Mindful Eating and Living for Obese Women
Condition: Obesity
Study type: Interventional

Summary: 
      Background: Mindfulness-based interventions may be effective in reducing the stress that may
      increase both obesity and inflammation.

      Purpose: The purpose of this study was to examine the effects of a mindful eating
      intervention on weight loss and health-related outcomes.

      Methods: Thirty-six obese, postmenopausal women were randomized to a six-week Mindful Eating
      and Living (MEAL) intervention or an active control group (CONT) consisting of nutritional
      counseling, goal setting, and group support. Weight, body mass index (BMI), waist-hip ratio
      (WHR), binge eating, interleukin-6 (IL-6) and C-reactive protein (CRP) were assessed at
      baseline and four follow-up periods up to one year.

      Results: Multilevel analyses showed that the MEAL group had reductions in weight, BMI, WHR,
      binge eating, IL-6, and CRP; the CONT group had reductions in weight, BMI, and binge eating.
      The reductions in binge eating, IL-6, and CRP were greater for the MEAL as compared with the
      CONT group.

      Conclusions: This study suggests that a mindfulness-based eating intervention may promote
      weight loss and reduce a variety of health-related risk factors in post-menopausal women who
      are obese.
    

Detailed description: 
      Hypothesis A brief mindfulness-based educational program specifically designed for obese
      individuals will enable them to gain mastery over previously automatic eating and activity
      habits and will be associated with enhanced mood, decreased inflammation, improved metabolic
      markers and weight control.

      Specific Aims

        1. To determine if a mindfulness-based educational program for obese persons (BMI ≥30)
           seeking to gain more control over eating and lifestyle result in significant improvement
           in BMI compared to a control group.

        2. To determine if a mindfulness-based educational program for obese persons seeking to
           gain more control over eating and lifestyle result in significant improvements in
           insulin resistance and other metabolic and physiologic parameters.

           EXPERIMENTAL DESIGN AND METHODS

           The final design of this study will be influenced by the results of the pilot study
           entitled Mindful Eating and Living I (MEAL I), which is currently underway. After
           completing the analysis of data from MEAL I, 50 post-menopausal women between the ages
           of 55 and 70 with BMI ≥30 kg/m2 will be recruited and screened to allow for possible
           screen failures. The goal is to enroll a group of 40 participants (n=20 control, n=20
           intervention).

           Randomization Study subjects will be randomized to treatment or control group and then
           further to an outpatient or inpatient admission subset. Randomization will be determined
           based on a randomization code devised by the University of New Mexico General Clinical
           Research Center (GCRC) statistician, and this randomization process will be administered
           by a GCRC staff person such that Drs. Sloan and Colleran, the investigators involved in
           the biological aspects of the study, will be blinded to the randomization.

           Enrolled subjects will be randomized as follows. Twenty will be randomized to the
           treatment group and 20 will be randomized to the control group. Those in the treatment
           group will receive counseling by the GCRC dietician as well as mindfulness training via
           the mindfulness curriculum developed during the MEAL 1 pilot study. Those in the control
           group will receive counseling by the GCRC dietician and monthly group check-in sessions.
           All subjects will have four GCRC visits to evaluate metabolic and physiologic parameters
           and to complete psychometric questionnaires.

           In-patient and Out-patient GCRC subsets Of the 40 enrolled subjects, 24 will be randomly
           assigned to a subset of patients who will be admitted for overnight stays in order to
           test insulin resistance parameters and to monitor nocturnal blood pressure. The
           remaining 16 subjects will have GCRC outpatient visits only. The rationale for an
           in-patient subset is logistical. Our protocol calls for patients to be admitted for
           baseline evaluation at a uniform time preceding the mindfulness intervention, and then
           at three later time points. All patients need to be evaluated as close to the same time
           as possible, as they are going through the intervention according to the same schedule.
           It is not logistically possible to admit 40 patients for overnight stays within a 10-14
           day interval at four different time periods. Admitting a subset of 24 patients for
           overnight stay allows an adequate sample size to measure insulin resistance. The
           biological markers being measured require a larger sample size to show statistical
           significance, and this larger sample size can be achieved without inpatient stays.

