| Conditions: |
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Weight Gain - Healthy Subjects - Obesity - Women |
| Purpose: |
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Background:
- Rates of obesity have increased dramatically in recent decades, and researchers are
investigating how changes in diets and physical activity have contributed to this increase.
To understand how weight might be controlled, it is important to learn what kinds of dietary
changes can affect hunger and might lower body weight. Essential fatty acids, for instance,
are an important part of a healthy diet, but researchers have not yet determined the ideal
amount of essential fatty acids that people should eat. By studying how different diets
affect body chemistry and hormone levels in women who are overweight or obese, researchers
hope to be able to determine better diets or treatments to help people reach and maintain an
optimum healthy weight.
Objectives:
- To examine how certain fats in the diet affect body metabolism, hormones, and weight
regulation.
Eligibility:
- Healthy women between 18 and 50 years of age who are overweight or obese (body mass index
between 25 and 35).
Design:
- This study has an initial screening visit and three phases. All participants will be
involved in the first two phases of the study, and some participants will be involved
in the third phase.
- Participants will be screened with a physical examination and medical history, in
addition to blood and urine tests and questionnaires about eating habits and other diet
factors.
- Phase 1: Participants will have three visits to the National Institutes of Health over
a 4-week period (some may have a 36-hour inpatient evaluation visit as well). At the
visits, participants will have blood and urine tests, complete questionnaires, and have
other tests including brain and body imaging studies. The 36-hour inpatient stay will
measure hormone and food metabolism. Participants will then be assigned to one of three
study diets.
- Phase 2: Participants will have a 12-week diet phase, with all foods supplied by the
study researchers. Participants will keep a daily log of food and beverage intake, and
will have three testing sessions with procedures similar to those performed in Phase 1.
The same participants who had the 36-hour inpatient stay will have another 36-hour
stay.
- Phase 3: Participants assigned to a particular study diet (one-third of all
participants) will be given the option of continuing the diet for an additional 36
weeks (9 months), with food consumption, monitoring, and testing procedures similar to
those performed in Phase 2....
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| Study Summary: |
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3.1 Objective
To evaluate the effects of lowering the dietary nutrient linoleic acid (LA) as a controlled
variable on: 1) tissue accretion of omega-6 and omega-3 highly unsaturated fatty acids
(HUFA); 2) bioactive endocannabinoids derived from the omega-6 HUFA arachidonic acid (AA);
3) insulin sensitivity; 4) satiety and hunger; and 5) body composition. Modifications in
dietary LA will be offset with reciprocal changes in the nutrient oleic acid (OA) to
maintain equivalency of calories and nutrients.
3.2 Study Population
Up to 180 overweight, but otherwise healthy pre-menopausal women volunteers (aged 18 through
50) with body mass index (BMI) between 25 and 35 kg/m(2), will be enrolled.
With the anticipated dropout rates described in Section 7.4, we anticipate that 84 of these
subjects will be randomized to study diets, and 64 subjects will complete the 12 week diet
phase.
3.3.1 Three Group Comparative Analysis
A total of 84 subjects will be randomized to one of 3 healthy and nutritionally complete
diets that differ only in the fatty acid composition of added visible oils. All foods will
be provided through the NIH metabolic kitchen, with subjects visiting the kitchen daily
Monday through Friday to obtain foods. Each Friday, subjects will carry home foods packed
for their weekend meals. Baseline testing battery will include: 1) blood composition of
omega-6 and omega-3 HUFA; 2) endocannabinoid, eicosanoid, and docosanoid derivatives of
omega-6 and omega-3 HUFA; 3) insulin function assessment; 4) body composition assessment; 4)
functional satiety assessment; and 5) self-reported measures of satiety, hunger and
affective states. The full baseline testing battery will be repeated after 84 days of
randomized treatment. An abbreviated testing battery will be performed after 28 and 56 days
of randomized treatment.
A subset of participants will undergo additional inpatient testing in the 24-hour metabolic
chamber as described in Section 3.3.2. The remaining subjects will remain ambulatory
throughout the study. Participants will be advised to continue their usual medical care and
medications throughout the study.
3.3.2 24-Hour Metabolic Suite Study
A subset of 8 participants in each of the 3 groups will undergo the usual testing battery
and additional metabolic testing in the metabolic suite at 0, 28, and 84 days. The
additional testing will include pre- and post-prandial endocrine hormone assessment.
3.3.3 36-Week Continuation (Gradient Dose Replacement) Sub Study
At completion of the 84 day (12 week) study, participants in the low LA group (Group B) will
have the option of continuing their study diets for another 252 days (36 weeks). Continuing
subjects will consume be randomized to either: 1) the same low LA (1 en%) diet.; or 2) the
same baseline diet with a graded dose escalation of LA, with the addition of 1 en% of LA
every 6 weeks. In this manner, LA will increase incrementally from 1 en% to 8 en% over the
36 week period. During the continuation phase, the abbreviated testing battery will be
completed after 6, 12, 18, 24 and 30 weeks, and the full testing battery will be repeated
after 36 weeks.
3.4 Outcome Measures
3.4A Primary Dependent Variables
The primary outcomes will be the proportion of omega-6 HUFA in total HUFA (%omega-6 in HUFA)
and two endocannabinoids derived from omega-6 AA, 2-Arachidonoylglycerol (2-AG) and
N-Arachidonoylethanolamine (Anandamide or AEA).
