Can weight loss improve migraine headaches in obese women? Rationale and design of the Women's Health and Migraine (WHAM) randomized controlled trial

Dale S Bond, Kevin C O'Leary, J Graham Thomas, Richard B Lipton, George D Papandonatos, Julie Roth, Lucille Rathier, Richard Daniello, Rena R Wing, Dale S Bond, Kevin C O'Leary, J Graham Thomas, Richard B Lipton, George D Papandonatos, Julie Roth, Lucille Rathier, Richard Daniello, Rena R Wing

Abstract

Background: Research demonstrates a link between migraine and obesity. Obesity increases the risk of frequent migraines and is associated with migraine prevalence among reproductive-aged women. These findings are substantiated by several plausible mechanisms and emerging evidence of migraine improvements after surgical and non-surgical weight loss. However, no previous study has examined the effect of weight loss on migraine within a treatment-controlled framework. The WHAM trial is an RCT to test the efficacy of behavioral weight loss as a treatment for migraine.

Study design: Overweight/obese women (n=140; BMI=25.0-49.9 kg/m(2)) who meet international diagnostic criteria for migraine and record ≥3 migraines and 4-20 migraine days using a smartphone-based headache diary during a 4-week baseline period, will be randomly assigned to 4 months of either group-based behavioral weight loss (intervention) or migraine education (control). Intervention participants will be taught strategies to increase physical activity and consume fewer calories in order to lose weight. Control participants will receive general education on migraine symptoms/triggers and various treatment approaches. Both groups will use smartphones to record their headaches for 4 weeks at baseline, after the 16-week treatment period, and at the end of a 16-week follow-up period. Changes in weight and other potential physiological (inflammation), psychological (depression), and behavioral (diet and physical activity) mediators of the intervention effect will also be assessed.

Conclusion: The WHAM trial will evaluate the efficacy of a standardized behavioral weight loss intervention for reducing migraine frequency, and the extent to which weight loss and other potential mediators account for intervention effects.

Copyright © 2013 Elsevier Inc. All rights reserved.

Figures

Fig. 1. Hypothesized mediational pathways through which…
Fig. 1. Hypothesized mediational pathways through which the behavioral weight loss intervention contributes to reduction in frequency of migraine headaches
A. Primary mediator: weight loss We will test the hypothesis that greater weight loss mediates differences in reduction of migraine days between the behavioral weight loss (BWL) intervention and migraine education (ME) control groups, as depicted in Figure 1A above. Weight loss is identified as the primary mediator based on epidemiological research that demonstrates a relationship between obesity and increased migraine frequency [–8] and recent observational data indicating significant reductions in migraine frequency after both surgical and behavioral weight loss interventions [–22]. B. Exploratory mediators: Changes in inflammation, depression, and physical activity and dietary patterns. In exploratory mediational analyses depicted above in Figure 1B, we will first examine whether more favorable changes in physical activity and/or diet, adjusting for weight loss, mediate differences in reduction of migraine days between the BWL intervention and ME control groups. Physical activity and diet were identified as mediators given that increases in physical activity and decreases in caloric intake are primary targets of BWL interventions and are strong predictors of treatment success [–91]. Moreover both behaviors are related to reductions in migraine frequency and severity [–94]. We will next examine whether greater weight-loss associated reductions in inflammatory biomarkers and/or depression account for differences in reduction of migraine days between the BWL intervention and ME control groups. Inflammation was selected as a mediator because systemic inflammation is a pathophysiological process shared by migraine and obesity [17, 19], obesity-related inflammation is thought to contribute to higher migraine frequency via increased neurovascular inflammation and central sensitization [17], and reductions in inflammation as evidenced by lowered levels of C-reactive protein (CRP) and proinflammatory cytokines such as interleukin-6 (IL-6) occur after BWL interventions [–96]. Depression was chosen as a mediator because depression is comorbid to both obesity and migraine, increases risk for high headache frequency in obese migraineurs, and is reduced after BWL intervention [, –98].
Fig. 2. Study design and timeline of…
Fig. 2. Study design and timeline of study assessments and interventions
Participants will be randomized to receive behavioral weight loss intervention or migraine education for 16 weeks. Participants will complete a 4-week electronic migraine headache diary at pre- and post-treatment and after a 16-week non-intervention, weight maintenance period. Hypothesized mediators of the intervention effect including weight, inflammation, depression, and physical activity and dietary habits will be assessed prior to completion of the electronic headache diary at pre- and post-treatment. Weight will also be assessed at 16-week follow-up.
Figure 3
Figure 3
Example smartphone-based headache diary forms

