MigrainePhase 4NCT00753311
Rizatriptan in Acute Treatment of Migraine in Patients With Unilateral Trigeminal-autonomic Symptoms.
A Phase 4 study of Migraine, run by IRCCS San Raffaele at 1 site in Italy.
Trial summary
Triptans are first choice drugs in the acute treatment of migraine and cluster headache. However, while in cluster headache the response rate to subcutaneous sumatriptan is 96%, around 30% of patients fail to respond to a particular triptan. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Migraine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteItaly
- Study dates
- Jul 2009to Oct 2011
- Phase
- Phase 4
- 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 ≥18 years of age at screening. History of migraine with or without aura > 1 year with ≥1 and ≤8 moderate or Severe migraine attacks per month in the 2 months prior to screening that typically last longer than 2 hours.During the migraine attack (if untreated) patient has every time at least 1 of the following symptoms due to the activation of the trigeminal-autonomic reflex (UAs): unilateral conjunctival injection and/or lacrimation and/or nasal congestion/rhinorrhea and/or ptosis and/or eyelid oedema and/or forehead/facial sweating. A patient who is of reproductive potential agrees to remain abstinent or use (or have their partner use) 2 acceptable methods of birth control within the projected duration of the study (intrauterine device (IUD),diaphragm with spermicide,contraceptive sponge,condoms,vasectomy.Health condition in the opinion of the investigator based on screening assessment including medical history,physical examination,and laboratory testing carried out within ~2 months prior to study treatment.Patient agrees to participate by giving written informed consent and able to complete the study questionnaire(s)and paper diary.
Who cannot join
- Patient is pregnant or breast-feeding, or expecting to conceive within the projected duration of the study.Patient has difficulty distinguishing his/her migraine attacks from tension or interval headaches.History of predominantly mild migraine attacks or migraines usually resolved spontaneously in less than 2 hours.Basilar or hemiplegic migraine headache.Patient has more than 15 headache-days per month or has taken medication for acute headache on more than 10 days per month in any of the 3 months prior to screening.Patient is taking migraine Propranolol or has discontinued it from less than 14 days.Patient is taking migraine prophylactic medication where the prescribed daily dose has changed during the 3 months prior to screening.Patient was > 50 years old at age of migraine onset. Recent history (within the past 5 years) or current evidence of drug or alcohol abuse or is a "recreational user" of illicit drugs.Concomitant use of propranolol, ergot derivatives, methysergide or MAO inhibitors.Hypersensitivity to any marketed 5HT1B/1D receptor agonist.History or clinical evidence of ischemic heart disease (e.g., angina pectoris of any type, history of myocardial infarction or documented silent ischemia) or symptoms or findings consistent with ischemic heart disease, coronary artery vasospasm (including Prinzmetal's variant angina,or other significant underlying cardiovascular disease.Patient has clinical,laboratory,or ECG evidence of uncontrolled hypertension, uncontrolled diabetes, or significant pulmonary, renal, hepatic, endocrine, or other systemic disease in the opinion of the investigator.Patient has, in the opinion of the investigator, other confounding pain syndromes, psychiatric conditions such as uncontrolled major depression based on criteria such as DSM-IV, dementia or significant neurological disorders other than migraine.History of neoplastic disease ≤ 5 years prior to signing informed consent.Patient has a history of gastric or small intestinal surgery (including gastric bypass surgery or banding), or has a disease that causes malabsorption. History or current evidence of any clinically significant disease that according to the investigator might confound the results of the study, complicate the interpretation of the study results, interfere with the patient's participation for the full duration of the study, or pose an additional undue risk to the patient.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Double Blind, Controlled Versus Placebo in Parallel Groups, Study to Evaluate the Efficacy of 10 mg Lyophilized Oral Rizatriptan in the Acute Treatment of Migraine in Patients With Unilateral Trigeminal Autonomic Symptoms.
