Ictal Adiponectin Levels in Episodic Migraineurs: A Randomized Pilot Trial

Authors


  • Conflict of Interest: B. Lee Peterlin: This study was funded by an investigator-initiated grant to Dr. Peterlin through GlaxoSmithKline (GSK). In the past 2 years, Dr. Peterlin has not served as a consultant or speaker with any pharmaceutical company. Dr. Peterlin receives salary support through a mentored patient-oriented career research award (K23 10896737) from the National Institute of Neurological Disorders and Stroke and is an associate editor at the journal, Headache; Gretchen Tietjen: Dr. Tietjen has received research support from GSK and has been on the advisory board of MAP Pharmaceuticals. Dr. Tietjen is an associate editor at the journal, Headache. She owns common stock in J&J and Stryker; Barbara A. Gower: No disclosures; Thomas A. Ward: Dr. Ward has received research grant support from GSK and is a consultant with Cowen and Co. Dr. Ward is the Editor-in-Chief of Headache; Stewart J. Tepper: Dr. Tepper has received research support (no personal compensation from ATI [active], Boston Scientific [active], BristolMyerSquibb [active], DepoMed [active], GSK [active], MAP [active], Merck [active], NuPathe [active], OptiNose [active], and Zogenix [active]). He has worked as a consultant for Allergan (active), ATI (active), GSK in the past, Helsinn in the past, MAP (active), Merck in the past, Nautilus (active), NuPathe (active), and Zogenix (active). He as served as a speaker for Allergan (active), ATI (active), GSK in the past, Merck in the past, Nautilus (active), and Zogenix (active). He has served as an adviser to Allergan (active), ATI (active), GSK in the past, Merck in the past, MAP (active), Nautilus (active), NuPathe (active), Pfizer (active), USWorldMeds (active), and Zogenix (active). He has stock options in ATI. He receives royalties from University of Mississippi Press, Peoples Publishing House of Peking, and Springer. Dr. Tepper is an associate editor at the journal, Headache, and Editor-in-Chief of Headache Currents; Linda W. White: No disclosures; Paul D. Dash: Dr. Dash has served as speaker for Teva Pharmaceuticals Industries; Edward R. Hammond: No disclosures; Jennifer Haythornthwaite: No disclosures.
  • Study Funding: Investigator-initiated grant to Dr. Peterlin through GlaxoSmithKline and an NINDS contract, K23-10896737.
  • Clinical Trials registration number: NCT01138150 (ClinicalTrials.gov).

Address all correspondence to B.L. Peterlin, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA, email: lpeterlin@jhmi.edu

Abstract

Objective

To assess ictal adiponectin (ADP) levels before and after acute abortive treatment in women episodic migraineurs.

Methods

Peripheral blood specimens were collected from women episodic migraineurs before and after acute abortive treatment with sumatriptan/naproxen sodium vs placebo. Univariate and multivariate models were utilized to examine the relationship between serum total ADP (T-ADP), ADP oligomers (high molecular weight [HMW], middle molecular weight, and low molecular weight [LMW]-ADP), and ADP ratio levels and pain severity. Paired t-tests and random intercept longitudinal models were utilized to assess the mean changes in T-ADP, ADP oligomers, and ratios over time in treatment responders and nonresponders.

Results

Twenty participants (11 responders, 9 nonresponders) have been studied to date. In all participants, increases in the HMW : LMW ADP ratio were associated with an increase in pain severity. For every 1 point increase in the HMW : LMW ratio, pain severity increased by 0.22 (Confidence Interval [CI]: 0.07, 0.37; P = .004). In contrast, for every 0.25 μg/mL increase in LMW-ADP, pain severity decreased by 0.20 (CI: −0.41, −0.002; P = .047). In treatment responders, T-ADP levels were reduced at 30 minutes (12.52 ± 3.4; P = .03), 60 minutes (12.32 ± 3.2; P = .017), and 120 minutes (12.65 ± 3.2; P = .016) after treatment as compared with onset (13.48 ± 3.8). Additionally, in responders, the HMW : LMW ratio level was greater at pain onset (3.70 ± 1.9 μg/mL) as compared with nonresponders (2.29 ± 0.71 μg/mL), P = .050. Responders also showed a decrease in the HMW : LMW ratio at 60 minutes (2.37 ± 1.1; P = .002) and 120 minutes (2.76 ± 1.4; P = .02) after treatment as compared with onset (3.70 ± 1.9). These changes in responders remained significant after adjusting for covariates, including measured body mass index (m-BMI). Although nonresponders showed no significant changes in unadjusted T-ADP or ADP oligomer or ratio levels, the HMW : LMW ratio was increased in nonresponders after adjustments (P = .025).

Conclusion

In this pilot study of women episodic migraineurs, the HMW : LMW ADP ratio level was associated with migraine severity and predictive of acute treatment response. ADP and the HMW : LMW ratio of ADP represent potential novel biomarkers and drug targets for episodic migraine.

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