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Weight GainNCT01251887

Dietary Essential Fatty Acid Regulation of Omega-3 HUFA Metabolism; Satiety and Body Composition

A study testing Linoleic Acid, Docosahexaenoic Acid and Eicosapentaenoic Acid in people with Weight Gain and Healthy Subjects, run by National Institute on Alcohol Abuse and Alcoholism (NIAAA) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 50 years, women onlyHealthy volunteers can take part
Conditions the study is for
Weight Gain, Healthy Subjects, Obesity
What is being tested?
Linoleic Acid, Docosahexaenoic Acid and Eicosapentaenoic Acid
Could I receive a placebo?
No, everyone receives an active treatment
How many people
85 participants
Where
1 siteUnited States
Study dates
12 Nov 2010to 25 Jul 2018
Phase
Interventional
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 50 years
  • Women only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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).
Show all 9Show fewer
  • 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.

Who cannot join

  • 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)
Show all 26Show fewer
  • 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 follicle-stimulating hormone (FSH) level greater than 20 units per liter

Trial locations and contacts

1 site in 1 country.

United States1 site
  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: Dietary Linoleic Acid Regulation of Omega-3 HUFA Metabolism: Satiety and Body Composition Among Overweight Female Subjects

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.
Read more

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. At the visits, participants will have blood and urine tests, complete questionnaires, and have other tests including brain and body imaging studies. 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.
  • 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....
Read the detailed description

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.

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.

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.

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). 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.

Outcome Measures

A 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).

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.

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.

Being tested
Linoleic Acid, Docosahexaenoic Acid, Eicosapentaenoic Acid
Keywords
Lipids, Obesity, Omega-3 Fatty Acids, Overweight
Medical subject headings
Weight Gain, Obesity, Overweight

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Linoleic AcidDietary supplement

  • Docosahexaenoic AcidDietary supplement

  • Eicosapentaenoic AcidDietary supplement

Study groups in NCT01251887
Study groupRoleWhat they receive
Diet A: Low omega-3 (n-3) + High linoleic acid (LA)ExperimentalStudy diet containing 8 % energy (en%) linoleic acid (LA), 0.4 % energy (en%) arachidonic acid (AA), 0.05 % omega-3 highly unsaturated fatty acids (HUFA) for 12 weeks
Receives: Dietary Supplement: Linoleic Acid; Dietary Supplement: Docosahexaenoic Acid; Dietary Supplement: Eicosapentaenoic Acid
Diet B: Low omega-3 (n-3) + Low linoleic acid (LA)ExperimentalStudy diet containing 1 % energy (en%) linoleic acid (LA), 0.4 % energy (en%) arachidonic acid (AA), 0.05 % omega-3 highly unsaturated fatty acids highly unsaturated fatty acids (HUFA) for 12 weeks
Receives: Dietary Supplement: Linoleic Acid; Dietary Supplement: Docosahexaenoic Acid; Dietary Supplement: Eicosapentaenoic Acid
Diet C: High omega-3 (n-3) + Low linoleic acid (LA)ExperimentalStudy diet containing 1 % energy (en%) linoleic acid (LA), 0.4 % energy (en%) arachidonic acid (AA), 0.81 % omega-3 (n-3) HUFA for 12 weeks
Receives: Dietary Supplement: Linoleic Acid; Dietary Supplement: Docosahexaenoic Acid; Dietary Supplement: Eicosapentaenoic Acid

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Proportion of n-6 HUFA in Total HUFA (%n-6 in HUFA)

    Tissue accretion of omega-6 (n-6) highly unsaturated fatty acids (HUFA) in fasting plasma as percent of total HUFA.

    Measured: Baseline

  2. Proportion of n-6 HUFA in Total HUFA (%n-6 in HUFA)

    Tissue accretion of omega-6 (n-6) highly unsaturated fatty acids (HUFA) in fasting plasma as percent of total HUFA.

    Measured: Week 4

  3. Proportion of n-6 HUFA in Total HUFA (%n-6 in HUFA)

    Tissue accretion of omega-6 (n-6) highly unsaturated fatty acids (HUFA) in fasting plasma as percent of total HUFA.

    Measured: Week 8

  4. Proportion of n-6 HUFA in Total HUFA (%n-6 in HUFA)

    Tissue accretion of omega-6 (n-6) highly unsaturated fatty acids (HUFA) in fasting plasma as percent of total HUFA.

    Measured: Week 12

Secondary outcomes (12)
  1. Proportion of n-6 HUFA Arachidonic Acid (AA)

    Tissue accretion of Arachidonic Acid (AA or 20:4n6), an omega-6 (n-6) highly unsaturated fatty acid, as measured in fasting plasma as a percent of total fatty acids.

    Measured: Baseline

  2. Proportion of n-6 HUFA Arachidonic Acid (AA)

    Tissue accretion of Arachidonic Acid (AA or 20:4n6), an omega-6 (n-6) highly unsaturated fatty acid, as measured in fasting plasma as a percent of total fatty acids.