Triptans are first choice drugs in the acute treatment of migraine and cluster headache. However, while in cluster headache the response rate to subcutaneous sumatriptan is 96%, around 30% of patients fail to respond to a particular triptan. Nonresponse is likely to be due to a variety of factors, including low and inconsistent absorption, inadequate dosing, and variability in individual response5. Timing of administration is also a crucial issue. In fact, an early treatment of the attack, when the pain is still mild, may increase the responders rate by circumventing the development of cutaneous allodynia (expression of central sensitization of pain pathway) during the course of the attack.
Several studies have been performed in an attempt to genetically, psychologically and clinically characterize the triptan responders but failed to provide conclusive results.
Read more
Nevertheless, we suggested that the presence of UAs during the migraine attack might predict a good response to triptans. UAs are common in migraine patients. They have been reported in almost one out of two migraineurs (45.8%) attending a tertiary headache centre and in more than one out of four (26.9%) in a population-based study. In an open study with sumatriptan 50 mg performed on 72 migraine patients with UAs, we described pain relief in 65.3% of the patients at 1 h and in 81.9% at 2 h, while pain-free in 30.6% at 1 h and in 61.1% at 2 h. We hypothesized a large-scale recruitment of peripheral neurovascular 5-HT1B/1D receptors consequent to the activation of the trigeminal-autonomic reflex in such patients. Our hypothesis has received further confirmation by the demonstration of higher levels of calcitonin gene-related peptide, neurokinin A and vasoactive intestinal peptide (the hallmark of the activation of the trigeminal autonomic reflex) in external jugular blood in rizatriptan responders than in non-responders.
The investigators therefore postulate that migraineurs with UAs may respond better to rizatriptan than "general" migraine population.
The aim of the study is to evaluate the efficacy of rizatriptan 10 mg lyophilized wafer (MLT) compared to placebo in the treatment of acute migraine in patients with unilateral autonomic symptoms (UAs: unilateral lacrimation, eye redness, eyelid oedema, nasal congestion or rhinorrhoea, miosis or ptosis, forehead or facial sweating) during the migraine attack.
Read the detailed description
We tested the hypothesis that the presence of unilateral cranial autonomic symptoms in migraine predicts a good response to triptans. In this randomized, double-blind, placebo-controlled study 80 migraineurs with unilateral cranial autonomic symptoms were assigned to rizatriptan 10 mg wafer or placebo (ratio 1:1) and treated for a single moderate or severe migraine attack. The primary endpoints were pain freedom at 2 h and total migraine freedom at 2 h. Secondary endpoints included pain relief, no associated symptoms and sustained pain freedom or relief. Significantly more patients reported pain freedom at 2 h after taking rizatriptan than after placebo (54% vs 8%; p<0.001). Similarly, significantly more patients reported total migraine freedom at 2 h after rizatriptan than after placebo (51% vs 8%; p<0.001). Rizatriptan was also more effective than placebo on most secondary endpoints. Migraineurs with unilateral cranial autonomic symptoms respond better than the general migraine population to rizatriptan, probably owing to intense trigeminal peripheral afferent activation which strongly recruits peripheral neurovascular 5-HT1B/1D receptors. Acute and preventive pharmacological trials in migraine should focus also on this subset of migraine patients.
- Conditions
- Migraine
- Being tested
- rizatriptan or placebo
- Keywords
- migraine, rizatriptan, unilateral trigeminal autonomic symptoms, Migraine with or without aura
- Medical subject headings
- Migraine Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rizatriptan or placeboDrug
Patient took 1 rizatriptan 10 mg wafer or placebo as soon as their migraine headache became of moderate or severe intensity.
