Ictal and Interictal Inflammatory Markers in Migraine

• Sponsor: Johns Hopkins University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01138150
• Collaborator: University of Toledo Health Science Campus (Other), The Cleveland Clinic (Other)
• Enrollment: 36
• Location: 1
• Arms: 2
• Duration (Months): 45
• Patients Per Site Per Month: 0.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Migraine	Drug: Treximet; Drug: Placebo	Phase 4

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 Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Official Title: Ictal and Interictal Inflammatory Markers in Migraine
• Study Start Date: Sep 1, 2009
• Actual Primary Completion Date: Jun 1, 2013
• Actual Study Completion Date: Jun 1, 2013

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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

2. 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

3. 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

4. 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

5. 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

6. Leptin [30 minutes after treatment, 60 minutes after treatment, 120 minutes after treatment]

   serum leptin levels after treatment in responders and non responders

7. Resistin [30 minutes after treatment, 60 minutes after treatment, 120 minutes after treatment]

   serum resistin levels after treatment in responders and non responders

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Johns Hopkins Bayview Headache Center	Baltimore	Maryland	United States	21224

Sponsors and Collaborators

• Johns Hopkins University
• University of Toledo Health Science Campus
• The Cleveland Clinic

Investigators

• Principal Investigator: Barbara L Peterlin, DO, The Johns Hopkins University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT01138150
• Other Study ID Numbers: GSK112035; NCT00868322
• First Posted: Jun 7, 2010
• Last Update Posted: Oct 6, 2016
• Last Verified: Aug 1, 2016

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Johns Hopkins University: migraine, headache, sumatriptan, naproxen sodium
• Additional relevant MeSH terms: Migraine Disorders; Naproxen; Sumatriptan

Study Results

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.

Arm/Group Title	Active Drug - Sumatriptan/Naproxen	Placebo
Arm/Group Description	Participants randomized to sumatriptan/naproxen upon presentation of migraine acute attack	Participants randomized to placebo upon presentation with acute migraine attack.
Period Title: Overall Study
STARTED	18	18
COMPLETED	17	17
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	Treximet	Sugar Pill	Total
Arm/Group Description	Participants randomized to active drug Treximet during acute migraine attack.	Participants randomized to placebo (sugar pill) during acute migraine attack.	Total of all reporting groups
Overall Participants	17	17	34
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	17 100%	17 100%	34 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	17 100%	15 88.2%	32 94.1%
Male	0 0%	2 11.8%	2 5.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 5.9%	1 5.9%	2 5.9%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 11.8%	1 5.9%	3 8.8%
White	14 82.4%	15 88.2%	29 85.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Change in the Total Serum Adiponectin (T-ADP)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment Responders 30 Minutes After Treatment	Treatment Non-Responders 30 Minutes After Treatment	Treatment Responders 60 Minutes After Treatment	Treatment Non-Responders 60 Minutes After Treatment	Treatment Responders 120 Minutes After Treatment	Treatment Non-Responders
Arm/Group Description	Treatment responders are defined as those with a reduction of pain from moderate to severe at T0 (before treatment) to none to mild 30 minutes after treatment with Treximet or sugar pill.	Treatment non-responders are defined as those without a reduction of pain from moderate to severe at T0 (before treatment) to none to mild 30 minutes after after treatment with Treximet or sugar pill.	Treatment responders are defined as those with a reduction of pain from moderate to severe at T0 (before treatment) to none to mild 60 minutes after treatment with Treximet or sugar pill.	Treatment non-responders are defined as those without a reduction of pain from moderate to severe at T0 (before treatment) to none to mild 60 minutes after treatment with Treximet or sugar pill.	Treatment responders are defined as those with a reduction of pain from moderate to severe at T0 (before treatment) to none to mild 120 minutes after treatment with Treximet or sugar pill.	Treatment non-responders are defined as those without a reduction of pain from moderate to severe at T0 (before treatment) to none to mild 120 minutes after treatment with Treximet or sugar pill.
Measure Participants	17	17	17	17	17	17
Mean (95% Confidence Interval) [ug/mL]	-0.96	0.25	-0.97	0.29	-0.98	0.24

2. Secondary Outcome

Title	High Molecular Weight (HMW)-Adiponectin (ADP)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment Responders 120 Minutes After Treatment	Treatment Non Responders 120 Minutes After Treatment	Treatment Responders 30 Minutes After Treatment	Treatment Non-Responders 30 Minutes After Treatment	Treatment Non-Responders 60 Minutes After Treatment	Treatment Responders 60 Minutes After Treatment
Arm/Group Description	Treatment responders were defined as those with a reduction of pain from moderate to severe (>=4/10 on the NRS) at T0 to no to mild (<=3/10 on the NRS) at 120 minutes after treatment with either sumatriptan/naproxen or placebo	Participants without reduction in pain at 120 minutes after treatment	Treatment responders were defined as those with a reduction of pain from moderate to severe (>=4/10 on the NRS) at T0 to no to mild (<=3/10 on the NRS) at 120 minutes after treatment with either sumatriptan/naproxen or placebo	Participants without reduction in pain at 120 minutes after treatment	Participants without reduction in pain at 120 minutes after treatment	Treatment responders were defined as those with a reduction of pain from moderate to severe (>=4/10 on the NRS) at T0 to no to mild (<=3/10 on the NRS) at 120 minutes after treatment with either sumatriptan/naproxen or placebo
Measure Participants	17	17	17	17	17	17
Mean (95% Confidence Interval) [ug/mL]	-0.24	-0.08	-0.23	-0.14	-0.24	-0.21

