Ictal and Interictal Inflammatory Markers in Migraine

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.

Study Overview

• Status: Completed
• Conditions: Migraine
• Intervention / Treatment: Drug: Treximet; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • The Johns Hopkins Bayview Headache Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Treximet; Fourteen participants randomized to receive Treximet (sumatriptan & naproxen) during an acute migraine attack. Blood drawn for immune & inflammatory markers (adipocytokines,cytokines, sex hormones) at different time points - on presentation with moderate to severe migraine pain; then 30 minutes, 1 hour and 2 hours after administration of study drug (Treximet). Participants will be offered a traditional headache rescue medicine at 2 hours after administration of Treximet if participant still reports moderate to severe pain and desires further treatment. Rescue medicine may include the following: prochlorperazine 10 mg IV preceded by diphenhydramine 25 mg IV/PO or metoclopramide 10 mg IV preceded by diphenhydramine 25 mg IV/PO or Toradol 30 mg IV to be determined by the physician.	Drug: Treximet; 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.; Other Names: The brand name of sumatriptan/naproxen sodium is Treximet.
PLACEBO_COMPARATOR: Sugar Pill; Fourteen participants randomized to receive placebo during an acute migraine attack. Blood is drawn for immune & inflammatory markers (adipocytokines,cytokines), sex hormones at different time points - on presentation with moderate to severe migraine pain, then 30 minutes, 1 hour and 2 hours after administration of placebo. Participants will be offered a traditional headache rescue medicine at 2 hours after administration of placebo if participant still reports moderate to severe pain and desires further treatment. Rescue medicine may include the following: prochlorperazine 10 mg IV preceded by diphenhydramine 25 mg IV/PO or metoclopramide 10 mg IV preceded by diphenhydramine 25 mg IV/PO or Toradol 30 mg IV to be determined by the physician.	Drug: Placebo; One tablet of a sugar pill will be given upon subject presentation with an acute migraine attack and after blood levels have been drawn.; Other Names: Sugar Pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the Total Serum Adiponectin (T-ADP)	Change in total serum adiponectin after treatment in responders and non responders	30 minutes after treatment, 60 minutes after treatment, 120 minutes after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
High Molecular Weight (HMW)-Adiponectin (ADP)	serum HMW-ADP levels after treatment in responders and non responders	30 minutes after treatment, 60 minutes after treatment, 120 minutes after treatment
Middle Molecular Weight (MMW)-ADP	serum MMW-ADP levels after treatment in responders and non responders	30 minutes after treatment, 60 minutes after treatment, 120 minutes after treatment
Low Molecular Weight (LMW)-ADP	serum LMW-ADP levels after treatment in responders and non responders	30 minutes after treatment, 60 minutes after treatment, 120 minutes after treatment
High Molecular Weight (HMW): T-ADP	serum HMW:T-ADP levels after treatment in responders and non responders	30 minutes, 60 minutes, 120 minutes after treatment
Low Molecular Weight (LMW):Total (T)-ADP	serum LMW:T-ADP levels after treatment in responders and non responders	30 minutes after treatment, 60 minutes after treatment, 120 minutes after treatment
Leptin	serum leptin levels after treatment in responders and non responders	30 minutes after treatment, 60 minutes after treatment, 120 minutes after treatment
Resistin	serum resistin levels after treatment in responders and non responders	30 minutes after treatment, 60 minutes after treatment, 120 minutes after treatment

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: The Cleveland Clinic; University of Toledo Health Science Campus

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (ACTUAL): June 1, 2013
• Study Completion (ACTUAL): June 1, 2013

Study Registration Dates

• First Submitted: June 3, 2010
• First Submitted That Met QC Criteria: June 3, 2010
• First Posted (ESTIMATE): June 7, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): October 6, 2016
• Last Update Submitted That Met QC Criteria: August 15, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: migraine, headache, sumatriptan, naproxen sodium
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Serotonin Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Gout Suppressants; Vasoconstrictor Agents; Naproxen; Sumatriptan
• Other Study ID Numbers: GSK112035

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO