Chronic Migraine
Conditions
Keywords
Botox, OnabotulinumtoxinA, Chronic Migraine, Calcitonin Gene-Related Peptide, Saliva
Brief 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 .
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.
Interventions
DRUGOnabotulinumtoxinA
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.
DRUGSaline
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.
Sponsors
Allergan
Cady, Roger, M.D.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Number of Headache Days Per Month From Baseline (BL) to Months 1 Through 7. | Baseline (collected historically at screening) versus (vs.) Month (Mo) 1, Mo 2, Mo 3, Mo 4, Mo 5, Mo 6, and Mo 7 | 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). | 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 | Baseline number of headache days per month collected historically at screening. Post-treatment number of headache days collected per month via diary. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Inter-ictal (Baseline) Levels of Saliva Calcitonin Gene-related Peptide (CGRP) | Baseline levels collected for OnabotulinumtoxinA and Saline treatment during Months 1 through 7 | 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 | For OnabotulinumtoxinA and Saline treatment months 1, 2 and 3 | 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 | 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 | 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) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Enrolled Participants Enrolled Participants includes subjects in both Group A (treated with BOTOX and Visit 1 and Placebo at Visit 5) and Group B (treated with Placebo at Visit 1 and BOTOX at Visit 5). | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention (90 Days) | Lost to Follow-up | 1 | 0 |
Baseline characteristics
| Characteristic | Enrolled Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants |
| Age Continuous | 48.45 years STANDARD_DEVIATION 12.87 |
| Region of Enrollment United States | 20 participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 11 / 20 | 15 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 |
Outcome results
Primary
Change in Number of Headache Days Per Month From Baseline (BL) to Months 1 Through 7.
Baseline number of headache days per month collected historically at screening. Post-treatment number of headache days collected per month via diary.
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A | Change in Number of Headache Days Per Month From Baseline (BL) to Months 1 Through 7. | Baseline vs. Month 2 | -9.72 days | Standard Deviation 5.96 |
| Group A | Change in Number of Headache Days Per Month From Baseline (BL) to Months 1 Through 7. | Baseline vs. Month 5 | -8.94 days | Standard Deviation 8.15 |
| Group A | Change in Number of Headache Days Per Month From Baseline (BL) to Months 1 Through 7. | Baseline vs. Month 3 | -10.06 days | Standard Deviation 5.92 |
| Group A | Change in Number of Headache Days Per Month From Baseline (BL) to Months 1 Through 7. | Baseline vs. Month 6 | -9.50 days | Standard Deviation 7.93 |
| Group A | Change in Number of Headache Days Per Month From Baseline (BL) to Months 1 Through 7. | Baseline vs. Month 1 | -7.61 days | Standard Deviation 8.01 |
| Group A | Change in Number of Headache Days Per Month From Baseline (BL) to Months 1 Through 7. | Baseline vs. Month 7 | -6.50 days | Standard Deviation 7.53 |
| Group A | Change in Number of Headache Days Per Month From Baseline (BL) to Months 1 Through 7. | Baseline vs. Month 4 | -9.50 days | Standard Deviation 8.34 |
| Group B | Change in Number of Headache Days Per Month From Baseline (BL) to Months 1 Through 7. | Baseline vs. Month 7 | -4.56 days | Standard Deviation 6.89 |
| Group B | Change in Number of Headache Days Per Month From Baseline (BL) to Months 1 Through 7. | Baseline vs. Month 2 | -5.22 days | Standard Deviation 4.44 |
| Group B | Change in Number of Headache Days Per Month From Baseline (BL) to Months 1 Through 7. | Baseline vs. Month 3 | -5.22 days | Standard Deviation 5.14 |
| Group B | Change in Number of Headache Days Per Month From Baseline (BL) to Months 1 Through 7. | Baseline vs. Month 4 | -6.89 days | Standard Deviation 7.08 |
| Group B | Change in Number of Headache Days Per Month From Baseline (BL) to Months 1 Through 7. | Baseline vs. Month 5 | -6.33 days | Standard Deviation 4.12 |
| Group B | Change in Number of Headache Days Per Month From Baseline (BL) to Months 1 Through 7. | Baseline vs. Month 6 | -9.22 days | Standard Deviation 5.45 |
| Group B | Change in Number of Headache Days Per Month From Baseline (BL) to Months 1 Through 7. | Baseline vs. Month 1 | -6.67 days | Standard Deviation 6.28 |
Primary
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).