3. Secondary Outcome

Title	Middle Molecular Weight (MMW)-ADP
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment Responders 120 Minutes After Treatment	Treatment Non Responders 120 Minutes After Treatment	Treatment Responders 30 Minutes After Treatment	Treatment Non-Responders 30 Minutes After Treatment	Treatment Non-Responders 60 Minutes After Treatment	Treatment Responders 60 Minutes After Treatment
Arm/Group Description	Treatment responders were defined as those with a reduction of pain from moderate to severe (>=4/10 on the NRS) at T0 to no to mild (<=3/10 on the NRS) at 120 minutes after treatment with either sumatriptan/naproxen or placebo	Participants without reduction in pain at 120 minutes after treatment	Treatment responders were defined as those with a reduction of pain from moderate to severe (>=4/10 on the NRS) at T0 to no to mild (<=3/10 on the NRS) at 120 minutes after treatment with either sumatriptan/naproxen or placebo	Participants without reduction in pain at 120 minutes after treatment	Participants without reduction in pain at 120 minutes after treatment	Treatment responders were defined as those with a reduction of pain from moderate to severe (>=4/10 on the NRS) at T0 to no to mild (<=3/10 on the NRS) at 120 minutes after treatment with either sumatriptan/naproxen or placebo
Measure Participants	17	17	17	17	17	17
Mean (95% Confidence Interval) [ug/mL]	-0.02	0.02	-0.03	-0.02	0.16	-0.03

4. Secondary Outcome

Title	Low Molecular Weight (LMW)-ADP
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment Responders 120 Minutes After Treatment	Treatment Non Responders 120 Minutes After Treatment	Treatment Responders 30 Minutes After Treatment	Treatment Non-Responders 30 Minutes After Treatment	Treatment Non-Responders 60 Minutes After Treatment	Treatment Responders 60 Minutes After Treatment
Arm/Group Description	Treatment responders were defined as those with a reduction of pain from moderate to severe (>=4/10 on the NRS) at T0 to no to mild (<=3/10 on the NRS) at 120 minutes after treatment with either sumatriptan/naproxen or placebo	Participants without reduction in pain at 120 minutes after treatment	Treatment responders were defined as those with a reduction of pain from moderate to severe (>=4/10 on the NRS) at T0 to no to mild (<=3/10 on the NRS) at 120 minutes after treatment with either sumatriptan/naproxen or placebo	Participants without reduction in pain at 120 minutes after treatment	Participants without reduction in pain at 120 minutes after treatment	Treatment responders were defined as those with a reduction of pain from moderate to severe (>=4/10 on the NRS) at T0 to no to mild (<=3/10 on the NRS) at 120 minutes after treatment with either sumatriptan/naproxen or placebo
Measure Participants	17	17	17	17	17	17
Mean (95% Confidence Interval) [ug/mL]	0.32	-0.43	0.15	-0.25	-0.45	0.11

5. Secondary Outcome

Title	High Molecular Weight (HMW): T-ADP
Description	serum HMW:T-ADP levels after treatment in responders and non responders
Time Frame	30 minutes, 60 minutes, 120 minutes after treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment Responders 120 Minutes After Treatment	Treatment Non Responders 120 Minutes After Treatment	Treatment Responders 30 Minutes After Treatment	Treatment Non-Responders 30 Minutes After Treatment	Treatment Non-Responders 60 Minutes After Treatment	Treatment Responders 60 Minutes After Treatment
Arm/Group Description	Treatment responders were defined as those with a reduction of pain from moderate to severe (>=4/10 on the NRS) at T0 to no to mild (<=3/10 on the NRS) at 120 minutes after treatment with either sumatriptan/naproxen or placebo	Participants without reduction in pain at 120 minutes after treatment	Treatment responders were defined as those with a reduction of pain from moderate to severe (>=4/10 on the NRS) at T0 to no to mild (<=3/10 on the NRS) at 120 minutes after treatment with either sumatriptan/naproxen or placebo	Participants without reduction in pain at 120 minutes after treatment	Participants without reduction in pain at 120 minutes after treatment	Treatment responders were defined as those with a reduction of pain from moderate to severe (>=4/10 on the NRS) at T0 to no to mild (<=3/10 on the NRS) at 120 minutes after treatment with either sumatriptan/naproxen or placebo
Measure Participants	17	17	17	17	17	17
Mean (95% Confidence Interval) [ratio]	-0.04	0.01	-0.02	0.01	0.01	-0.02

