Calcitonin Gene-related Peptide Levels in Chronic Migraine

Cady, Roger, M.D.

Status and phase: Completed; Phase 4

Conditions: Chronic Migraine

Treatments: Drug: Saline; Drug: OnabotulinumtoxinA

Study type: Interventional

Funder types: Industry

Identifiers

NCT01071096

10-001AL

Details and patient eligibility

About

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 .

Full description

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.

Enrollment: 20 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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20 participants in 2 patient groups, including a placebo group

OnabotulinumtoxinA

Active Comparator group

Description:

Minimum dose of 155 international units (U) OnabotulinumtoxinA Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven specific head/neck muscle areas.

Treatment:

Drug: OnabotulinumtoxinA

Saline

Placebo Comparator group

Description:

155 U Saline administered at 31 fixed-site, fixed-dose injections across seven specific head/neck muscle areas.

Treatment:

Drug: Saline