References

    1. The International Classification of Headache Disorders. Cephalalgia. (2) 2004;24 (Suppl 1):9–160.
    1. Lipton RB, Bigal ME, Diamond M, Freitag F, Reed ML, Stewart WF. Migraine prevalence, disease burden, and the need for preventive therapy. Neurology. 2007;68:343–9.
    1. Buse D, Manack A, Serrano D, Reed M, Varon S, Turkel C, et al. Headache impact of chronic and episodic migraine: results from the American Migraine Prevalence and Prevention study. Headache. 2012;52:3–17.
    1. Hawkins K, Wang S, Rupnow M. Direct cost burden among insured US employees with migraine. Headache. 2008;48:553–63.
    1. Hu XH, Markson LE, Lipton RB, Stewart WF, Berger ML. Burden of migraine in the United States: disability and economic costs. Arch Intern Med. 1999;159:813–8.
    1. Bigal ME, Liberman JN, Lipton RB. Obesity and migraine: a population study. Neurology. 2006;66:545–50.
    1. Bigal ME, Lipton RB. Obesity is a risk factor for transformed migraine but not chronic tension-type headache. Neurology. 2006;67:252–7.
    1. Bigal ME, Tsang A, Loder E, Serrano D, Reed ML, Lipton RB. Body mass index and episodic headaches: a population-based study. Arch Intern Med. 2007;167:1964–70.
    1. Peterlin BL, Rosso AL, Rapoport AM, Scher AI. Obesity and Migraine: The Effect of Age, Gender and Adipose Tissue Distribution. Headache. 2009
    1. Vo M, Ainalem A, Qiu C, Peterlin BL, Aurora SK, Williams MA. Body Mass Index and Adult Weight Gain Among Reproductive Age Women With Migraine. Headache. 2011
    1. Yu S, Liu R, Yang X, Zhao G, Qiao X, Feng J, et al. Body mass index and migraine: a survey of the Chinese adult population. J Headache Pain. 2012;13:531–6.
    1. Ford ES, Li C, Pearson WS, Zhao G, Strine TW, Mokdad AH. Body mass index and headaches: findings from a national sample of US adults. Cephalalgia. 2008;28:1270–6.
    1. Keith SW, Wang C, Fontaine KR, Cowan CD, Allison DB. BMI and headache among women: results from 11 epidemiologic datasets. Obesity (Silver Spring) 2008;16:377–83.
    1. Winter AC, Berger K, Buring JE, Kurth T. Body mass index, migraine, migraine frequency and migraine features in women. Cephalalgia. 2009;29:269–78.
    1. Mattsson P. Migraine headache and obesity in women aged 40–74 years: a population-based study. Cephalalgia. 2007;27:877–80.
    1. Lipton RB, Bigal ME. The epidemiology of migraine. Am J Med. 2005;118 (Suppl 1):3S–10S.
    1. Bigal ME, Lipton RB, Holland PR, Goadsby PJ. Obesity, migraine, and chronic migraine: possible mechanisms of interaction. Neurology. 2007;68:1851–61.
    1. Peterlin BL, Rapoport AM, Kurth T. Migraine and Obesity: Epidemiology, Mechanisms, and Implications. Headache. 2009
    1. Bond DS, Roth J, Nash JM, Wing RR. Migraine and obesity: epidemiology, possible mechanisms and the potential role of weight loss treatment. Obes Rev. 2011;12:e362–71.
    1. Tietjen GE, Peterlin BL, Brandes JL, Hafeez F, Hutchinson S, Martin VT, et al. Depression and anxiety: effect on the migraine-obesity relationship. Headache. 2007;47:866–75.
    1. Bond DS, Vithiananthan S, Nash JM, Thomas JG, Wing RR. Improvement of migraine headaches in severely obese patients after bariatric surgery. Neurology. 2011;76:1135–8.
    1. Novack V, Fuchs L, Lantsberg L, Kama S, Lahoud U, Horev A, et al. Changes in headache frequency in premenopausal obese women with migraine after bariatric surgery: a case series. Cephalalgia. 2011;31:1336–42.