Baseline number of headache days per month collected historically at screening. Post-treatment number of headache days collected per month via diary.
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A | 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). | Mo 2 vs. Mo 3 | -0.33 days | Standard Deviation 3.97 |
| Group A | 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). | Mo 4 vs. Mo 5 | 0.56 days | Standard Deviation 3.21 |
| Group A | 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). | Mo 1 vs. Mo 2 | -2.11 days | Standard Deviation 7.2 |
| Group A | 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). | Mo 5 vs. Mo 6 | -0.56 days | Standard Deviation 3.84 |
| Group A | 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). | Mo 3 vs. Mo 4 | 0.56 days | Standard Deviation 3.91 |
| Group A | 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). | Mo 6 vs. M 7 | 3.00 days | Standard Deviation 3.84 |
| Group A | 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). | Baseline vs. Mo 1 | -7.61 days | Standard Deviation 8.01 |
| Group B | 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). | Mo 6 vs. M 7 | 4.67 days | Standard Deviation 5.63 |
| Group B | 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). | Baseline vs. Mo 1 | -6.67 days | Standard Deviation 6.28 |
| Group B | 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). | Mo 1 vs. Mo 2 | 1.44 days | Standard Deviation 7.78 |
| Group B | 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). | Mo 2 vs. Mo 3 | 0.00 days | Standard Deviation 1.94 |
| Group B | 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). | Mo 3 vs. Mo 4 | -1.67 days | Standard Deviation 5.66 |
| Group B | 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). | Mo 4 vs. Mo 5 | 0.56 days | Standard Deviation 4.61 |
| Group B | 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). | Mo 5 vs. Mo 6 | -2.89 days | Standard Deviation 5.42 |
Secondary
Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders
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)
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
Population: Number of Participants Analyzed is low due to some unusable samples and missing samples making comparison between months impossible. 5 Responders and 5 Non-Responders provided enough samples at all time points for comparisons.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | sICAM-1 | 2.60 Florescent Units (FU) | Standard Deviation 2.32 |
| Group A | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IL-23 | 2.45 Florescent Units (FU) | Standard Deviation 1.85 |
| Group A | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IL-17E | 0.86 Florescent Units (FU) | Standard Deviation 0.5 |
| Group A | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IL-16 | 0.91 Florescent Units (FU) | Standard Deviation 0.63 |
| Group A | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IL-1beta | 1.63 Florescent Units (FU) | Standard Deviation 0.8 |
| Group A | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IL-1alpha | 2.30 Florescent Units (FU) | Standard Deviation 1.86 |
| Group A | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | GROa | 1.34 Florescent Units (FU) | Standard Deviation 1.56 |
| Group A | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | G-CSF | 0.92 Florescent Units (FU) | Standard Deviation 0.45 |
| Group A | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | CD40 Ligand | 1.09 Florescent Units (FU) | Standard Deviation 0.25 |
| Group A | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | C5/C5a | 1.38 Florescent Units (FU) | Standard Deviation 0.23 |
| Group A | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IL-1ra | 1.13 Florescent Units (FU) | Standard Deviation 0.56 |
| Group A | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IFN-y | 1.29 Florescent Units (FU) | Standard Deviation 0.34 |
| Group A | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | RANTES | 0.95 Florescent Units (FU) | Standard Deviation 0.41 |
| Group A | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | MIF | 3.71 Florescent Units (FU) | Standard Deviation 6.25 |
| Group A | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | I-TAC | 1.40 Florescent Units (FU) | Standard Deviation 0.78 |
| Group A | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | Serpin E1 | 0.98 Florescent Units (FU) | Standard Deviation 0.17 |
| Group A | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IP-10 | 1.32 Florescent Units (FU) | Standard Deviation 1.05 |
| Group A | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IL-8 | 1.61 Florescent Units (FU) | Standard Deviation 0.83 |