6. Secondary Outcome

Title	Low Molecular Weight (LMW):Total (T)-ADP
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment Responders 120 Minutes After Treatment	Treatment Non Responders 120 Minutes After Treatment	Treatment Responders 30 Minutes After Treatment	Treatment Non-Responders 30 Minutes After Treatment	Treatment Non-Responders 60 Minutes After Treatment	Treatment Responders 60 Minutes After Treatment
Arm/Group Description	Treatment responders were defined as those with a reduction of pain from moderate to severe (>=4/10 on the NRS) at T0 to no to mild (<=3/10 on the NRS) at 120 minutes after treatment with either sumatriptan/naproxen or placebo	Participants without reduction in pain at 120 minutes after treatment	Treatment responders were defined as those with a reduction of pain from moderate to severe (>=4/10 on the NRS) at T0 to no to mild (<=3/10 on the NRS) at 120 minutes after treatment with either sumatriptan/naproxen or placebo	Participants without reduction in pain at 120 minutes after treatment	Participants without reduction in pain at 120 minutes after treatment	Treatment responders were defined as those with a reduction of pain from moderate to severe (>=4/10 on the NRS) at T0 to no to mild (<=3/10 on the NRS) at 120 minutes after treatment with either sumatriptan/naproxen or placebo
Measure Participants	17	17	17	17	17	17
Mean (95% Confidence Interval) [ratio]	0.04	-0.04	-0.01	0.02	-0.04	0.01

7. Secondary Outcome

Title	Leptin
Description	serum leptin levels after treatment in responders and non responders
Time Frame	30 minutes after treatment, 60 minutes after treatment, 120 minutes after treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment Responders 120 Minutes After Treatment	Treatment Non Responders 120 Minutes After Treatment	Treatment Responders 30 Minutes After Treatment	Treatment Non-Responders 30 Minutes After Treatment	Treatment Non-Responders 60 Minutes After Treatment	Treatment Responders 60 Minutes After Treatment
Arm/Group Description	Treatment responders were defined as those with a reduction of pain from moderate to severe (>=4/10 on the NRS) at T0 to no to mild (<=3/10 on the NRS) at 120 minutes after treatment with either sumatriptan/naproxen or placebo	Participants without reduction in pain at 120 minutes after treatment	Treatment responders were defined as those with a reduction of pain from moderate to severe (>=4/10 on the NRS) at T0 to no to mild (<=3/10 on the NRS) at 120 minutes after treatment with either sumatriptan/naproxen or placebo	Participants without reduction in pain at 120 minutes after treatment	Participants without reduction in pain at 120 minutes after treatment	Treatment responders were defined as those with a reduction of pain from moderate to severe (>=4/10 on the NRS) at T0 to no to mild (<=3/10 on the NRS) at 120 minutes after treatment with either sumatriptan/naproxen or placebo
Measure Participants	17	17	17	17	17	17
Mean (95% Confidence Interval) [ug/mL]	0.71	0.89	0.28	0.84	1.00	0.02

8. Secondary Outcome

Title	Resistin
Description	serum resistin levels after treatment in responders and non responders
Time Frame	30 minutes after treatment, 60 minutes after treatment, 120 minutes after treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment Responders 120 Minutes After Treatment	Treatment Non Responders 120 Minutes After Treatment	Treatment Responders 30 Minutes After Treatment	Treatment Non-Responders 30 Minutes After Treatment	Treatment Non-Responders 60 Minutes After Treatment	Treatment Responders 60 Minutes After Treatment
Arm/Group Description	Treatment responders were defined as those with a reduction of pain from moderate to severe (>=4/10 on the NRS) at T0 to no to mild (<=3/10 on the NRS) at 120 minutes after treatment with either sumatriptan/naproxen or placebo	Participants without reduction in pain at 120 minutes after treatment	Treatment responders were defined as those with a reduction of pain from moderate to severe (>=4/10 on the NRS) at T0 to no to mild (<=3/10 on the NRS) at 120 minutes after treatment with either sumatriptan/naproxen or placebo	Participants without reduction in pain at 120 minutes after treatment	Participants without reduction in pain at 120 minutes after treatment	Treatment responders were defined as those with a reduction of pain from moderate to severe (>=4/10 on the NRS) at T0 to no to mild (<=3/10 on the NRS) at 120 minutes after treatment with either sumatriptan/naproxen or placebo
Measure Participants	17	17	17	17	17	17
Mean (95% Confidence Interval) [ug/mL]	-0.95	-0.97	-1	-0.88	-1.36	-0.79

Adverse Events

Arm/Group Title	Treximet		Sugar Pill
Arm/Group Description	sumatriptan/naproxen sodium: 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.		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.
All Cause Mortality
	Treximet		Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Treximet		Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/17 (0%)		0/17 (0%)
Other (Not Including Serious) Adverse Events
	Treximet		Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/17 (0%)		0/17 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.