    Measured: Week 4

  3. Proportion of n-6 HUFA Arachidonic Acid (AA)

    Tissue accretion of Arachidonic Acid (AA or 20:4n6), an omega-6 (n-6) highly unsaturated fatty acid, as measured in fasting plasma as a percent of total fatty acids.

    Measured: Week 8

  4. Proportion of n-6 HUFA Arachidonic Acid (AA)

    Tissue accretion of Arachidonic Acid (AA or 20:4n6), an omega-6 (n-6) highly unsaturated fatty acid, as measured in fasting plasma as a percent of total fatty acids.

    Measured: Week 12

  5. Proportion of n-3 HUFA Eicosapentaenoic Acid (EPA)

    Tissue accretion of eicosapentaenoic acid (EPA or 20:5n3), an omega-3 (n-3) highly unsaturated fatty acid (HUFA), as measured in fasting plasma as a percent of total fatty acids.

    Measured: Baseline

  6. Proportion of n-3 HUFA Eicosapentaenoic Acid (EPA)

    Tissue accretion of eicosapentaenoic acid (EPA or 20:5n3), an omega-3 (n-3) highly unsaturated fatty acid (HUFA), as measured in fasting plasma as a percent of total fatty acids.

    Measured: Week 4

  7. Proportion of n-3 HUFA Eicosapentaenoic Acid (EPA)

    Tissue accretion of eicosapentaenoic acid (EPA or 20:5n3), an omega-3 (n-3) highly unsaturated fatty acid (HUFA), as measured in fasting plasma as a percent of total fatty acids.

    Measured: Week 8

  8. Proportion of n-3 HUFA Eicosapentaenoic Acid (EPA)

    Tissue accretion of eicosapentaenoic acid (EPA or 20:5n3), an omega-3 (n-3) highly unsaturated fatty acid (HUFA), as measured in fasting plasma as a percent of total fatty acids.

    Measured: Week 12

  9. Proportion of n-3 HUFA Docosahexaenoic Acid (DHA)

    Tissue accretion of Docosahexaenoic Acid (DHA or 22:6n3), an omega-3 (n-3) highly unsaturated fatty acid (HUFA), as measured in fasting plasma as a percent of total fatty acids.

    Measured: Baseline

  10. Proportion of n-3 HUFA Docosahexaenoic Acid (DHA)

    Tissue accretion of Docosahexaenoic Acid (DHA or 22:6n3), an omega-3 (n-3) highly unsaturated fatty acid (HUFA), as measured in fasting plasma as a percent of total fatty acids.

    Measured: Week 4

  11. Proportion of n-3 HUFA Docosahexaenoic Acid (DHA)

    Tissue accretion of Docosahexaenoic Acid (DHA or 22:6n3), an omega-3 (n-3) highly unsaturated fatty acid (HUFA), as measured in fasting plasma as a percent of total fatty acids.

    Measured: Week 8

  12. Proportion of n-3 HUFA Docosahexaenoic Acid (DHA)

    Tissue accretion of Docosahexaenoic Acid (DHA or 22:6n3), an omega-3 (n-3) highly unsaturated fatty acid (HUFA), as measured in fasting plasma as a percent of total fatty acids.

    Measured: Week 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Dec 2010 (estimated)
  2. Study start12 Nov 2010
  3. Primary completion25 Jul 2018
  4. Study completion25 Jul 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Enrolment
85 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01251887
Sponsor's protocol ID
110028
Other IDs
11-AA-0028
Status last verified
25 Jul 2018
First submitted
1 Dec 2010
Last updated
5 Sep 2021
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Cota D. The role of the endocannabinoid system in the regulation of hypothalamic-pituitary-adrenal axis activity. J Neuroendocrinol. 2008 May;20 Suppl 1:35-8. doi: 10.1111/j.1365-2826.2008.01673.x.

    PubMed 18426497
  • Pagotto U, Marsicano G, Cota D, Lutz B, Pasquali R. The emerging role of the endocannabinoid system in endocrine regulation and energy balance. Endocr Rev. 2006 Feb;27(1):73-100. doi: 10.1210/er.2005-0009. Epub 2005 Nov 23.

    PubMed 16306385
  • Szmitko PE, Verma S. The endocannabinoid system and cardiometabolic risk. Atherosclerosis. 2008 Aug;199(2):248-56. doi: 10.1016/j.atherosclerosis.2008.03.011. Epub 2008 Mar 20.

    PubMed 18440538

Questions about this trial

What is this clinical trial studying?

A study testing Linoleic Acid, Docosahexaenoic Acid and Eicosapentaenoic Acid in people with Weight Gain and Healthy Subjects, run by National Institute on Alcohol Abuse and Alcoholism (NIAAA) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Sep 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of n-6 HUFA in Total HUFA (%n-6 in HUFA) (time frame: Baseline). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01251887, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Sep 2021.

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