Rizatriptan in Acute Treatment of Migraine in Patients With Unilateral Trigeminal-Autonomic Symptoms.

Condition(s) targeted: Migraine

Intervention: Rizatriptan (Drug)

Phase: Phase 4

Status: Not yet recruiting

Sponsored by: IRCCS San Raffaele

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 triptan4. 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 attack6,7.

Several studies have been performed in an attempt to genetically, psychologically and clinically characterize the triptan responders but failed to provide conclusive results8-10.

Nevertheless, we suggested that the presence of UAs during the migraine attack might predict a good response to triptans1,11. 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 study1,3. 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 h11. 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 12.

The investigators therefore postulate that migraineurs with UAs may respond better to rizatriptan than "general" migraine population.

Objectives:

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 attack

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.

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study

Primary outcome: Rating of headache severity at baseline and 2 hours postdose.

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.

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Patient is ≥18 years of age at screening.

- Patient has had a 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 hours13.

- 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)

- Patient is: (a) male or (b) female and not of reproductive potential is eligible

without requiring the use of contraception.

- Patient is judged to be in satisfactory health 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 understands the study procedures and voluntarily agrees to participate by

giving written informed consent.

- Patient is able to complete the study questionnaire(s) and paper diary.

Exclusion Criteria:

- 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.

- Patient has a history of predominantly mild migraine attacks or migraines usually

resolved spontaneously in less than 2 hours.

- Patient has 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.

- Patient has a recent history (within the past 5 years) or current evidence of drug or

alcohol abuse or is a "recreational user" of illicit drugs.

- Patient has a concomitant use of propranolol, ergot derivatives, methysergide or MAO

inhibitors

- Patient has a demonstrated hypersensitivity to any marketed 5HT1B/1D receptor

agonist.

- Patient has a 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.

- Patient has a 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.

- Patient has a 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.

Last updated: September 15, 2008