    1. Verrotti A, Agostinelli S, D’Egidio C, Di Fonzo A, Carotenuto M, Parisi P, et al. Impact of a weight loss program on migraine in obese adolescents. Eur J Neurol. 2012
    1. Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346:393–403.
    1. Wadden TA, West DS, Delahanty L, Jakicic J, Rejeski J, Williamson D, et al. The Look AHEAD study: a description of the lifestyle intervention and the evidence supporting it. Obesity (Silver Spring) 2006;14:737–52.
    1. Wing RR. Long-term effects of a lifestyle intervention on weight and cardiovascular risk factors in individuals with type 2 diabetes mellitus: four-year results of the Look AHEAD trial. Arch Intern Med. 2010;170:1566–75.
    1. The Diabetes Prevention Program (DPP): description of lifestyle intervention. Diabetes Care. 2002;25:2165–71.
    1. Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults--The Evidence Report. National Institutes of Health. Obes Res. 1998;6 (Suppl 2):51S–209S.
    1. Goodpaster BH, Delany JP, Otto AD, Kuller L, Vockley J, South-Paul JE, et al. Effects of diet and physical activity interventions on weight loss and cardiometabolic risk factors in severely obese adults: a randomized trial. JAMA. 2010;304:1795–802.
    1. Wu T, Gao X, Chen M, van Dam RM. Long-term effectiveness of diet-plus-exercise interventions vs. diet-only interventions for weight loss: a meta-analysis. Obes Rev. 2009;10:313–23.
    1. Donnelly JE, Blair SN, Jakicic JM, Manore MM, Rankin JW, Smith BK. American College of Sports Medicine Position Stand. Appropriate physical activity intervention strategies for weight loss and prevention of weight regain for adults. Med Sci Sports Exerc. 2009;41:459–71.
    1. Tudor-Locke C, Lutes L. Why do pedometers work?: a reflection upon the factors related to successfully increasing physical activity. Sports Med. 2009;39:981–93.
    1. Perri MG, Martin AD, Leermakers EA, Sears SF, Notelovitz M. Effects of group- versus home-based exercise in the treatment of obesity. J Consult Clin Psychol. 1997;65:278–85.
    1. DiPietro L, Williamson DF, Caspersen CJ, Eaker E. The descriptive epidemiology of selected physical activities and body weight among adults trying to lose weight: the Behavioral Risk Factor Surveillance System survey, 1989. Int J Obes Relat Metab Disord. 1993;17:69–76.
    1. Williams DM, Matthews CE, Rutt C, Napolitano MA, Marcus BH. Interventions to increase walking behavior. Med Sci Sports Exerc. 2008;40:S567–73.
    1. Stuart RB. Behavioral control of overeating. 1967. Obes Res. 1996;4:411–7.
    1. D’Zurilla TJ, Goldfried MR. Problem solving and behavior modification. J Abnorm Psychol. 1971;78:107–26.
    1. Wing RR, Jeffery RW. Benefits of recruiting participants with friends and increasing social support for weight loss and maintenance. J Consult Clin Psychol. 1999;67:132–8.
    1. Bandura ASK. The role of proximal intentions in self-regulation of refractory behavior. Cognitive Therapy and Research. 1977;1:177–93.
    1. Perri MG, Nezu AM, McKelvey WF, Shermer RL, Renjilian DA, Viegener BJ. Relapse prevention training and problem-solving therapy in the long-term management of obesity. J Consult Clin Psychol. 2001;69:722–6.
    1. Burke LE, Wang J, Sevick MA. Self-monitoring in weight loss: a systematic review of the literature. J Am Diet Assoc. 2011;111:92–102.