| Group B | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IL-1alpha | 2.88 Florescent Units (FU) | Standard Deviation 4.29 |
| Group B | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IL-1beta | 1.12 Florescent Units (FU) | Standard Deviation 1.09 |
| Group B | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IL-1ra | 2.02 Florescent Units (FU) | Standard Deviation 2.66 |
| Group B | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IL-8 | 1.70 Florescent Units (FU) | Standard Deviation 2.03 |
| Group B | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IL-16 | 2.07 Florescent Units (FU) | Standard Deviation 1.63 |
| Group B | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IL-17E | 1.02 Florescent Units (FU) | Standard Deviation 0.91 |
| Group B | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IL-23 | 1.80 Florescent Units (FU) | Standard Deviation 1.55 |
| Group B | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IP-10 | 0.95 Florescent Units (FU) | Standard Deviation 0.17 |
| Group B | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | I-TAC | 0.28 Florescent Units (FU) | Standard Deviation 0.12 |
| Group B | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | MIF | 9.55 Florescent Units (FU) | Standard Deviation 19.47 |
| Group B | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | Serpin E1 | 0.70 Florescent Units (FU) | Standard Deviation 0.53 |
| Group B | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | RANTES | 0.77 Florescent Units (FU) | Standard Deviation 0.28 |
| Group B | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | C5/C5a | 1.01 Florescent Units (FU) | Standard Deviation 0.9 |
| Group B | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | CD40 Ligand | 1.26 Florescent Units (FU) | Standard Deviation 0.99 |
| Group B | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | G-CSF | 0.93 Florescent Units (FU) | Standard Deviation 0.55 |
| Group B | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | GROa | 3.18 Florescent Units (FU) | Standard Deviation 2.2 |
| Group B | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | sICAM-1 | 0.61 Florescent Units (FU) | Standard Deviation 0.54 |
| Group B | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IFN-y | 0.80 Florescent Units (FU) | Standard Deviation 0.69 |
| Saline | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | C5/C5a | 1.39 Florescent Units (FU) | Standard Deviation 0.8 |
| Saline | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | GROa | 1.40 Florescent Units (FU) | Standard Deviation 1.33 |
| Saline | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | sICAM-1 | 5.99 Florescent Units (FU) | Standard Deviation 6.13 |
| Saline | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | CD40 Ligand | 0.98 Florescent Units (FU) | Standard Deviation 0.37 |
| Saline | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IL-1beta | 1.38 Florescent Units (FU) | Standard Deviation 1.15 |
| Saline | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | I-TAC | 1.01 Florescent Units (FU) | Standard Deviation 0.89 |
| Saline | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | G-CSF | 0.85 Florescent Units (FU) | Standard Deviation 0.24 |
| Saline | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IL-8 | 2.71 Florescent Units (FU) | Standard Deviation 2.29 |
| Saline | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IL-17E | 1.59 Florescent Units (FU) | Standard Deviation 1.79 |
| Saline | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | MIF | 2.71 Florescent Units (FU) | Standard Deviation 4.5 |
| Saline | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IP-10 | 0.86 Florescent Units (FU) | Standard Deviation 0.52 |
| Saline | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | Serpin E1 | 0.70 Florescent Units (FU) | Standard Deviation 0.33 |
| Saline | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IL-1ra | 0.96 Florescent Units (FU) | Standard Deviation 0.39 |
| Saline | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IL-1alpha | 1.50 Florescent Units (FU) | Standard Deviation 0.92 |
| Saline | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | RANTES | 0.93 Florescent Units (FU) | Standard Deviation 0.41 |
| Saline | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IL-23 | 1.06 Florescent Units (FU) | Standard Deviation 0.12 |
| Saline | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IL-16 | 0.75 Florescent Units (FU) | Standard Deviation 0.48 |
| Saline | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IFN-y | 1.29 Florescent Units (FU) | Standard Deviation 0.82 |
