Skip to content

Ictal and Interictal Inflammatory Markers in Migraine

Ictal and Interictal Inflammatory Markers in Migraine

Status
Completed
Phases
Phase 4
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01138150
Enrollment
36
Registered
2010-06-07
Start date
2009-09-30
Completion date
2013-06-30
Last updated
2016-10-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Migraine

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.

DRUGPlacebo

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

University of Toledo Health Science Campus
CollaboratorOTHER
The Cleveland Clinic
CollaboratorOTHER
Johns Hopkins University
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Masking
TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No

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

MeasureTime frameDescription
Change in the Total Serum Adiponectin (T-ADP)30 minutes after treatment, 60 minutes after treatment, 120 minutes after treatmentChange in total serum adiponectin after treatment in responders and non responders

Secondary

MeasureTime frameDescription
Middle Molecular Weight (MMW)-ADP30 minutes after treatment, 60 minutes after treatment, 120 minutes after treatmentserum MMW-ADP levels after treatment in responders and non responders
Low Molecular Weight (LMW)-ADP30 minutes after treatment, 60 minutes after treatment, 120 minutes after treatmentserum LMW-ADP levels after treatment in responders and non responders
High Molecular Weight (HMW): T-ADP30 minutes, 60 minutes, 120 minutes after treatmentserum 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 treatmentserum HMW-ADP levels after treatment in responders and non responders
Leptin30 minutes after treatment, 60 minutes after treatment, 120 minutes after treatmentserum leptin levels after treatment in responders and non responders
Resistin30 minutes after treatment, 60 minutes after treatment, 120 minutes after treatmentserum resistin levels after treatment in responders and non responders
Low Molecular Weight (LMW):Total (T)-ADP30 minutes after treatment, 60 minutes after treatment, 120 minutes after treatmentserum 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

ArmCount
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
Total34

Withdrawals & dropouts

PeriodReasonFG000FG001
Overall Studyblood unable to be processed01
Overall StudyPhysician Decision10

Baseline characteristics

CharacteristicTreximetSugar PillTotal
Age, Categorical
<=18 years
0 Participants0 Participants0 Participants
Age, Categorical
>=65 years
0 Participants0 Participants0 Participants
Age, Categorical
Between 18 and 65 years
17 Participants17 Participants34 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
1 Participants1 Participants2 Participants
Race (NIH/OMB)
Black or African American
2 Participants1 Participants3 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants
Race (NIH/OMB)
White
14 Participants15 Participants29 Participants
Sex: Female, Male
Female
17 Participants15 Participants32 Participants
Sex: Female, Male
Male
0 Participants2 Participants2 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
— / —— / —
other
Total, other adverse events
0 / 170 / 17
serious
Total, serious adverse events
0 / 170 / 17

Outcome results

Primary

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

ArmMeasureValue (MEAN)
Treatment Responders 30 Minutes After TreatmentChange in the Total Serum Adiponectin (T-ADP)-0.96 ug/mL
Treatment Non-Responders 30 Minutes After TreatmentChange in the Total Serum Adiponectin (T-ADP)0.25 ug/mL
Treatment Responders 60 Minutes After TreatmentChange in the Total Serum Adiponectin (T-ADP)-0.97 ug/mL
Treatment Non-Responders 60 Minutes After TreatmentChange in the Total Serum Adiponectin (T-ADP)0.29 ug/mL
Treatment Responders 120 Minutes After TreatmentChange in the Total Serum Adiponectin (T-ADP)-0.98 ug/mL
Treatment Non-RespondersChange in the Total Serum Adiponectin (T-ADP)0.24 ug/mL
Secondary

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

ArmMeasureValue (MEAN)
Treatment Responders 30 Minutes After TreatmentHigh Molecular Weight (HMW)-Adiponectin (ADP)-0.24 ug/mL
Treatment Non-Responders 30 Minutes After TreatmentHigh Molecular Weight (HMW)-Adiponectin (ADP)-0.08 ug/mL
Treatment Responders 60 Minutes After TreatmentHigh Molecular Weight (HMW)-Adiponectin (ADP)-0.23 ug/mL
Treatment Non-Responders 60 Minutes After TreatmentHigh Molecular Weight (HMW)-Adiponectin (ADP)-0.14 ug/mL
Treatment Responders 120 Minutes After TreatmentHigh Molecular Weight (HMW)-Adiponectin (ADP)-0.24 ug/mL
Treatment Non-RespondersHigh Molecular Weight (HMW)-Adiponectin (ADP)-0.21 ug/mL
Secondary