    1. Pi-Sunyer X, Blackburn G, Brancati FL, Bray GA, Bright R, Clark JM, et al. Reduction in weight and cardiovascular disease risk factors in individuals with type 2 diabetes: one-year results of the look AHEAD trial. Diabetes Care. 2007;30:1374–83.
    1. Subak LL, Wing R, West DS, Franklin F, Vittinghoff E, Creasman JM, et al. Weight loss to treat urinary incontinence in overweight and obese women. N Engl J Med. 2009;360:481–90.
    1. Stewart WF, Lipton RB, Dowson AJ, Sawyer J. Development and testing of the Migraine Disability Assessment (MIDAS) Questionnaire to assess headache-related disability. Neurology. 2001;56:S20–8.
    1. Kosinski M, Bayliss MS, Bjorner JB, Ware JE, Jr, Garber WH, Batenhorst A, et al. A six-item short-form survey for measuring headache impact: the HIT-6. Qual Life Res. 2003;12:963–74.
    1. Yang M, Rendas-Baum R, Varon SF, Kosinski M. Validation of the Headache Impact Test (HIT-6) across episodic and chronic migraine. Cephalalgia. 2011;31:357–67.
    1. Lipton RB, Bigal ME, Ashina S, Burstein R, Silberstein S, Reed ML, et al. Cutaneous allodynia in the migraine population. Ann Neurol. 2008;63:148–58.
    1. Bigal ME, Ashina S, Burstein R, Reed ML, Buse D, Serrano D, et al. Prevalence and characteristics of allodynia in headache sufferers: a population study. Neurology. 2008;70:1525–33.
    1. French DJ, Holroyd KA, Pinell C, Malinoski PT, O’Donnell F, Hill KR. Perceived self-efficacy and headache-related disability. Headache. 2000;40:647–56.
    1. Seng EK, Holroyd KA. Dynamics of changes in self-efficacy and locus of control expectancies in the behavioral and drug treatment of severe migraine. Ann Behav Med. 2010;40:235–47.
    1. Ray L, Lipton RB, Zimmerman ME, Katz MJ, Derby CA. Mechanisms of association between obesity and chronic pain in the elderly. Pain. 2011;152:53–9.
    1. Radloff L. The CES-D scale: a self-report depressive scale for research in the general population. J Appl Psychol Meas. 1977;1:385–401.
    1. Kroenke K, Spitzer RL, Williams JB, Monahan PO, Lowe B. Anxiety disorders in primary care: prevalence, impairment, comorbidity, and detection. Ann Intern Med. 2007;146:317–25.
    1. Lowe B, Decker O, Muller S, Brahler E, Schellberg D, Herzog W, et al. Validation and standardization of the Generalized Anxiety Disorder Screener (GAD-7) in the general population. Med Care. 2008;46:266–74.
    1. Cohen S, Kamarck T, Mermelstein R. A global measure of perceived stress. J Health Soc Behav. 1983;24:385–96.
    1. Houle T, Nash JM. Stress and headache chronification. Headache. 2008;48:40–4.
    1. Rasmussen BK, Olesen J. Migraine with aura and migraine without aura: an epidemiological study. Cephalalgia. 1992;12:221–8. discussion 186.
    1. Block JP, He Y, Zaslavsky AM, Ding L, Ayanian JZ. Psychosocial stress and change in weight among US adults. Am J Epidemiol. 2009;170:181–92.
    1. Pyykkonen AJ, Raikkonen K, Tuomi T, Eriksson JG, Groop L, Isomaa B. Stressful life events and the metabolic syndrome: the prevalence, prediction and prevention of diabetes (PPP)-Botnia Study. Diabetes Care. 2010;33:378–84.
    1. Johannsen DL, Calabro MA, Stewart J, Franke W, Rood JC, Welk GJ. Accuracy of armband monitors for measuring daily energy expenditure in healthy adults. Med Sci Sports Exerc. 2010;42:2134–40.
    1. Jakicic JM, Marcus M, Gallagher KI, Randall C, Thomas E, Goss FL, et al. Evaluation of the SenseWear Pro Armband to assess energy expenditure during exercise. Med Sci Sports Exerc. 2004;36:897–904.
