Migraine Headache
Conditions
Brief summary
Migraine is a common neurological condition that can be disabling, particularly if chronic. Greater occipital nerve (GON) block has been utilized for decades for the treatment of migraine in the absence of a single randomized, placebo-controlled trial documenting its effectiveness. Hypothesis: Greater occipital nerve block reduces the frequency of days with moderate or severe headache in patients with episodic or chronic migraine.
Detailed description
Migraine is a common disease with lifetime prevalence in women and men of 33% and 12% respectively. Chronic migraine affects 2% of the US population and is highly disabling. There are no FDA approved medications for the treatment of chronic migraine. Although some patients benefit from a daily prophylactic medication, others continue to suffer from severe, frequent, debilitating headaches. Limited efficacy, poor compliance, side effects and drug-drug interactions may explain why more than 80% of migraineurs in the population are not prescribed daily prophylactic medications. Occipital nerve injections with corticosteroids and/or local anesthetics have been employed for the acute and prophylactic treatment of migraine, cervicogenic headache and cluster headache for decades. A long-acting anesthetic and corticosteroid are often combined, although anesthetic agents have also been used alone. However, there are no randomized controlled trials evaluating the preventive efficacy of occipital nerve block in subjects with migraine. Patients were equally randomized to receive either 2.5 ml 0.5% bupivacaine plus 0.5 ml 20 mg methylprednisolone over the ipsilateral (unilateral headache) or bilateral (bilateral headache) occipital nerve or 2.75 ml normal saline plus 0.25 ml 1% lidocaine without epinephrine (placebo). The GON injection site was at the medial third of the distance between the occipital protuberance and the mastoid process. Patients were evaluated after the 4-week baseline diary completion phase to undergo the injection, and for 4 weeks after the injection. Therefore, there were 3 patient visits in this study: screening, injection and 4-week follow-up. In an effort to ensure adequate blinding, 0.25 ml of short-acting 1% lidocaine without epinephrine was used as the placebo arm. In order to ensure adequate blinding of the investigator, each syringe and needle hub was covered with opaque tape so as to ensure blinding of the investigator providing the injection. A total of four investigators provided injections. The blinded investigator who evaluated the study subject 4 weeks after injection may or may not be the same as the investigator who provided the injection.
Interventions
DRUGbupivicaine
2.5 mL 0.5% bupivicaine
DRUGnormal saline
2.75 mL normal saline
DRUGmethylprednisolone
0.5 mL 20 mg methylprednisolone
DRUGlidocaine
0.25 mL 1% lidocaine
Sponsors
National Center for Advancing Translational Sciences (NCATS)
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Subjects meet diagnostic criteria for episodic migraine or chronic migraine according to the International Headache Classification II (ICHD-II) * Migraine sufferers who experience at least 1 attack per week * Able to read and understand the requirements of the study, abide by any restrictions, and return for the required examinations * Able and willing to sign an informed consent statement * Subjects must be in generally good health as confirmed by medical history, medication review, baseline physical examination, vital signs and clinical laboratory evaluations.
Exclusion criteria
* Subjects with continuous headache (no headache free periods) * Subjects using maintenance opioid medication * Subjects who have started a medication with prophylactic migraine efficacy within the past 2 months * Known hypersensitivity or allergic reaction to any of study ingredients (lidocaine, bupivicaine, any local anesthetics, and corticosteroids) or betadine. * Use of any investigational medication within 90 days of the initial screening visit and/or concurrent enrolment in an investigational study * Injection site infection or systemic infection at the injection visit (afebrile at time of injection) * Presence of cranial bone defect * Subjects with chronic cluster headache, new daily persistent headache, hemicrania continua, or chronic tension type headache * Subjects with a history of an unstable medical condition (e.g. cardiovascular, hepatic, renal, endocrine) that may impair their reliable participation in the study or necessitate the use of medications not permitted in this study * Subjects with a history (within the past 6 months) of a major psychiatric disorder that in the opinion of the investigator may preclude the subject from completed the requirements of the study * Female subjects who are pregnant or nursing * Subjects with a history of drug or alcohol abuse within the past 2 years * Subjects with a history of poor compliance with past drug therapies, as judged by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With at Least 50% Reduction in the Frequency of Days With Moderate or Severe Migraine in the 4 Week Post Injection Compared to the 4 Week Pre-injection Baseline Period | 4 weeks pre-injection baseline, 4 weeks post-injection | The baseline frequency will be the number of calendar days with moderate or severe migraine during the 4 week period prior to injection, and the follow-up frequency will be the number of calendar days with migraine during the 4 week period following injection. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Frequency of Days With a Migraine | 4 weeks post-injection | — |
| Mean Number of Hours With Moderate or Severe Migraine | 4 weeks post-injection | — |
| Mean Number of Days With Acute Medication Use | 4 weeks post-injection | Acute medication use meant the consumption of a drug to abort or terminate a headache. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited by referral from multiple neurologists in the division of Headache at Mayo Clinic in Arizona from June 2009 to October 2012.