| Month 3 vs. Saline Non-Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IL-1alpha | 2.14 Florescent Units (FU) | Standard Deviation 3.04 |
| Month 3 vs. Saline Non-Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | C5/C5a | 1.61 Florescent Units (FU) | Standard Deviation 0.54 |
| Month 3 vs. Saline Non-Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IL-17E | 0.42 Florescent Units (FU) | Standard Deviation 0.13 |
| Month 3 vs. Saline Non-Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IL-16 | 1.97 Florescent Units (FU) | Standard Deviation 1.64 |
| Month 3 vs. Saline Non-Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | MIF | 8.66 Florescent Units (FU) | Standard Deviation 16.79 |
| Month 3 vs. Saline Non-Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IFN-y | 1.92 Florescent Units (FU) | Standard Deviation 2.95 |
| Month 3 vs. Saline Non-Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | sICAM-1 | 2.00 Florescent Units (FU) | Standard Deviation 1.98 |
| Month 3 vs. Saline Non-Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | CD40 Ligand | 1.31 Florescent Units (FU) | Standard Deviation 0.63 |
| Month 3 vs. Saline Non-Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IL-23 | 1.69 Florescent Units (FU) | Standard Deviation 1.54 |
| Month 3 vs. Saline Non-Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IL-8 | 1.22 Florescent Units (FU) | Standard Deviation 1.24 |
| Month 3 vs. Saline Non-Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IL-1beta | 0.51 Florescent Units (FU) | Standard Deviation 0.23 |
| Month 3 vs. Saline Non-Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | GROa | 1.81 Florescent Units (FU) | Standard Deviation 1.32 |
| Month 3 vs. Saline Non-Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | RANTES | 0.91 Florescent Units (FU) | Standard Deviation 0.27 |
| Month 3 vs. Saline Non-Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | G-CSF | 0.99 Florescent Units (FU) | Standard Deviation 0.58 |
| Month 3 vs. Saline Non-Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | I-TAC | 0.94 Florescent Units (FU) | Standard Deviation 0.26 |
| Month 3 vs. Saline Non-Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | Serpin E1 | 0.90 Florescent Units (FU) | Standard Deviation 0.82 |
| Month 3 vs. Saline Non-Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IP-10 | 2.76 Florescent Units (FU) | Standard Deviation 2.23 |
| Month 3 vs. Saline Non-Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IL-1ra | 1.90 Florescent Units (FU) | Standard Deviation 1.58 |
| Month 1 vs. Month 3 Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IP-10 | 1.55 Florescent Units (FU) | Standard Deviation 1.5 |
| Month 1 vs. Month 3 Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IL-23 | 0.93 Florescent Units (FU) | Standard Deviation 0.01 |
| Month 1 vs. Month 3 Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IL-8 | 4.38 Florescent Units (FU) | Standard Deviation 6.98 |
| Month 1 vs. Month 3 Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IL-1ra | 0.88 Florescent Units (FU) | Standard Deviation 0.12 |
| Month 1 vs. Month 3 Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | sICAM-1 | 3.99 Florescent Units (FU) | Standard Deviation 3.22 |
| Month 1 vs. Month 3 Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | I-TAC | 0.67 Florescent Units (FU) | Standard Deviation 0.27 |
| Month 1 vs. Month 3 Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | MIF | 0.80 Florescent Units (FU) | Standard Deviation 0.32 |
| Month 1 vs. Month 3 Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IL-1alpha | 0.86 Florescent Units (FU) | Standard Deviation 0.6 |
| Month 1 vs. Month 3 Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | Serpin E1 | 0.76 Florescent Units (FU) | Standard Deviation 0.39 |
| Month 1 vs. Month 3 Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | RANTES | 1.14 Florescent Units (FU) | Standard Deviation 0.21 |
| Month 1 vs. Month 3 Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | C5/C5a | 1.03 Florescent Units (FU) | Standard Deviation 0.57 |
| Month 1 vs. Month 3 Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IL-1beta | 1.15 Florescent Units (FU) | Standard Deviation 0.12 |
| Month 1 vs. Month 3 Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | CD40 Ligand | 0.91 Florescent Units (FU) | Standard Deviation 0.27 |
| Month 1 vs. Month 3 Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IFN-y | 0.91 Florescent Units (FU) | Standard Deviation 0.34 |