    1. Ma Y, Olendzki BC, Pagoto SL, Hurley TG, Magner RP, Ockene IS, et al. Number of 24-hour diet recalls needed to estimate energy intake. Ann Epidemiol. 2009;19:553–9.
    1. Stunkard AJ, Waxman M. Accuracy of self-reports of food intake. J Am Diet Assoc. 1981;79:547–51.
    1. Buysse DJ, Reynolds CF, 3rd, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989;28:193–213.
    1. Foster GD, Sanders MH, Millman R, Zammit G, Borradaile KE, Newman AB, et al. Obstructive sleep apnea among obese patients with type 2 diabetes. Diabetes Care. 2009;32:1017–9.
    1. Scher AI, Stewart WF, Ricci JA, Lipton RB. Factors associated with the onset and remission of chronic daily headache in a population-based study. Pain. 2003;106:81–9.
    1. Foster GD, Borradaile KE, Sanders MH, Millman R, Zammit G, Newman AB, et al. A randomized study on the effect of weight loss on obstructive sleep apnea among obese patients with type 2 diabetes: the Sleep AHEAD study. Arch Intern Med. 2009;169:1619–26.
    1. Kallweit U, Hidalgo H, Uhl V, Sandor PS. Continuous positive airway pressure therapy is effective for migraines in sleep apnea syndrome. Neurology. 2011;76:1189–91.
    1. Roy J, Alderson D, Hogan JW, Tashima KT. Conditional inference methods for incomplete Poisson data with endogenous time-varying covariates: Emergency department use among HIV-infected women. J Am Stat Assoc. 2006;101:424–34.
    1. SAS Institute I. SAS/STAT 9.2: Changes and Enhancements. Cary, NC: SAS Institute, Inc; 2008.
    1. Xu S, Gargiullo P, Mullooly J, McClure D, Hambidge SJ, Glanz J. Fitting parametric and semi-parametric conditional poisson regression models with Cox’s Partial Likelihood in self-controlled case series and matched cohort series. J Data Sci. 2010;8:349–60.
    1. Holm S. A simple sequentially rejective multiple test procedure. Scandinavian Journal of Statistics. 1979;6:65–70.
    1. MacKinnon DP. Introduction to statistical mediation analysis. New York, NY: Lawrence Erlbaum Associates; 2008.
    1. Preacher KJ, Hayes AF. SPSS and SAS procedures for estimating indirect effects in simple mediation models. Behav Res Methods Instrum Comput. 2004;36:717–31.
    1. Preacher KJ, Hayes AF. Asymptotic and resampling strategies for assessing and comparing indirect effects in multiple mediator models. Behav Res Methods. 2008;40:879–91.
    1. Napolitano MA, Papandonatos GD, Lewis BA, Whiteley JA, Williams DM, King AC, et al. Mediators of physical activity behavior change: a multivariate approach. Health Psychol. 2008;27:409–18.
    1. Mohr DC, Spring B, Freedland KE, Beckner V, Arean P, Hollon SD, et al. The selection and design of control conditions for randomized controlled trials of psychological interventions. Psychother Psychosom. 2009;78:275–84.
    1. Holroyd KA, Cottrell CK, O’Donnell FJ, Cordingley GE, Drew JB, Carlson BW, et al. Effect of preventive (beta blocker) treatment, behavioural migraine management, or their combination on outcomes of optimised acute treatment in frequent migraine: randomised controlled trial. BMJ. 2010;341:c4871.
    1. Connelly M, Bickel J. An Electronic Daily Diary Process Study of Stress and Health Behavior Triggers off Primary Headaches in Children. J Pediatr Psychol. 2011
    1. Connelly M, Miller T, Gerry G, Bickel J. Electronic momentary assessment of weather changes as a trigger of headaches in children. Headache. 2010;50:779–89.