           Screening Subjects will be screened in the outpatient GCRC. Screening procedures will
           include thyroid stimulating hormone and late night salivary cortisol to rule out
           secondary causes of obesity and a basic metabolic panel to rule out other untreated
           medical conditions. Other screening tests will include a history and physical, to
           ascertain ability to initiate an exercise program. As part of the physical exam, a mini
           mental status exam will be performed to screen for cognitive impairment that would
           preclude them from participating in the mindfulness training curriculum.

           Study Design All subjects will undergo an initial GCRC visit, which will be outpatient
           or inpatient based on their subset assignment. At this first visit, medical evaluation,
           psychometric questionnaire administration and laboratory evaluation will occur as
           detailed below. Because fasting is required for the lab draws, the outpatient subjects
           will then be given a snack or meal by the GCRC dietician. Subjects will then meet with
           the GCRC dietician for a one-hour counseling session on weight loss.

           Those subjects in the inpatient subset will not visit the out-patient GCRC. Instead,
           they will be admitted for an observed overnight fast followed by an oral glucose
           tolerance test and will also undergo frequent blood pressure monitoring. During this
           admission, the same information obtained from the out-patient subset of subjects will
           also be obtained, and just as with the out-patient subset, these subjects will have a
           one-hour counseling session with the GCRC dietician. These dietician sessions are
           modeled after standard of care and include education about the food pyramid, food
           choices, activity monitoring, food diary and determination of a caloric goal and weight
           goal.

           After the first GCRC visit, subjects randomized to the treatment group (n=20) will begin
           a 6-week two-hour course on mindful eating entitled Mindful Eating & Living (MEAL). MEAL
           is a mindfulness training program which is designed specifically for obese individuals.
           MEAL teaches skills which can lead to increased awareness of eating, emotions, and
           judgment. Also included is information about activity and nutrition. The goal of
           mindfulness training is to allow people to cultivate awareness of their behaviors and
           provide themselves with choices, resulting in less bingeing or overeating, as well as
           increased sense of control, improved mood, and eventually, reduced weight. MEAL is a
           6-week curriculum, taught in weekly sessions of 2-hours each to a group of 20 people.
           Specific exercises include group discussion, mindfulness meditation, and group eating
           exercises. Participants use written materials and CD's at home on a daily basis. At the
           completion of the course, treatment subjects will then attend monthly refresher
           sessions.

           Subjects randomized to the control group will not undergo mindfulness training. In order
           to provide a socially supportive environment similar to that experienced by the
           treatment subjects, monthly check-in sessions will be conducted for the control
           subjects. At these sessions, subjects will be invited to check-in about their
           experiences with weight loss efforts including food choices, activity levels and caloric
           goals. The first check-in session will occur during week 1 of the treatment group's
           mindfulness course, the second during week 6 of the mindfulness course, after which
           monthly sessions will be held during the same weeks as the mindfulness refresher
           sessions.

           All subjects will undergo three additional outpatient or inpatient GCRC visits: #2) at
           the time of completion of the 6-week mindfulness training, #3) at the time four weeks
           after the final refresher course and #4) at the time three months after the final
           refresher course. The subjects of both the control and treatment groups will undergo
           GCRC visits during the same two-week period. All measures obtained at the first visit
           will be repeated. All subjects will have one-hour meetings with the GCRC dietician for
           weight loss counseling at each visit. The purpose of these GCRC visits or admissions
           will be to determine the immediate effects, short-term effects and long-term effects of
           the intervention on metabolic, inflammatory, and adipocytokine parameters. Out-patient
           subjects will be given their questionnaires in advance so they can complete them at
           their convenience and decrease the time required for their out-patient visits.