3.4B Secondary Dependent Variables
Secondary outcome measures will include blood concentrations of the omega-6 HUFA Arachidonic
Acid (AA); the omega-3 HUFA Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA); the
rates of change in %omega-6 in HUFA, AA, EPA, DHA, 2-AG and AEA over time; adipose and
muscle tissue fatty acid composition; endocrine hormones; gene expression profiles;
psychometrics; functional satiety; 24-hr energy metabolism and substrate utilization; and
body composition, as follows: Omega-6 and omega-3 HUFA and total fat content will be
measured in adipose and muscle tissue biopsies. Other endocannabinoid, eicosanoid and
docosanoid derivatives of omega-6 and omega-3 HUFA will be measured in plasma via mass
spectrometry. Endocrine hormones will be measured in fasting and postprandial states in the
24-hour metabolic suite.
Psychometric outcomes will include self-reported measures of satiety and affective states.
Functional satiety will be assessed via buffet-style food array testing. Body composition
outcomes will include DEXA, 3T MRI, anthropometric measurements and bioelectrical impedance.
Genotyping will also be performed to assess for interactions between selected gene variants
and effects of the intervention.
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| Criteria: |
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- INCLUSION CRITERIA:
Subjects will be overweight, but otherwise healthy, pre-menopausal ambulatory volunteers
aged 18 to 50.
To be eligible for this research study, participants must:
- Be between 18 and 50 years of age.
- Have regular menstrual cycles.
- Be willing to use an effective method of birth control such as hormonal
contraception, intrauterine device, barrier methods combined with spermicide, or
surgical sterilization.
- Have a body mass index of 25 to 35 kg/m(2).
- Be otherwise healthy as determined by history, medical examination and laboratory
tests.
- Be able to come to the NIH Clinical Center every weekday for 3 months.
- Be able to understand the consent form, and provide informed written consent.
EXCLUSION CRITERIA:
Participants are not eligible for this research study if they:
- Have been pregnant or have breast fed within the last 2 years.
- Work, or have an immediate family member who works, with a study investigator.
Immediate family is defined as a spouse, parent, child or sibling, whether biological
or legally adopted.
- Are HIV positive.
- Have any current, unstable medical conditions including respiratory insufficiency
requiring oxygen therapy; cardiac ischemia; cardiac or hepatic failure; or acute
neurological illness as assessed by history and physical exam.
- Have evidence of diseases that may influence metabolism (e.g. overt diabetes
mellitus, thyroid disease, cancer)
- Have any current or past history of eating disorders such as binge eating or anorexia
nervosa.
- Have had weight loss (bariatric) surgery.
- Have gained or lost more than 3% of your current weight in the past 3 months.
- Exercise strenuously, like running, swimming, or basketball, 4 or more times per
week.
- Are planning to begin a strenuous exercise program in the next 4 months.
- Take supplements that contain omega-6 or omega-3 fatty acids (e.g. fish, cod liver,
borage, evening primrose oils)
- Have significant dietary limitations (e.g. multiple food allergies/intolerances,
vegan diet) or special dietary requirements that are difficult to accommodate with
study diets
- Have significant claustrophobia that would preclude study tests.
- Have a history of alcohol or substance abuse or dependence in the past 5 years.
- Drink more than 2 alcoholic beverages per day, on average, or 6 drinks per sitting in
the past year. Participants may drink up to one alcoholic beverage per day during the
study.
- Used marijuana, amphetamines, cocaine, or heroin even once over the last year.
Participants may not use marijuana, amphetamines, cocaine, or heroin during the
study.
- Have smoked 2 or more cigarettes per week, on average, over the past year.
- Participants may not use tobacco products during the study.
- Eat fish 3 or more times per week on average.
- Have a known bleeding disorder.
- Take medications or supplements that may interfere with this study by altering energy
metabolism, nutrient absorption, or food intake. Regular use of the following
compounds warrants exclusion: medications for the management of diabetes (Type 1 or
2), typical and atypical antipsychotics, thyroid medications, glucocorticoids,
orlistat, decongestants, anti-histamines, and medications for cardiac conditions (e.g
beta blockers), attention disorders (e.g. amphetamine derivatives), blood lipid
disorders (e.g. statins, fibrates), and hypertension (e.g. thiazide diuretics), as
well as certain anti-depressants (e.g. tricyclics), and supplements that impact
energy metabolism, such as ephedrine.
- Regularly take an anticoagulant medication, such as warfarin or aspirin.
- Have a pacemaker, brain stimulator, or other implanted electrical device, permanent
eyeliner, metallic prosthesis (including metal pins and rods, heart valves, and
cochlear implants) that would preclude MRI scans.
- Are currently participating in any other clinical research studies that include blood
draws or other procedures.
- Have a serum FSH level greater than 20 units per liter
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| NCT ID: |
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NCT01251887 |
| Primary Contact: |
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Principal Investigator
Christopher E Ramsden, M.D.
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Christopher E Ramsden, M.D.
Phone: (301) 496-7630
Email: ramsdence@mail.nih.gov
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| Backup Contact: |
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N/A |
| Location Contact: |
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Bethesda, Maryland 20892
United States
For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)
Phone: 800-411-1222
Email: prpl@mail.cc.nih.gov
Site Status: Recruiting |