Calcitonin Gene-related Peptide Levels in Chronic Migraine
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Purpose
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 .
| Condition | Intervention | Phase |
|---|---|---|
|
Chronic Migraine |
Drug: OnabotulinumtoxinA Drug: Saline |
Phase 4 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment |
| Official Title: | Calcitonin Gene-related Peptide (CGRP) Levels in the Pathogenesis of Chronic Migraine |
- Change in Number of Headache Days Per Month From Baseline (BL) to Months 1 Through 7. [ Time Frame: Baseline (collected historically at screening) versus (vs.) Month (Mo) 1, Mo 2, Mo 3, Mo 4, Mo 5, Mo 6, and Mo 7 ] [ Designated as safety issue: No ]Baseline number of headache days per month collected historically at screening. Post-treatment number of headache days collected per month via diary.
- Change in Number of Headache Days Per Month From Baseline to Month 1 (M1), Month 1 to Month 2 (M2), and Month 2 to Month 3 (M3). [ Time Frame: Baseline (collected historically at screening) vs. Mo 1, Mo 1 vs. Mo 2, Mo 2 vs. Mo 3, Mo 3 vs. Mo 4, Mo 4 vs. Mo 5, Mo 5 vs. Mo 6, and Mo 6 vs. Mo 7 ] [ Designated as safety issue: No ]Baseline number of headache days per month collected historically at screening. Post-treatment number of headache days collected per month via diary.
- Inter-ictal (Baseline) Levels of Saliva Calcitonin Gene-related Peptide (CGRP) [ Time Frame: Baseline levels collected for OnabotulinumtoxinA and Saline treatment during Months 1 through 7 ] [ Designated as safety issue: No ]CGRP Level collected each month when subject did not have a headache or was at lowest pain level of headache that month.
- Saliva CGRP Levels for OnabotulinumtoxinA Responders (Reduction of Headache Days Greater Than 30%) vs. Non-responders and Saline [ Time Frame: For OnabotulinumtoxinA and Saline treatment months 1, 2 and 3 ] [ Designated as safety issue: No ]Saliva samples collected at Baseline (at no headache or lowest level of headache), at headache attack directly before taking rescue medication and 2 hours after treating with rescue medication.
- Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders [ Time Frame: For OnabotulinumtoxinA and Saline treatment months 1, 2 and 3 at Baseline level (inter-ictal) and at onset of headache that is one degree worse than Baseline level and that will be treated with acute therapy ] [ Designated as safety issue: No ]Only cytokines with a mean densimetric value 1.65 times the background grey value in a minimum of 3 patients were considered detectable. These are reported below. Values normalized to positive control array spots after background subtraction: C5/C5a, CD40 Ligand, Granulocyte Colony Stimulating Factor (G-CSF), Growth Regulated Oncogene(GRO)-alpha, Soluble Intercellular Adhesion Molecule (sICAM)-1, Interferon gamma (IFN-y), Interleukin(IL)-1alpha, 1beta, 1ra, 8, 16, 17E, & 23, Interferon Gamma-Induced Protein 10 (IP-10), Interferon-inducible T cell alpha chemoattractant (I-TAC), Macrophage Migration Inhibitory Factor (MIF), Serpin E1, and Regulated Upon Activation Normal T-cell Expressed (RANTES)
| Enrollment: | 20 |
| Study Start Date: | June 2010 |
| Study Completion Date: | June 2011 |
| Primary Completion Date: | June 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: OnabotulinumtoxinA
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.
|
Drug: OnabotulinumtoxinA
Minimum dose of 155 U OnabotulinumtoxinA Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven specific head/neck muscle areas. Subjects will continue to monitor headache symptoms with a headache diary and collect saliva samples as instructed. At investigator's discretion, additional 40 U OnabotulinumtoxinA Purified Neurotoxin Complex may be administered unilaterally or bilaterally, using follow-the-pain paradigm. Other Names:
|
|
Placebo Comparator: Saline
155 U Saline administered at 31 fixed-site, fixed-dose injections across seven specific head/neck muscle areas.
|
Drug: Saline
155 U Saline administered at 31 fixed-site, fixed-dose injections across seven specific head/neck muscle areas. Subjects will continue to monitor headache using a headache diary and collect saliva samples as instructed. At investigator's discretion, additional Saline may be administered unilaterally or bilaterally, using follow-the-pain paradigm. Other Name: Placebo
|
Detailed 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.
Eligibility| Ages Eligible for Study: | 18 Years to 65 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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.
Contacts and Locations| United States, Missouri | |
| Clinvest | |
| Springfield, Missouri, United States, 65807 | |
| United States, New York | |
| Island Neurological Associates, P.C. | |
| Plainview, New York, United States, 11803 | |
| Principal Investigator: | Roger K Cady, MD | Clinvest |
More Information
Publications:
| Responsible Party: | Cady, Roger, M.D. |
| ClinicalTrials.gov Identifier: | NCT01071096 History of Changes |
| Other Study ID Numbers: | 10-001AL |
| Study First Received: | February 17, 2010 |
| Results First Received: | January 16, 2012 |
| Last Updated: | February 6, 2013 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by Cady, Roger, M.D.:
|
Botox OnabotulinumtoxinA Chronic Migraine Calcitonin Gene-Related Peptide Saliva |
Additional relevant MeSH terms:
|
Migraine Disorders Headache Disorders, Primary Headache Disorders Brain Diseases Central Nervous System Diseases Nervous System Diseases Calcitonin Gene-Related Peptide Salmon calcitonin Calcitonin Botulinum Toxins, Type A Botulinum Toxins |
Vasodilator Agents Cardiovascular Agents Therapeutic Uses Pharmacologic Actions Bone Density Conservation Agents Physiological Effects of Drugs Neuromuscular Agents Peripheral Nervous System Agents Anti-Dyskinesia Agents Central Nervous System Agents |
ClinicalTrials.gov processed this record on May 22, 2013