Migraine
Conditions
Keywords
migraine, headache, sumatriptan, naproxen sodium
Brief summary
The purpose of this study is to evaluate blood levels of several proteins that may be altered in the inflammation associated with migraine headaches. These blood levels will be evaluated in individuals during an acute migraine attack and compared to their levels when pain free. The investigators study hypothesis is that the pro inflammatory proteins in the blood will be greater than the levels of these proteins when evaluated during a pain free period.
Detailed description
Migraine is a common, chronic disorder, which presents with recurrent episodes of disabling headache and affects approximately 12% of American adults.1,2 No biomarkers exist to identify episodic or chronic migraine sufferers; and the diagnosis relies solely on clinical criteria. Further the full pathophysiology of migraine has not been fully delineated, although our understanding of migraine pathophysiology has dramatically improved over the past 15 years. Current theories suggest that migraine is a neurovascular disorder, with the pain of migraine a result of the release of inflammatory neuropeptides from nerve endings in the activated trigeminal system (neurogenic inflammation), ultimately resulting in vasodilation, plasma extravasation and mast cell degranulation.3-6 Several inflammatory markers have been implicated in the pathway resulting in the neurogenic inflammation of migraine including calcitonin gene related peptide (CGRP), substance P (SP), neurokinin A, and multiple cytokines such as interleukin (IL) -1, IL-6 and tumor necrosis-α (TNF-α).5,7-10 More recent research supports that the odds of migraine are increased in those who are obese and that several adipose tissue derived cytokines (adipocytokines) may contribute to the neurogenic inflammation of migraine, including leptin and adiponectin. In one small pilot study of 33 participants evaluating chronic and episodic migraineurs as compared to controls, adiponectin (an adipocytokine) was significantly elevated in chronic migraineurs as compared to controls. A second study reported low levels of another adipocytokine, leptin in episodic migraineurs. However, all of these studies have evaluated only 3 to 4 of cytokines at the same time point and 11 none have evaluated adipocytokines during an acute attack. We hypothesize that obesity-related cytokines contribute to the neurogenic inflammation of migraine and have the potential be useful as biomarkers for episodic and chronic migraine as well as new drug targets for the treatment of migraine. To this end we propose to evaluate serum levels of obesity-related cytokines in migraineurs, ictally (during an acute migraine attack), following treatment with sumatriptan/naproxen sodium (Treximet®) and interictally (at baseline) when pain free.
Interventions
One tablet of sumatriptan 85 mg and naproxen sodium 500 mg will be given upon subject presentation with an acute migraine attack and after blood levels have been drawn.
One tablet of a sugar pill will be given upon subject presentation with an acute migraine attack and after blood levels have been drawn.
Sponsors
Study design
Eligibility
Inclusion criteria
* Age greater than 18 years of age, migraine
Exclusion criteria
* Pregnant or breast-feeding women, presence of cardiovascular or cerebrovascular disorders as well as any known inflammatory, infectious, metabolic, thyroid, renal, cardiovascular or gastrointestinal diseases
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Total Serum Adiponectin (T-ADP) | 30 minutes after treatment, 60 minutes after treatment, 120 minutes after treatment | Change in total serum adiponectin after treatment in responders and non responders |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Middle Molecular Weight (MMW)-ADP | 30 minutes after treatment, 60 minutes after treatment, 120 minutes after treatment | serum MMW-ADP levels after treatment in responders and non responders |
| Low Molecular Weight (LMW)-ADP | 30 minutes after treatment, 60 minutes after treatment, 120 minutes after treatment | serum LMW-ADP levels after treatment in responders and non responders |
| High Molecular Weight (HMW): T-ADP | 30 minutes, 60 minutes, 120 minutes after treatment | serum HMW:T-ADP levels after treatment in responders and non responders |
| High Molecular Weight (HMW)-Adiponectin (ADP) | 30 minutes after treatment, 60 minutes after treatment, 120 minutes after treatment | serum HMW-ADP levels after treatment in responders and non responders |
| Leptin | 30 minutes after treatment, 60 minutes after treatment, 120 minutes after treatment | serum leptin levels after treatment in responders and non responders |
| Resistin | 30 minutes after treatment, 60 minutes after treatment, 120 minutes after treatment | serum resistin levels after treatment in responders and non responders |
| Low Molecular Weight (LMW):Total (T)-ADP | 30 minutes after treatment, 60 minutes after treatment, 120 minutes after treatment | serum LMW:T-ADP levels after treatment in responders and non responders |
Countries
United States
Participant flow
Recruitment details
Dates of recruitment - December 9 2010 through January 22, 2013. Types of location - Neurology Headache Clinic, Internal Medicine Clinics, Gynecology clinic; study flyers placed in the medical offices , Johns Hopkins Community Physicians sites, academic institutions and wellness centers.