| Month 1 vs. Month 3 Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | G-CSF | 1.07 Florescent Units (FU) | Standard Deviation 0.74 |
| Month 1 vs. Month 3 Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | GROa | 1.05 Florescent Units (FU) | Standard Deviation 0.96 |
| Month 1 vs. Month 3 Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IL-16 | 0.98 Florescent Units (FU) | Standard Deviation 0.66 |
| Month 1 vs. Month 3 Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IL-17E | 1.28 Florescent Units (FU) | Standard Deviation 0.85 |
| Month 1 vs. Month 3 Non-Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | C5/C5a | 3.26 Florescent Units (FU) | Standard Deviation 3.35 |
| Month 1 vs. Month 3 Non-Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IL-1beta | 1.03 Florescent Units (FU) | Standard Deviation 0.43 |
| Month 1 vs. Month 3 Non-Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IL-17E | 1.45 Florescent Units (FU) | Standard Deviation 0.04 |
| Month 1 vs. Month 3 Non-Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | GROa | 0.73 Florescent Units (FU) | Standard Deviation 0.55 |
| Month 1 vs. Month 3 Non-Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IL-8 | 2.28 Florescent Units (FU) | — |
| Month 1 vs. Month 3 Non-Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IL-1alpha | 0.81 Florescent Units (FU) | Standard Deviation 0.32 |
| Month 1 vs. Month 3 Non-Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | RANTES | 1.24 Florescent Units (FU) | Standard Deviation 0.26 |
| Month 1 vs. Month 3 Non-Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | Serpin E1 | 3.16 Florescent Units (FU) | Standard Deviation 3.25 |
| Month 1 vs. Month 3 Non-Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IL-1ra | 1.30 Florescent Units (FU) | Standard Deviation 0.43 |
| Month 1 vs. Month 3 Non-Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IL-16 | 1.10 Florescent Units (FU) | Standard Deviation 0.48 |
| Month 1 vs. Month 3 Non-Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | MIF | 1.24 Florescent Units (FU) | Standard Deviation 0.27 |
| Month 1 vs. Month 3 Non-Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | sICAM-1 | 1.51 Florescent Units (FU) | Standard Deviation 0.15 |
| Month 1 vs. Month 3 Non-Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | I-TAC | 3.65 Florescent Units (FU) | Standard Deviation 1.33 |
| Month 1 vs. Month 3 Non-Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IP-10 | 3.11 Florescent Units (FU) | Standard Deviation 2.69 |
| Month 1 vs. Month 3 Non-Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IL-23 | 2.61 Florescent Units (FU) | Standard Deviation 3.34 |
| Month 1 vs. Month 3 Non-Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | G-CSF | 1.34 Florescent Units (FU) | Standard Deviation 0.76 |
| Month 1 vs. Month 3 Non-Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | CD40 Ligand | 1.22 Florescent Units (FU) | Standard Deviation 0.4 |
| Month 1 vs. Month 3 Non-Responders | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders | IFN-y | 1.63 Florescent Units (FU) | Standard Deviation 0.94 |
Secondary
Inter-ictal (Baseline) Levels of Saliva Calcitonin Gene-related Peptide (CGRP)
CGRP Level collected each month when subject did not have a headache or was at lowest pain level of headache that month.
Time frame: Baseline levels collected for OnabotulinumtoxinA and Saline treatment during Months 1 through 7
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A | Inter-ictal (Baseline) Levels of Saliva Calcitonin Gene-related Peptide (CGRP) | Treatment Month 1 | 39.64 pmol/mg total protein | Standard Error 7.5 |
| Group A | Inter-ictal (Baseline) Levels of Saliva Calcitonin Gene-related Peptide (CGRP) | Treatment Month 2 | 28.37 pmol/mg total protein | Standard Error 7.07 |
| Group A | Inter-ictal (Baseline) Levels of Saliva Calcitonin Gene-related Peptide (CGRP) | Treatment Month 3 | 26.14 pmol/mg total protein | Standard Error 3.93 |
| Group B | Inter-ictal (Baseline) Levels of Saliva Calcitonin Gene-related Peptide (CGRP) | Treatment Month 1 | 40.79 pmol/mg total protein | Standard Error 9.73 |
| Group B | Inter-ictal (Baseline) Levels of Saliva Calcitonin Gene-related Peptide (CGRP) | Treatment Month 2 | 39.14 pmol/mg total protein | Standard Error 9.74 |
| Group B | Inter-ictal (Baseline) Levels of Saliva Calcitonin Gene-related Peptide (CGRP) | Treatment Month 3 | 50.63 pmol/mg total protein | Standard Error 15.04 |
Secondary
Saliva CGRP Levels for OnabotulinumtoxinA Responders (Reduction of Headache Days Greater Than 30%) vs. Non-responders and Saline
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.