           Demographics data will be obtained at baseline. The following data will be obtained at
           baseline and at the three subsequent GCRC inpatient or outpatient visits: medical
           history, medication profile, smoking status, vital signs, body mass index (BMI),
           waist/hip measurements, bioelectrical impedance analysis (BIA), dual-energy X-ray
           absorptiometry (BXA), Neuroticism (Benet-Martinez), Perceived Stress (Cohen),
           Psychological Well-being Scale (Ryff), Resilience (Connor), Trait Meta-Mood Scale
           (Salovey), Physical Symptoms (Moos), Positive and Negative Affect (Watson), Spirituality
           and Religion (Fetzer), Kentucky Inventory of Mindfulness Skills (Baer), Freiburg
           Mindfulness Inventory (FMI; Buchheld), Beck Depression Inventory (Beck), Beck Anxiety
           Inventory (Beck), Binge Eating Scale (Gormally), Eating Inventory (Stunkard). At the
           post-mindfulness training visits, a meditation log will be collected from the treatment
           group subjects (attached). Psychometric data will be analyzed in Logan Hall of UNM's
           main campus.

           BIOLOGICAL MEASURES

           The following biological data will be obtained from blood samples, totaling
           approximately two teaspoons from each patient. Each of the following measures will be
           obtained at baseline and then at three additional time points as previously described.

           Insulin Sensitivity:

           Obesity is highly correlated with insulin resistance. Similarly, weight loss improves
           insulin sensitivity.30 Fasting glucose and insulin concentrations can be used to
           estimate the severity of insulin resistance (the HOMA model).41 A second validated
           measure of insulin resistance is the insulin resistance index (IRIp) which uses the
           formula: peak of blood glucose after oral glucose load x plasma insulin level/10.56 For
           this study subjects will fast for 12 hours glucose and insulin will be Measured at
           baseline (HOMA) and at 120 minutes (IRIp). We anticipate that MEAL will lead to
           significant improvements in insulin sensitivity. Literature review reveals that
           identifying a 40% decrease in HOMA-IR, given a large effect size, requires a sample size
           of 24, with 12 in each group.33,34 To see a 20% decrease in IRIp, given its medium to
           large effect size, requires a sample size of greater than 24.56 Nevertheless,
           identifying trends in IRIp is valuable. Furthermore, it is difficult to predict the
           change in insulin resistance we might see as a result of MEAL, as published studies
           involving drug and surgical interventions are poor comparisons.

           Fasting lipid profile:

           Along with insulin resistance, obesity is associated with a specific dyslipidemia
           including hypertriglyceridemia, low high-density lipoprotein (HDL) cholesterol and small
           dense and oxidized low-density lipoprotein (LDL) cholesterol.42-44 Weight reduction
           leads to significant improvements in hypertriglyceridemia.30 We anticipate that
           mindfulness will similarly improve lipid profiles. In order to see a statistically
           significant reduction in triglyceride levels of approximately 30%, given the medium to
           large effect sizes seen in the literature, requires a sample size of 40 with 20 in each
           group.33,34

           Adiponectin:

           Adiponectin is an adipose-derived protein that negatively correlates with increasing
           adiposity, insulin resistance, inflammatory mediators and cardiovascular disease. 31-33,
           45 Recently, a significant increase in adiponectin levels was seen in obese women
           following gastric bypass surgery, resulting in improvements in insulin sensitivity.33 A
           thorough literature search has revealed that the effects of mindfulness practice on
           adipocytokine levels have not yet been investigated. The MEAL study hypothesizes that
           mindfulness practice will be associated with an increase in adiponectin related to
           predicted weight loss. While the MEAL intervention is different from the diet and
           surgical interventions currently cited in the literature, we predict that our sample
           size of 40 will be adequate to identify a statistically significant increase in
           adiponectin of approximately 50%, given the medium to large effect size seen in the
           literature.33,40

           Interleukin (IL)-6, tumor necrosis factor-alpha (TNF- α), highly sensitive CRP
           (C-reactive protein):

           CRP is a major marker of inflammation. Its production by the liver is stimulated by a
           network of adipocytokines including IL-6 and TNF- α.33, 35, 36 Type 2 diabetes has been
           shown to be preceded by a state of sub-clinical inflammation.35 Additionally, The
           European Prospective Investigation into Cancer and Nutrition (EPIC) Potsdam Study showed
           that increased levels of IL-6 independently predicted the risk of type 2 diabetes, and
           that a combined elevation of IL-6 and TNF-α was also associated with increased risk.35
           Weight loss has been shown to induce a significant decrease in CRP and IL-6 and is
           associated with an improvement in insulin sensitivity.34 As well, a one-year
           multidisciplinary weight reduction program showed a decrease in IL-6 as well as TNF-α.37
           MEAL thus proposes that mindfulness-associated weight reduction will be associated with
           a decrease in IL-6, TNF- α and high sensitive CRP, which will further be associated with
           improved insulin sensitivity as estimated by fasting insulin and fasting glucose.

           A linear correlation between IL-6 and age has been established with an increase of 0.016
           pg/ml per year of life.47 This has not been found to be true for CRP. Previous studies
           show a 40-50% decrease in IL-6 and CRP with weight loss and display medium to large
           effect sizes.33,35 The effect size for TNF- α is much smaller.33,35 Thus, we predict
           that we will be able to identify a statistically significant decrease in IL-6 and CRP
           with a sample size of 40, while it will be unlikely that our TNF- α results will reach
           significance. Nevertheless, TNF- α is a central player in the adipocytokine cascade, and
           identifying trends in the relationships between TNF- α and the other markers remains a
           valuable endeavor. The normal increase of IL-6 with age will be accounted for in our
           analysis by entering age as a covariate.

           Plasminogen activator inhibitor type 1 (PAI-1):

           PAI-1 is an adipocytokine that negatively regulates fibrinolysis thus increasing
           thrombus formation. Its connection to cardiovascular disease, insulin resistance and
           type 2 diabetes has been previously established.38,39 Weight loss is associated with a
           decrease in PAI-1.29 Recently, the Health, Aging and Body Composition Study showed PAI-1
           to be independently associated with incident diabetes, and this association did not vary
           by sex or race.40 We hypothesize that PAI-1 levels will decrease with mindfulness
           practice and will be associated with improved insulin sensitivity. To see a decrease of
           30% in PAI-1 levels, given the medium to large effect sizes seen in the literature,
           requires a sample size of at least 40.40

           Cortisol States of glucocorticoid excess are known to be associated with insulin
           resistance and increased cardiovascular risk. Cortisol production has an
           adrenocorticotropic hormone (ACTH) dependent circadian rhythm with peak levels in the
           early morning and a nadir at night. ACTH and cortisol are secreted independent of
           circadian rhythm in response to physical and psychological stress.51 A previous study
           examining the transcendental meditation and cardiovascular risk revealed decreased
           cortisol levels.8 A study that has not yet been published by Waters et al hypothesizes
           that cortisol rhythmicity and response to meals is altered in obesity.57 We hypothesize
           that mindfulness training will result in decreased late night salivary cortisol levels
           and decreased serum cortisol levels in response to a glucose challenge.

           The following anthropometric and physiologic parameters will be obtained:

           Body Mass Index The Primary outcome will be a change in body mass index (BMI).
           Preliminary statistical analysis reveals that to show a statistically significant
           decrease in BMI of 1.25 points, given the large effect size, requires a sample size of
           24 subjects, 12 in each group, to achieve 80% power with an alpha of 0.05. Our sample
           size of 40 is adequate to determine if there is a significant improvement in BMI. BMI
           will be measured and recorded at each study visit.

           Bioelectrical Impedance Analysis Bioelectrical impedance analysis (BIA) is a tool to
           measure total body fat mass.52 While our sample size is not adequate to measure
           significant changes in total body fat, previous experience has demonstrated that for
           publication in peer reviewed journals, multiple anthropometric measurements are
           beneficial even if they do not change significantly. As this test if fairly ease to
           perform and of no risk to subjects we propose to include it in our study design.

