calcitonin gene-related peptide levels in chronic migraine

Conditions: Chronic Migraine

Summary: twenty patients will be enrolled in a 2-site, 7-month, double-blind study conducted to evaluate a reduction in headache days and attacks and calcitonin gene-related peptide (cgrp) levels in saliva following treatment with onabotulinumtoxina versus saline. eligible patients will be randomized and receive injections of onabotulinumtoxina or saline at visit 1. following 3 months plus a 1 month wash out, patients will receive cross-over injections at visit 5. patients will return for monthly visits and exit the study at visit 8. patients will collect saliva at monthly intervals and document in a daily headache diary throughout the study .

this double-blind study will evaluate reduction in number of headache days following treatment with onabotulinumtoxina versus saline. additionally, cgrp levels in saliva will be correlated with a reduction in headache attacks. at visit 1, eligible subjects will be randomized 1:1 to receive injections of onabotulinumtoxina or saline in an identical manner. subjects will collect 3 saliva samples during each month of the 7 month study: 1 collection at baseline headache level, 1 collection at onset of headache that is one degree worse than baseline level that will be treated with acute therapy, and 1 collection at 2 hours following treatment. subjects will document headache and headache symptoms in a daily diary and return to the clinic with diary and saliva samples at monthly visits. following 4 months (including a 1 month washout after visit 4), subjects will return at visit 5 and receive cross-over injections. subjects randomized to onabotulinumtoxina at visit 1 will receive injections of saline. subjects randomized to saline at visit 1 will receive injections of onabotulinumtoxina. subjects will document headache and headache symptoms in a daily diary and return to the clinic with diary and saliva samples at monthly visits. at visit 8, 3 months following re-injection at visit 5, subjects will exit the study.

Eligibility criteria:
inclusion criteria: * must be outpatient, male or female, of any race, between 18 and 65 years of age. * if female of childbearing potential must have negative pregnancy test result at screening visit and practice reliable method of contraception. a female is considered of childbearing potential unless she is post menopausal for at least 12 months prior to administration of study drug, without a uterus and/or both ovaries or has been surgically sterilized for at least 6 months prior to study drug administration. reliable methods of contraception are: complete abstinence from intercourse from 2 weeks prior to administration of the investigational product, throughout the study, and for a time interval (5 days) after completion or premature discontinuation from the study; or, history of bilateral tubal ligation; or, sterilization of male partner; or, implants of levonorgestrel; or, injectable progestogen; or, oral contraceptive (combination therapy with ethinyl estradiol plus a progestin) with a placebo week every 1-3 months; or, any intrauterine device (iud) with published data showing that the highest expected failure rate is less than 1% per year (not all iud's meet this criterion) in use at least 30 days prior to study drug administration; or, spermicide plus a mechanical barrier (e.g., spermicide plus a male condom or a female diaphragm); or, any other barrier methods (only is used in combination with any of the above acceptable methods) in use at least 14 days prior to study drug administration; or, any other methods with published data showing that the highest expected failure rate for that methods is less than 1% per year. * must have history of chronic migraine (with or without aura) according to the criteria proposed by the headache classification committee of the international headache society (ihs) for at least 3 months prior to enrollment. * must be able to understand the requirements of the study including maintaining a headache diary, and signing informed consent. * must be in good general health as determined by investigator. * if taking migraine preventive, must be on a stable dose of preventive medication for at least 3 months prior to screening. exclusion criteria: * if female, is pregnant, planning to become pregnant during the study period, is breast feeding, or is of childbearing potential and not practicing a reliable form of birth control. * has headache disorders outside ihs-defined chronic migraine definition. * has evidence of underlying pathology contributing to their headaches. * has any pathology of the salivary glands such as sialadenitis (e.g. sjogren's syndrome, viral or bacterial sialadenitis) or condition or symptom that would alter the content of saliva. * has any medical condition that may increase their risk with exposure to onabotulinumtoxina including diagnosed myasthenia gravis, eaton-lambert syndrome, amyotrophic lateral sclerosis, or any other significant disease that might interfere with neuromuscular function. * has profound atrophy or weakness of muscles in the target areas of injection. * has skin conditions or infections at any of the injection sites. * has allergy or sensitivities to any component of the test medication. * who in the opinion of the investigator, has active major psychiatric or depressive disorders including alcohol/drug abuse. * meets international headache society criteria for medication overuse with opioid or butalbital containing products. * is planning or requiring surgery during the study. * has a history of poor compliance with medical treatment. * is currently participating in an investigational drug study or has participated in an investigational drug study within the previous 30 days of the screening visit.

Keywords: botox onabotulinumtoxina chronic migraine calcitonin gene-related peptide saliva