Participants by arm
| Arm | Count |
|---|---|
| Treximet Participants randomized to active drug Treximet during acute migraine attack. | 17 |
| Sugar Pill Participants randomized to placebo (sugar pill) during acute migraine attack. | 17 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | blood unable to be processed | 0 | 1 |
| Overall Study | Physician Decision | 1 | 0 |
Baseline characteristics
| Characteristic | Treximet | Sugar Pill | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants | 17 Participants | 34 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 14 Participants | 15 Participants | 29 Participants |
| Sex: Female, Male Female | 17 Participants | 15 Participants | 32 Participants |
| Sex: Female, Male Male | 0 Participants | 2 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 17 | 0 / 17 |
| serious Total, serious adverse events | 0 / 17 | 0 / 17 |
Outcome results
Change in the Total Serum Adiponectin (T-ADP)
Change in total serum adiponectin after treatment in responders and non responders
Time frame: 30 minutes after treatment, 60 minutes after treatment, 120 minutes after treatment
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment Responders 30 Minutes After Treatment | Change in the Total Serum Adiponectin (T-ADP) | -0.96 ug/mL |
| Treatment Non-Responders 30 Minutes After Treatment | Change in the Total Serum Adiponectin (T-ADP) | 0.25 ug/mL |
| Treatment Responders 60 Minutes After Treatment | Change in the Total Serum Adiponectin (T-ADP) | -0.97 ug/mL |
| Treatment Non-Responders 60 Minutes After Treatment | Change in the Total Serum Adiponectin (T-ADP) | 0.29 ug/mL |
| Treatment Responders 120 Minutes After Treatment | Change in the Total Serum Adiponectin (T-ADP) | -0.98 ug/mL |
| Treatment Non-Responders | Change in the Total Serum Adiponectin (T-ADP) | 0.24 ug/mL |
High Molecular Weight (HMW)-Adiponectin (ADP)
serum HMW-ADP levels after treatment in responders and non responders
Time frame: 30 minutes after treatment, 60 minutes after treatment, 120 minutes after treatment
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment Responders 30 Minutes After Treatment | High Molecular Weight (HMW)-Adiponectin (ADP) | -0.24 ug/mL |
| Treatment Non-Responders 30 Minutes After Treatment | High Molecular Weight (HMW)-Adiponectin (ADP) | -0.08 ug/mL |
| Treatment Responders 60 Minutes After Treatment | High Molecular Weight (HMW)-Adiponectin (ADP) | -0.23 ug/mL |
| Treatment Non-Responders 60 Minutes After Treatment | High Molecular Weight (HMW)-Adiponectin (ADP) | -0.14 ug/mL |
| Treatment Responders 120 Minutes After Treatment | High Molecular Weight (HMW)-Adiponectin (ADP) | -0.24 ug/mL |
| Treatment Non-Responders | High Molecular Weight (HMW)-Adiponectin (ADP) | -0.21 ug/mL |
High Molecular Weight (HMW): T-ADP
serum HMW:T-ADP levels after treatment in responders and non responders
Time frame: 30 minutes, 60 minutes, 120 minutes after treatment
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment Responders 30 Minutes After Treatment | High Molecular Weight (HMW): T-ADP | -0.04 ratio |
| Treatment Non-Responders 30 Minutes After Treatment | High Molecular Weight (HMW): T-ADP | 0.01 ratio |
| Treatment Responders 60 Minutes After Treatment | High Molecular Weight (HMW): T-ADP | -0.02 ratio |
| Treatment Non-Responders 60 Minutes After Treatment | High Molecular Weight (HMW): T-ADP | 0.01 ratio |
| Treatment Responders 120 Minutes After Treatment | High Molecular Weight (HMW): T-ADP | 0.01 ratio |
| Treatment Non-Responders | High Molecular Weight (HMW): T-ADP | -0.02 ratio |
Leptin
serum leptin levels after treatment in responders and non responders
Time frame: 30 minutes after treatment, 60 minutes after treatment, 120 minutes after treatment