| Study group | Role | What they receive |
|---|---|---|
| Rizatriptan | Active comparator | Patients with migraine with and without aura will be enrolled and randomly provided with study drug (rizatriptan 10 mg MLT or placebo, ratio 1:1). Patients were encouraged to take migraine medication as soon as their migraine headache became moderate or severe. If the moderate or severe migraine headache persisted 2 h after dosing, or recurred within 24 h, patients had the option of taking their own rescue medication but triptans and ergot derivatives were prohibited for 24 h after study medication intake. Receives: Drug: rizatriptan or placebo |
| placebo | Placebo comparator | Patients who met all the study entry criteria were enrolled and randomly allocated to receive either rizatriptan 10 mg wafer or placebo (ratio 1:1).Patients were encouraged to take migraine medication as soon as their migraine headache became moderate or severe. If the moderate or severe migraine headache persisted 2 h after dosing, or recurred within 24 h, patients had the option of taking their own rescue medication but triptans and ergot derivatives were prohibited for 24 h after study medication intake. Receives: Drug: rizatriptan or placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rating of headache severity at baseline and 2 hours postdose.
Measured: 12 months
Secondary outcomes (1)
Rating of headache severity, associated symptoms and disability at 0.5, 1, 1.5, 2, 3, 4, and 24 hours post dose. b.Headache recurrence. c.Use of rescue medication.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2008 (estimated)
- Study startJul 2009
- Primary completionNov 2010
- Study completionOct 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MigraineStudies of the same condition, open and under way.
- More trials run by IRCCS San RaffaeleThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- IRCCS San Raffaele
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Principal investigator, Piero Barbanti, MD, IRCCS San Raffaele
- Investigators
- Piero Barbanti, MD, PhD, Principal investigator, IRCCS San Raffaele
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00753311
- Sponsor's protocol ID
- 50/07ssr-msd01-3407
- Status last verified
- Oct 2011
- First submitted
- 15 Sep 2008
- Last updated
- 12 Oct 2011
- Results posted
- No
- Data monitoring committee
- No
Publications
Barbanti P, Fofi L, Dall'Armi V, Aurilia C, Egeo G, Vanacore N, Bonassi S. Rizatriptan in migraineurs with unilateral cranial autonomic symptoms: a double-blind trial. J Headache Pain. 2012 Jul;13(5):407-14. doi: 10.1007/s10194-012-0440-y. Epub 2012 Mar 30.
PubMed 22460943
Study at a glance
From the registry record, last updated by the sponsor on 12 Oct 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double Blind, Controlled Versus Placebo in Parallel Groups, Study to Evaluate the Efficacy of 10 mg Lyophilized Oral Rizatriptan in the Acute Treatment of Migraine in Patients With Unilateral Trigeminal Autonomic Symptoms.
- ClinicalTrials.gov ID
- NCT00753311
- Acronym / sponsor ID
- 50/07ssr-msd01-3407
- Conditions
- Migraine
- Keywords
- migraine, rizatriptan, unilateral trigeminal autonomic symptoms, Migraine with or without aura
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- IRCCS San RaffaeleUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- Jul 2009
- Primary completion
- Nov 2010 (actual)
- Study completion
- Oct 2011 (actual)
- First posted
- 16 Sep 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Triptans are first choice drugs in the acute treatment of migraine and cluster headache. However, while in cluster headache the response rate to subcutaneous sumatriptan is 96%, around 30% of patients fail to respond to a particular triptan. Nonresponse is likely to be due to a variety of factors, including low and inconsistent absorption, inadequate dosing, and variability in individual response5. Timing of administration is also a crucial issue. In fact, an early treatment of the attack, when the pain is still mild, may increase the responders rate by circumventing the development of cutaneous allodynia (expression of central sensitization of pain pathway) during the course of the attack.
Several studies have been performed in an attempt to genetically, psychologically and clinically characterize the triptan responders but failed to provide conclusive results.