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

ArmMeasureValue (MEAN)
Treatment Responders 30 Minutes After TreatmentHigh Molecular Weight (HMW): T-ADP-0.04 ratio
Treatment Non-Responders 30 Minutes After TreatmentHigh Molecular Weight (HMW): T-ADP0.01 ratio
Treatment Responders 60 Minutes After TreatmentHigh Molecular Weight (HMW): T-ADP-0.02 ratio
Treatment Non-Responders 60 Minutes After TreatmentHigh Molecular Weight (HMW): T-ADP0.01 ratio
Treatment Responders 120 Minutes After TreatmentHigh Molecular Weight (HMW): T-ADP0.01 ratio
Treatment Non-RespondersHigh Molecular Weight (HMW): T-ADP-0.02 ratio
Secondary

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

ArmMeasureValue (MEAN)
Treatment Responders 30 Minutes After TreatmentLeptin0.71 ug/mL
Treatment Non-Responders 30 Minutes After TreatmentLeptin0.89 ug/mL
Treatment Responders 60 Minutes After TreatmentLeptin0.28 ug/mL
Treatment Non-Responders 60 Minutes After TreatmentLeptin0.84 ug/mL
Treatment Responders 120 Minutes After TreatmentLeptin1.00 ug/mL
Treatment Non-RespondersLeptin0.02 ug/mL
Secondary

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

ArmMeasureValue (MEAN)
Treatment Responders 30 Minutes After TreatmentLow Molecular Weight (LMW)-ADP0.32 ug/mL
Treatment Non-Responders 30 Minutes After TreatmentLow Molecular Weight (LMW)-ADP-0.43 ug/mL
Treatment Responders 60 Minutes After TreatmentLow Molecular Weight (LMW)-ADP0.15 ug/mL
Treatment Non-Responders 60 Minutes After TreatmentLow Molecular Weight (LMW)-ADP-0.25 ug/mL
Treatment Responders 120 Minutes After TreatmentLow Molecular Weight (LMW)-ADP-0.45 ug/mL
Treatment Non-RespondersLow Molecular Weight (LMW)-ADP0.11 ug/mL
Secondary

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

ArmMeasureValue (MEAN)
Treatment Responders 30 Minutes After TreatmentLow Molecular Weight (LMW):Total (T)-ADP0.04 ratio
Treatment Non-Responders 30 Minutes After TreatmentLow Molecular Weight (LMW):Total (T)-ADP-0.04 ratio
Treatment Responders 60 Minutes After TreatmentLow Molecular Weight (LMW):Total (T)-ADP-0.01 ratio
Treatment Non-Responders 60 Minutes After TreatmentLow Molecular Weight (LMW):Total (T)-ADP0.02 ratio
Treatment Responders 120 Minutes After TreatmentLow Molecular Weight (LMW):Total (T)-ADP-0.04 ratio
Treatment Non-RespondersLow Molecular Weight (LMW):Total (T)-ADP0.01 ratio
Secondary

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

ArmMeasureValue (MEAN)
Treatment Responders 30 Minutes After TreatmentMiddle Molecular Weight (MMW)-ADP-0.02 ug/mL
Treatment Non-Responders 30 Minutes After TreatmentMiddle Molecular Weight (MMW)-ADP0.02 ug/mL
Treatment Responders 60 Minutes After TreatmentMiddle Molecular Weight (MMW)-ADP-0.03 ug/mL
Treatment Non-Responders 60 Minutes After TreatmentMiddle Molecular Weight (MMW)-ADP-0.02 ug/mL
Treatment Responders 120 Minutes After TreatmentMiddle Molecular Weight (MMW)-ADP0.16 ug/mL
Treatment Non-RespondersMiddle Molecular Weight (MMW)-ADP-0.03 ug/mL
Secondary

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

ArmMeasureValue (MEAN)
Treatment Responders 30 Minutes After TreatmentResistin-0.95 ug/mL
Treatment Non-Responders 30 Minutes After TreatmentResistin-0.97 ug/mL
Treatment Responders 60 Minutes After TreatmentResistin-1 ug/mL
Treatment Non-Responders 60 Minutes After TreatmentResistin-0.88 ug/mL
Treatment Responders 120 Minutes After TreatmentResistin-1.36 ug/mL
Treatment Non-RespondersResistin-0.79 ug/mL

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026