Time frame: For OnabotulinumtoxinA and Saline treatment months 1, 2 and 3
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A | Saliva CGRP Levels for OnabotulinumtoxinA Responders (Reduction of Headache Days Greater Than 30%) vs. Non-responders and Saline | Treatment Month 3 - Baseline | 51.33 pmol/mg total protein | Standard Deviation 77.44 |
| Group A | Saliva CGRP Levels for OnabotulinumtoxinA Responders (Reduction of Headache Days Greater Than 30%) vs. Non-responders and Saline | Treatment Month 2 - Baseline | 59.89 pmol/mg total protein | Standard Deviation 49.27 |
| Group A | Saliva CGRP Levels for OnabotulinumtoxinA Responders (Reduction of Headache Days Greater Than 30%) vs. Non-responders and Saline | Treatment Month 1 - Attack | 27.94 pmol/mg total protein | Standard Deviation 21.85 |
| Group A | Saliva CGRP Levels for OnabotulinumtoxinA Responders (Reduction of Headache Days Greater Than 30%) vs. Non-responders and Saline | Treatment Month 2 - 2 Hours Post | 39.13 pmol/mg total protein | Standard Deviation 60.98 |
| Group A | Saliva CGRP Levels for OnabotulinumtoxinA Responders (Reduction of Headache Days Greater Than 30%) vs. Non-responders and Saline | Treatment Month 2 - Attack | 60.14 pmol/mg total protein | Standard Deviation 51.18 |
| Group A | Saliva CGRP Levels for OnabotulinumtoxinA Responders (Reduction of Headache Days Greater Than 30%) vs. Non-responders and Saline | Treatment Month 1 - Baseline | 52.36 pmol/mg total protein | Standard Deviation 56.31 |
| Group A | Saliva CGRP Levels for OnabotulinumtoxinA Responders (Reduction of Headache Days Greater Than 30%) vs. Non-responders and Saline | Treatment Month 3 - Attack | 73.18 pmol/mg total protein | Standard Deviation 58.88 |
| Group A | Saliva CGRP Levels for OnabotulinumtoxinA Responders (Reduction of Headache Days Greater Than 30%) vs. Non-responders and Saline | Treatment Month 1 - 2 Hours Post | 61.55 pmol/mg total protein | Standard Deviation 44.82 |
| Group A | Saliva CGRP Levels for OnabotulinumtoxinA Responders (Reduction of Headache Days Greater Than 30%) vs. Non-responders and Saline | Treatment Month 3 - 2 Hours Post | 54.04 pmol/mg total protein | Standard Deviation 34.77 |
| Group B | Saliva CGRP Levels for OnabotulinumtoxinA Responders (Reduction of Headache Days Greater Than 30%) vs. Non-responders and Saline | Treatment Month 3 - 2 Hours Post | 19.11 pmol/mg total protein | Standard Deviation 13.24 |
| Group B | Saliva CGRP Levels for OnabotulinumtoxinA Responders (Reduction of Headache Days Greater Than 30%) vs. Non-responders and Saline | Treatment Month 1 - Baseline | 29.36 pmol/mg total protein | Standard Deviation 32.81 |
| Group B | Saliva CGRP Levels for OnabotulinumtoxinA Responders (Reduction of Headache Days Greater Than 30%) vs. Non-responders and Saline | Treatment Month 1 - Attack | 22.36 pmol/mg total protein | Standard Deviation 20.38 |
| Group B | Saliva CGRP Levels for OnabotulinumtoxinA Responders (Reduction of Headache Days Greater Than 30%) vs. Non-responders and Saline | Treatment Month 1 - 2 Hours Post | 23.66 pmol/mg total protein | Standard Deviation 12.11 |