Participants by arm
| Arm | Count |
|---|---|
| Active Injection Subjects randomized to this arm will receive 2.5 mL 0.5% bupivicaine plus 0.5 mL 20 mg methylprednisolone injected over the ipsilateral (unilateral headache) or bilateral (bilateral headache) occipital nerve. | 35 |
| Placebo Injection Subjects randomized to this arm will receive 2.75 mL normal saline plus 0.25 mL 1% lidocaine injected over the ipsilateral (unilateral headache) or bilateral (bilateral headache) occipital nerve. | 35 |
| Total | 70 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| 4-week Follow Up | Lost to Follow-up | 1 | 5 |
| Screening | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Active Injection | Placebo Injection | Total |
|---|---|---|---|
| Age, Continuous | 44 years STANDARD_DEVIATION 11 | 43 years STANDARD_DEVIATION 15 | 43 years STANDARD_DEVIATION 14 |
| Region of Enrollment United States | 35 participants | 35 participants | 70 participants |
| Sex: Female, Male Female | 31 Participants | 28 Participants | 59 Participants |
| Sex: Female, Male Male | 4 Participants | 7 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 34 | 7 / 35 |
| serious Total, serious adverse events | 0 / 34 | 1 / 35 |
Outcome results
Primary
Number of Subjects With at Least 50% Reduction in the Frequency of Days With Moderate or Severe Migraine in the 4 Week Post Injection Compared to the 4 Week Pre-injection Baseline Period
The baseline frequency will be the number of calendar days with moderate or severe migraine during the 4 week period prior to injection, and the follow-up frequency will be the number of calendar days with migraine during the 4 week period following injection.
Time frame: 4 weeks pre-injection baseline, 4 weeks post-injection
Population: Because of missing data, 33 subjects in the active arm and 30 subjects in the placebo arm were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active Injection | Number of Subjects With at Least 50% Reduction in the Frequency of Days With Moderate or Severe Migraine in the 4 Week Post Injection Compared to the 4 Week Pre-injection Baseline Period | 10 participants |
| Placebo Injection | Number of Subjects With at Least 50% Reduction in the Frequency of Days With Moderate or Severe Migraine in the 4 Week Post Injection Compared to the 4 Week Pre-injection Baseline Period | 9 participants |
p-value: 0.98Chi-squared
Secondary
Mean Frequency of Days With a Migraine
Time frame: 4 weeks post-injection
Population: Because of missing data, 33 subjects in the active arm and 30 subjects in the placebo arm were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active Injection | Mean Frequency of Days With a Migraine | Severe | 3.4 days per 4 weeks | Standard Deviation 3.4 |
| Active Injection | Mean Frequency of Days With a Migraine | At Least Moderate | 7.0 days per 4 weeks | Standard Deviation 4.2 |
| Active Injection | Mean Frequency of Days With a Migraine | At Least Mild | 9.3 days per 4 weeks | Standard Deviation 4.8 |
| Placebo Injection | Mean Frequency of Days With a Migraine | Severe | 2.9 days per 4 weeks | Standard Deviation 2.7 |
| Placebo Injection | Mean Frequency of Days With a Migraine | At Least Moderate | 7.8 days per 4 weeks | Standard Deviation 5.8 |
| Placebo Injection | Mean Frequency of Days With a Migraine | At Least Mild | 10.4 days per 4 weeks | Standard Deviation 6.8 |
Comparison: Severe Migraine Frequencyp-value: 0.52t-test, 2 sided
Comparison: At least Moderate Migraine Frequencyp-value: 0.52t-test, 2 sided
Comparison: At Least Mild Migraine Frequencyp-value: 0.47t-test, 2 sided
Secondary
Mean Number of Days With Acute Medication Use
Acute medication use meant the consumption of a drug to abort or terminate a headache.
Time frame: 4 weeks post-injection
Population: Because of missing data, 33 subjects in the active arm and 30 subjects in the placebo arm were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Injection | Mean Number of Days With Acute Medication Use | 6.7 days per 4 weeks | Standard Deviation 4.2 |
| Placebo Injection | Mean Number of Days With Acute Medication Use | 7.7 days per 4 weeks | Standard Deviation 6.3 |
p-value: 0.47t-test, 2 sided
Secondary
Mean Number of Hours With Moderate or Severe Migraine
Time frame: 4 weeks post-injection
Population: Because of missing data, 33 subjects in the active arm and 30 subjects in the placebo arm were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Injection | Mean Number of Hours With Moderate or Severe Migraine | 60 hours per 4 weeks | Standard Deviation 72 |
| Placebo Injection | Mean Number of Hours With Moderate or Severe Migraine | 58 hours per 4 weeks | Standard Deviation 60 |
p-value: 0.9t-test, 2 sided