitric oxide and its modulators in chronic constriction injury-induced neuropathic pain in rats. Eur J Pharmacol. 2006 Jan 13;530(1-2):59-69. doi: 10.1016/j.ejphar.2005.11.029. Epub 2005 Dec 20.

    PubMed 16364289

  • Osborne MG, Coderre TJ. Effects of intrathecal administration of nitric oxide synthase inhibitors on carrageenan-induced thermal hyperalgesia. Br J Pharmacol. 1999 Apr;126(8):1840-6. doi: 10.1038/sj.bjp.0702508.

    PubMed 10372828

  • Shimomura T, Murakami F, Kotani K, Ikawa S, Kono S. Platelet nitric oxide metabolites in migraine. Cephalalgia. 1999 May;19(4):218-22. doi: 10.1046/j.1468-2982.1999.019004218.x.

    PubMed 10376166

  • Taffi R, Vignini A, Lanciotti C, Luconi R, Nanetti L, Mazzanti L, Provinciali L, Silvestrini M, Bartolini M. Platelet membrane fluidity and peroxynitrite levels in migraine patients during headache-free periods. Cephalalgia. 2005 May;25(5):353-8. doi: 10.1111/j.1468-2982.2004.00863.x.

    PubMed 15839850

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing NXN-188 in people with Migraine With Aura, run by Danish Headache Center at 1 site in Denmark.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 28 Jul 2009. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Peer Tfelt-Hansen, MD, Dr Med Sci (+4543 23 27 14, andhou05@glo.regionh.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The severity of headache measured with a 4 point scale (The Headache Severity Score (HSS)) (time frame: 2 hours after dosing). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00877838, which also lists 19 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jul 2009.

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