| Group B | Saliva CGRP Levels for OnabotulinumtoxinA Responders (Reduction of Headache Days Greater Than 30%) vs. Non-responders and Saline | Treatment Month 2 - Baseline | 28.66 pmol/mg total protein | Standard Deviation 20.59 |
| Group B | Saliva CGRP Levels for OnabotulinumtoxinA Responders (Reduction of Headache Days Greater Than 30%) vs. Non-responders and Saline | Treatment Month 2 - Attack | 32.65 pmol/mg total protein | Standard Deviation 33.8 |
| Group B | Saliva CGRP Levels for OnabotulinumtoxinA Responders (Reduction of Headache Days Greater Than 30%) vs. Non-responders and Saline | Treatment Month 2 - 2 Hours Post | 22.35 pmol/mg total protein | Standard Deviation 19.94 |
| Group B | Saliva CGRP Levels for OnabotulinumtoxinA Responders (Reduction of Headache Days Greater Than 30%) vs. Non-responders and Saline | Treatment Month 3 - Baseline | 32.61 pmol/mg total protein | Standard Deviation 40.13 |
| Group B | Saliva CGRP Levels for OnabotulinumtoxinA Responders (Reduction of Headache Days Greater Than 30%) vs. Non-responders and Saline | Treatment Month 3 - Attack | 30.17 pmol/mg total protein | Standard Deviation 38.63 |
| Saline | Saliva CGRP Levels for OnabotulinumtoxinA Responders (Reduction of Headache Days Greater Than 30%) vs. Non-responders and Saline | Treatment Month 2 - 2 Hours Post | 33.93 pmol/mg total protein | Standard Deviation 35.91 |
| Saline | Saliva CGRP Levels for OnabotulinumtoxinA Responders (Reduction of Headache Days Greater Than 30%) vs. Non-responders and Saline | Treatment Month 1 - 2 Hours Post | 39.76 pmol/mg total protein | Standard Deviation 54.51 |
| Saline | Saliva CGRP Levels for OnabotulinumtoxinA Responders (Reduction of Headache Days Greater Than 30%) vs. Non-responders and Saline | Treatment Month 1 - Baseline | 70.46 pmol/mg total protein | Standard Deviation 98.26 |
| Saline | Saliva CGRP Levels for OnabotulinumtoxinA Responders (Reduction of Headache Days Greater Than 30%) vs. Non-responders and Saline | Treatment Month 3 - Baseline | 58.74 pmol/mg total protein | Standard Deviation 53.86 |
| Saline | Saliva CGRP Levels for OnabotulinumtoxinA Responders (Reduction of Headache Days Greater Than 30%) vs. Non-responders and Saline | Treatment Month 1 - Attack | 36.23 pmol/mg total protein | Standard Deviation 33.16 |
| Saline | Saliva CGRP Levels for OnabotulinumtoxinA Responders (Reduction of Headache Days Greater Than 30%) vs. Non-responders and Saline | Treatment Month 3 - 2 Hours Post | 49.39 pmol/mg total protein | Standard Deviation 43.81 |
| Saline | Saliva CGRP Levels for OnabotulinumtoxinA Responders (Reduction of Headache Days Greater Than 30%) vs. Non-responders and Saline | Treatment Month 2 - Attack | 33.05 pmol/mg total protein | Standard Deviation 30.96 |
| Saline | Saliva CGRP Levels for OnabotulinumtoxinA Responders (Reduction of Headache Days Greater Than 30%) vs. Non-responders and Saline | Treatment Month 2 - Baseline | 44.12 pmol/mg total protein | Standard Deviation 49.7 |
| Saline | Saliva CGRP Levels for OnabotulinumtoxinA Responders (Reduction of Headache Days Greater Than 30%) vs. Non-responders and Saline | Treatment Month 3 - Attack | 46.16 pmol/mg total protein | Standard Deviation 40.29 |