Nevertheless, we suggested that the presence of UAs during the migraine attack might predict a good response to triptans. UAs are common in migraine patients. They have been reported in almost one out of two migraineurs (45.8%) attending a tertiary headache centre and in more than one out of four (26.9%) in a population-based study. In an open study with sumatriptan 50 mg performed on 72 migraine patients with UAs, we described pain relief in 65.3% of the patients at 1 h and in 81.9% at 2 h, while pain-free in 30.6% at 1 h and in 61.1% at 2 h. We hypothesized a large-scale recruitment of peripheral neurovascular 5-HT1B/1D receptors consequent to the activation of the trigeminal-autonomic reflex in such patients. Our hypothesis has received further confirmation by the demonstration of higher levels of calcitonin gene-related peptide, neurokinin A and vasoactive intestinal peptide (the hallmark of the activation of the trigeminal autonomic reflex) in external jugular blood in rizatriptan responders than in non-responders.
The investigators therefore postulate that migraineurs with UAs may respond better to rizatriptan than "general" migraine population.
The aim of the study is to evaluate the efficacy of rizatriptan 10 mg lyophilized wafer (MLT) compared to placebo in the treatment of acute migraine in patients with unilateral autonomic symptoms (UAs: unilateral lacrimation, eye redness, eyelid oedema, nasal congestion or rhinorrhoea, miosis or ptosis, forehead or facial sweating) during the migraine attack.
Detailed description
We tested the hypothesis that the presence of unilateral cranial autonomic symptoms in migraine predicts a good response to triptans. In this randomized, double-blind, placebo-controlled study 80 migraineurs with unilateral cranial autonomic symptoms were assigned to rizatriptan 10 mg wafer or placebo (ratio 1:1) and treated for a single moderate or severe migraine attack. The primary endpoints were pain freedom at 2 h and total migraine freedom at 2 h. Secondary endpoints included pain relief, no associated symptoms and sustained pain freedom or relief. Significantly more patients reported pain freedom at 2 h after taking rizatriptan than after placebo (54% vs 8%; p<0.001). Similarly, significantly more patients reported total migraine freedom at 2 h after rizatriptan than after placebo (51% vs 8%; p<0.001). Rizatriptan was also more effective than placebo on most secondary endpoints. Migraineurs with unilateral cranial autonomic symptoms respond better than the general migraine population to rizatriptan, probably owing to intense trigeminal peripheral afferent activation which strongly recruits peripheral neurovascular 5-HT1B/1D receptors. Acute and preventive pharmacological trials in migraine should focus also on this subset of migraine patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Rizatriptan | Active comparator | Drug: rizatriptan or placeboPatients with migraine with and without aura will be enrolled and randomly provided with study drug (rizatriptan 10 mg MLT or placebo, ratio 1:1). Patients were encouraged to take migraine medication as soon as their migraine headache became moderate or severe. If the moderate or severe migraine headache persisted 2 h after dosing, or recurred within 24 h, patients had the option of taking their own rescue medication but triptans and ergot derivatives were prohibited for 24 h after study medication intake. |
| placebo | Placebo comparator | Drug: rizatriptan or placeboPatients who met all the study entry criteria were enrolled and randomly allocated to receive either rizatriptan 10 mg wafer or placebo (ratio 1:1).Patients were encouraged to take migraine medication as soon as their migraine headache became moderate or severe. If the moderate or severe migraine headache persisted 2 h after dosing, or recurred within 24 h, patients had the option of taking their own rescue medication but triptans and ergot derivatives were prohibited for 24 h after study medication intake. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Male or female ≥18 years of age at screening. History of migraine with or without aura > 1 year with ≥1 and ≤8 moderate or Severe migraine attacks per month in the 2 months prior to screening that typically last longer than 2 hours.During the migraine attack (if untreated) patient has every time at least 1 of the following symptoms due to the activation of the trigeminal-autonomic reflex (UAs): unilateral conjunctival injection and/or lacrimation and/or nasal congestion/rhinorrhea and/or ptosis and/or eyelid oedema and/or forehead/facial sweating. A patient who is of reproductive potential agrees to remain abstinent or use (or have their partner use) 2 acceptable methods of birth control within the projected duration of the study (intrauterine device (IUD),diaphragm with spermicide,contraceptive sponge,condoms,vasectomy.Health condition in the opinion of the investigator based on screening assessment including medical history,physical examination,and laboratory testing carried out within ~2 months prior to study treatment.Patient agrees to participate by giving written informed consent and able to complete the study questionnaire(s)and paper diary.