    1. Shiffman S, Stone AA, Hufford MR. Ecological momentary assessment. Annu Rev Clin Psychol. 2008;4:1–32.
    1. Stone AA, Shiffman S, Schwartz JE, Broderick JE, Hufford MR. Patient compliance with paper and electronic diaries. Control Clin Trials. 2003;24:182–99.
    1. Ware JE, Jr, Bjorner JB, Kosinski M. Practical implications of item response theory and computerized adaptive testing: a brief summary of ongoing studies of widely used headache impact scales. Med Care. 2000;38:II73–82.
    1. Varkey E, Hagen K, Zwart JA, Linde M. Physical activity and headache: results from the Nord-Trondelag Health Study (HUNT) Cephalalgia. 2008;28:1292–7.
    1. Milde-Busch A, Blaschek A, Borggrafe I, Heinen F, Straube A, von Kries R. Associations of diet and lifestyle with headache in high-school students: results from a cross-sectional study. Headache. 2010;50:1104–14.
    1. Shephard RJ. Limits to the measurement of habitual physical activity by questionnaires. Br J Sports Med. 2003;37:197–206. discussion.
    1. Thomas JG, Bond DS, Sarwer DB, Wing RR. Technology for behavioral assessment and intervention in bariatric surgery. Surg Obes Relat Dis. 2011;7:548–57.
    1. Nicholson R, Bigal M. Screening and behavioral management: obesity and weight management. Headache. 2008;48:51–7.
    1. Raynor HA, Jeffery RW, Tate DF, Wing RR. Relationship between changes in food group variety, dietary intake, and weight during obesity treatment. Int J Obes Relat Metab Disord. 2004;28:813–20.
    1. Wadden TA, West DS, Neiberg RH, Wing RR, Ryan DH, Johnson KC, et al. One-year weight losses in the Look AHEAD study: factors associated with success. Obesity (Silver Spring) 2009;17:713–22.
    1. Wadden TA, Neiberg RH, Wing RR, Clark JM, Delahanty LM, Hill JO, et al. Four-year weight losses in the Look AHEAD study: factors associated with long-term success. Obesity (Silver Spring) 2011;19:1987–98.
    1. Bic Z, Blix GG, Hopp HP, Leslie FM, Schell MJ. The influence of a low-fat diet on incidence and severity of migraine headaches. J Womens Health Gend Based Med. 1999;8:623–30.
    1. Varkey E, Cider A, Carlsson J, Linde M. Exercise as migraine prophylaxis: A randomized study using relaxation and topiramate as controls. Cephalalgia. 2011;31:1428–38.
    1. Narin SO, Pinar L, Erbas D, Ozturk V, Idiman F. The effects of exercise and exercise-related changes in blood nitric oxide level on migraine headache. Clin Rehabil. 2003;17:624–30.
    1. Hofso D, Nordstrand N, Johnson LK, Karlsen TI, Hager H, Jenssen T, et al. Obesity-related cardiovascular risk factors after weight loss: a clinical trial comparing gastric bypass surgery and intensive lifestyle intervention. Eur J Endocrinol. 2010;163:735–45.
    1. Esposito K, Pontillo A, Di Palo C, Giugliano G, Masella M, Marfella R, et al. Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial. JAMA. 2003;289:1799–804.
    1. Williamson DA, Rejeski J, Lang W, Van Dorsten B, Fabricatore AN, Toledo K. Impact of a weight management program on health-related quality of life in overweight adults with type 2 diabetes. Arch Intern Med. 2009;169:163–71.
    1. Faulconbridge LF, Wadden TA, Rubin RR, Wing RR, Walkup MP, Fabricatore AN, et al. One-Year Changes in Symptoms of Depression and Weight in Overweight/Obese Individuals With Type 2 Diabetes in the Look AHEAD Study. Obesity (Silver Spring) 2011

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa