Clinical Trial Details
— Status: Terminated
Administrative data
| NCT number |
NCT02753972 |
| Other study ID # |
HRRC#: 06-254 |
| Secondary ID |
|
| Status |
Terminated |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
August 2006 |
| Est. completion date |
October 2007 |
Study information
| Verified date |
March 2024 |
| Source |
University of New Mexico |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
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