Key exclusion criteria (1 listed)
- Patient is pregnant or breast-feeding, or expecting to conceive within the projected duration of the study.Patient has difficulty distinguishing his/her migraine attacks from tension or interval headaches.History of predominantly mild migraine attacks or migraines usually resolved spontaneously in less than 2 hours.Basilar or hemiplegic migraine headache.Patient has more than 15 headache-days per month or has taken medication for acute headache on more than 10 days per month in any of the 3 months prior to screening.Patient is taking migraine Propranolol or has discontinued it from less than 14 days.Patient is taking migraine prophylactic medication where the prescribed daily dose has changed during the 3 months prior to screening.Patient was > 50 years old at age of migraine onset. Recent history (within the past 5 years) or current evidence of drug or alcohol abuse or is a "recreational user" of illicit drugs.Concomitant use of propranolol, ergot derivatives, methysergide or MAO inhibitors.Hypersensitivity to any marketed 5HT1B/1D receptor agonist.History or clinical evidence of ischemic heart disease (e.g., angina pectoris of any type, history of myocardial infarction or documented silent ischemia) or symptoms or findings consistent with ischemic heart disease, coronary artery vasospasm (including Prinzmetal's variant angina,or other significant underlying cardiovascular disease.Patient has clinical,laboratory,or ECG evidence of uncontrolled hypertension, uncontrolled diabetes, or significant pulmonary, renal, hepatic, endocrine, or other systemic disease in the opinion of the investigator.Patient has, in the opinion of the investigator, other confounding pain syndromes, psychiatric conditions such as uncontrolled major depression based on criteria such as DSM-IV, dementia or significant neurological disorders other than migraine.History of neoplastic disease ≤ 5 years prior to signing informed consent.Patient has a history of gastric or small intestinal surgery (including gastric bypass surgery or banding), or has a disease that causes malabsorption. History or current evidence of any clinically significant disease that according to the investigator might confound the results of the study, complicate the interpretation of the study results, interfere with the patient's participation for the full duration of the study, or pose an additional undue risk to the patient.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| rizatriptan or placeboPatient took 1 rizatriptan 10 mg wafer or placebo as soon as their migraine headache became of moderate or severe intensity. | Drug | Rizatriptan, placebo |
Primary outcome
Rating of headache severity at baseline and 2 hours postdose.
Time frame: 12 months
1 secondary outcome
Rating of headache severity, associated symptoms and disability at 0.5, 1, 1.5, 2, 3, 4, and 24 hours post dose. b.Headache recurrence. c.Use of rescue medication.
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2011.
- Derived from this study: PubMed 22460943Barbanti P, Fofi L, Dall'Armi V, Aurilia C, Egeo G, Vanacore N, Bonassi S. Rizatriptan in migraineurs with unilateral cranial autonomic symptoms: a double-blind trial. J Headache Pain. 2012 Jul;13(5):407-14. doi: 10.1007/s10194-012-0440-y. Epub 2012 Mar 30.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Piero Barbanti, MD, PhD principal investigator
IRCCS San Raffaele
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study of Migraine, run by IRCCS San Raffaele at 1 site in Italy.
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 1 inclusion and 1 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: finished, as of the sponsor's last update on 12 Oct 2011. 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 Italy. 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. Some participants in this study may receive a placebo. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rating of headache severity at baseline and 2 hours postdose. (time frame: 12 months). 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 NCT00753311, which also lists 1 linked publication.
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 12 Oct 2011.