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment Responders 30 Minutes After Treatment | Leptin | 0.71 ug/mL |
| Treatment Non-Responders 30 Minutes After Treatment | Leptin | 0.89 ug/mL |
| Treatment Responders 60 Minutes After Treatment | Leptin | 0.28 ug/mL |
| Treatment Non-Responders 60 Minutes After Treatment | Leptin | 0.84 ug/mL |
| Treatment Responders 120 Minutes After Treatment | Leptin | 1.00 ug/mL |
| Treatment Non-Responders | Leptin | 0.02 ug/mL |
Low Molecular Weight (LMW)-ADP
serum LMW-ADP levels after treatment in responders and non responders
Time frame: 30 minutes after treatment, 60 minutes after treatment, 120 minutes after treatment
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment Responders 30 Minutes After Treatment | Low Molecular Weight (LMW)-ADP | 0.32 ug/mL |
| Treatment Non-Responders 30 Minutes After Treatment | Low Molecular Weight (LMW)-ADP | -0.43 ug/mL |
| Treatment Responders 60 Minutes After Treatment | Low Molecular Weight (LMW)-ADP | 0.15 ug/mL |
| Treatment Non-Responders 60 Minutes After Treatment | Low Molecular Weight (LMW)-ADP | -0.25 ug/mL |
| Treatment Responders 120 Minutes After Treatment | Low Molecular Weight (LMW)-ADP | -0.45 ug/mL |
| Treatment Non-Responders | Low Molecular Weight (LMW)-ADP | 0.11 ug/mL |
Low Molecular Weight (LMW):Total (T)-ADP
serum LMW:T-ADP levels after treatment in responders and non responders
Time frame: 30 minutes after treatment, 60 minutes after treatment, 120 minutes after treatment
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment Responders 30 Minutes After Treatment | Low Molecular Weight (LMW):Total (T)-ADP | 0.04 ratio |
| Treatment Non-Responders 30 Minutes After Treatment | Low Molecular Weight (LMW):Total (T)-ADP | -0.04 ratio |
| Treatment Responders 60 Minutes After Treatment | Low Molecular Weight (LMW):Total (T)-ADP | -0.01 ratio |
| Treatment Non-Responders 60 Minutes After Treatment | Low Molecular Weight (LMW):Total (T)-ADP | 0.02 ratio |
| Treatment Responders 120 Minutes After Treatment | Low Molecular Weight (LMW):Total (T)-ADP | -0.04 ratio |
| Treatment Non-Responders | Low Molecular Weight (LMW):Total (T)-ADP | 0.01 ratio |
Middle Molecular Weight (MMW)-ADP
serum MMW-ADP levels after treatment in responders and non responders
Time frame: 30 minutes after treatment, 60 minutes after treatment, 120 minutes after treatment
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment Responders 30 Minutes After Treatment | Middle Molecular Weight (MMW)-ADP | -0.02 ug/mL |
| Treatment Non-Responders 30 Minutes After Treatment | Middle Molecular Weight (MMW)-ADP | 0.02 ug/mL |
| Treatment Responders 60 Minutes After Treatment | Middle Molecular Weight (MMW)-ADP | -0.03 ug/mL |
| Treatment Non-Responders 60 Minutes After Treatment | Middle Molecular Weight (MMW)-ADP | -0.02 ug/mL |
| Treatment Responders 120 Minutes After Treatment | Middle Molecular Weight (MMW)-ADP | 0.16 ug/mL |
| Treatment Non-Responders | Middle Molecular Weight (MMW)-ADP | -0.03 ug/mL |
Resistin
serum resistin levels after treatment in responders and non responders
Time frame: 30 minutes after treatment, 60 minutes after treatment, 120 minutes after treatment
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment Responders 30 Minutes After Treatment | Resistin | -0.95 ug/mL |
| Treatment Non-Responders 30 Minutes After Treatment | Resistin | -0.97 ug/mL |
| Treatment Responders 60 Minutes After Treatment | Resistin | -1 ug/mL |
| Treatment Non-Responders 60 Minutes After Treatment | Resistin | -0.88 ug/mL |
| Treatment Responders 120 Minutes After Treatment | Resistin | -1.36 ug/mL |
| Treatment Non-Responders | Resistin | -0.79 ug/mL |