           Dual Energy X-ray Absorptiometry Dual energy x-ray absorptiometry (DEXA) is a method to
           measure body composition which has superior accuracy over other methods such as BIA or
           BMI.52,53 DEXA also has the capacity to measure fat in different compartments including
           central and peripheral. Given the small effect size seen in previous studies in
           measuring percent body fat, our sample size may be only adequate enough to show a trend
           in changes in this measure. Of equal importance, however, is change in body fat
           distribution. Abdominal adiposity is known to be a strong predictor of Insulin
           resistance.54 We therefore hypothesize that mindfulness training will result in a
           decreased amount of abdominal compared to peripheral adiposity.

           Waist to Hip Ratio Numerous studies have demonstrated that increases waist hip ratios
           represent a significant risk for metabolic syndrome and cardiovascular disease (CVD),
           independent of BMI. While our sample size is not adequate to measure significant changes
           in total body fat, previous experience has demonstrated that for publication in peer
           reviewed journals, multiple anthropometric measurements are beneficial even if they do
           not change significantly. As this test if fairly ease to perform and of no risk to
           subjects we propose to include it in our study design.

           Nocturnal blood pressure dip:

           Most individuals exhibit circadian variation in blood pressure with decreased night-time
           blood pressure.47 Previous studies have shown that in patients with or without
           hypertension, a diminished nocturnal decline in blood pressure is a risk for
           cardiovascular mortality and is associated with elevated levels of inflammatory markers
           including PAI-1.48, 49 To determine the effect of mindfulness training on nocturnal dip
           in blood pressure, we will admit a subset of patients for overnight stays and will
           monitor their blood pressure via a 24-hour blood pressure monitor. Beginning at
           approximately 7 pm, blood pressure will be measured every 15 minutes. During sleeping
           hours, blood pressure will be measured every 30 minutes. Subjects will then go home with
           the blood pressure monitor and will return it to the GCRC that evening at approximately
           7 pm.55 In 2005, Schneider et al published a study showing that transcendental
           meditation decreased levels of hypertension in African Americans with hypertension over
           a one year time period.9 We, therefore, hypothesize that the nocturnal blood pressure
           dip will be lower in the treatment group after mindfulness training than in the control
           group.

           SCREENING LABS

           Thyroid stimulating hormone (TSH):

           Hypothyroidism is a cause of secondary obesity, while hyperthyroidism is a cause of
           secondary weight loss. While the only exclusionary criteria for this pilot study is a
           BMI <35, information on participants' thyroid status is important in the ultimate trend
           analysis of our pilot data.

           Salivary late night cortisol:

           Cushing's syndrome is as an etiology of obesity that alters metabolism and prevents
           weight loss. Any person with an elevated salivary late night cortisol level will be
           excluded from the study.

           INPATIENT VISIT PROCEDURES/TIME LINE FOR 24 TOTAL SUBJECTS 1800 hrs Admission 1800 hrs
           standard meal 1800-2200 hrs blood pressure measurements every 30 minutes 2000 hrs begin
           overnight fast 2200-0800 hrs blood pressure measurements every 60 minutes 0800-0900 hrs
           blood pressure measurements every 5 minutes 0800 hrs BIA, H/W ratio, BXA 0830 hrs blood
           draw 1 (glucose, insulin, cortisol, adiponectin, PAI-1, hsCRP, lipids, IL-6, TNF-alpha)
           0835 hrs 75-gram glucola drink 0835-1030 hrs complete psychometric surveys, diet
           counseling. 1035 hrs blood draw 2 (glucose, insulin, cortisol) 1045 hrs standardized
           breakfast 1130 hrs discharge
    

Intervention name(s): Mindful Eating and Living; Active Weight Loss Control
Intervention type(s): Behavioral; Behavioral
Intervention description(s): 8 week mindfulness skills intervention; 8 week active weight loss control group
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Health Services Research