A Pilot Study of Docosahexaenoic Acid (DHA) in Obese Menopausal Women

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Rockefeller University
ClinicalTrials.gov Identifier:
NCT01127867
First received: May 19, 2010
Last updated: May 16, 2013
Last verified: May 2013
  Purpose

This study aims to determine if a supplement of an omega-3-fatty acid (docosahexaenoic - DHA) lowers inflammation in human fat tissue thereby lowering estrogen production and the potential risk for breast, rectal and colon cancers. The investigators also aim to study how this occurs to discover the basis for other potential treatments to lower estrogen production in fat tissue and decrease the risk of breast cancer. Additionally, this study will evaluate the effectiveness of DHA supplements in reducing inflammation and the risk for colon cancer.


Condition Intervention
Breast Cancer
Rectal Cancer
Colon Cancer
Obesity
Dietary Supplement: dietary intervention

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Docosahexaenoic Acid (DHA) Reduces Inflammation and Aromatase Expression in Subcutaneous Fat and Inflammation in the Rectosigmoid Mucosa in Obese Postmenopausal Women: A Pilot Study

Resource links provided by NLM:


Further study details as provided by Rockefeller University:

Primary Outcome Measures:
  • Reduced subcutaneous fat [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    Reduced subcutaneous fat and colorectal mucosal inflammation changes between pre and post treatment as seen by histologic quantification of monocyte aggregations (crowns), CD68 and CD163 stained macrophages in fat biopsies, as well as, mediators of mucosal inflammatory and immune protein concentrations in rectosigmoid biopsies.


Secondary Outcome Measures:
  • multiplex bead assay/immunoassay [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]

    Lowered aromatase expression in fat biopsies accompanied by decreases in the synthetic enzyme COX1-MPGES-1 and/or increase in the catabolic enzyme 15-PGDH and associated changes in BRAC-1 and SIRT-1 expression.

    by immunohistochemical evaluation of CD68, CD168 and CD3 stained monocytes and through examination of the mRNA of imune inflammatory markers.

    Alteration in serum estradiol and testosterone levels and/or changes in circulating cytokines/chemokines measured by multiplex bead assay and immuoassay.



Estimated Enrollment: 17
Study Start Date: May 2010
Study Completion Date: April 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    Dietary Supplement: dietary intervention
    dietary intervention
Detailed Description:

Breast cancer and colorectal cancer are two of the most frequently seen cancers in the United States. Breast cancer occurs at all ages but is particularly common in post menopausal women. Obesity increases the risk of breast cancer primarily of the type that is stimulated by the female sex hormone estrogen. In obesity, fat cells produce estrogen which can alter breast tissue, while lowering blood estrogen reduces the incidence of breast cancer. Inflammation of fat tissue, the coronary blood vessels and the liver are also seen with obesity. Animal experiments have shown the inflammation in fat tissue increases the production of estrogen, thus reducing inflammation in fat tissue might lower estrogen levels and the risk of breast cancer in obese women. Obesity simultaneously increases the inflammation of colon tissue. Since chronic inflammation in the colon is a co-factor in rectal and colon cancers, reducing inflammation should lower the risk of developing these cancers as well. A diet high in omega-3-fatty acids, such as those found in fish oil, has been shown in mice to reduce inflammation and aromatase expression (rate limiting enzyme for estrogen synthesis) in fat tissue and to reduce inflammation in the colon of mice and humans.

This pilot study of five obese, postmenopausal women will include nutritional and medical evaluations, a four day inpatient hospital stay on a regular diet, and to measure the inflammation and the estrogen producing machinery and resting energy of each volunteer subject, as well as, biopsies of abdominal fat tissue and the inflammation in the sigmoid colon obtained by sigmoidoscopy. Following these baseline measurements, subjects will be provided DHA supplements to take daily for three months and requested to weigh themselves twice weekly at home with the goal of maintaining their weight. Telephone interviews will be performed at scheduled points to check-in with the subjects and after six weeks blood tests will be performed. At three months each subject will be readmitted to the hospital and repeat the tests performed before starting on the DHA supplement. If the study shows feasibility and positive results it will be extended to more subjects and other interventions in the future.

  Eligibility

Ages Eligible for Study:   40 Years to 70 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Post-menopausal defined as:

  1. 24 consecutive months without a menstrual period AND
  2. low serum estradiol level (<40 ng/ml) to be assessed at screening AND
  3. not taking any medication known to induce ammenorhea AND
  4. no known endocrine abnormality associated with irregular/absent menses.
  5. BMI greater than 35.

Exclusion Criteria:

  1. Currently taking any hormone therapy: oral, transplanted, vaginal, injected
  2. Currently taking NSAIDS (if > once a week, stopped < 30 days ago)
  3. Currently taking oral hypoglycemics
  4. Currently taking anticoagulants or stopped < 30 days ago
  5. Any history of a malignancy excluding basal and squamous cell skin cancer
  6. Blood Pressure > 150/90 at screening
  7. History of any bleeding disorder
  8. LFT results > 2x normal upper limits
  9. Renal lab value results > 2x normal upper limits
  10. Any condition or situation which, in the investigator's opinion, puts the patient at significant risk, could complicate the study results, or may interfere significantly with participation in the study.
  11. History of intestinal malabsorption
  12. RBC's (red blood cells) on screening urinalysis
  13. History of chronic diarrhea
  14. Using any drug study medications or multiple medications that might change the bowel lining.
  15. On any medications that can alter fat stores or large bowel inflammation as deemed by the principal investigator
  16. History of inflammatory bowel disease
  17. Abnormal thyroid function based on screening labs
  18. Currently using any weight control medication
  19. HIV positive as per POCT rapid test at screening
  20. Currently taking fish oil, omega-3 supplements or other herbals that exceed the GRAS (Generally Recognized As Safe)
  21. Fasting blood sugar greater than 126 mg/dL at screening
  22. Currently taking more than 3 antihypertensive medications
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01127867

Locations
United States, New York
The Rockefeller University
New York, New York, United States, 10065
Sponsors and Collaborators
Rockefeller University
Investigators
Principal Investigator: Peter Holt, MD The Rockefeller University
  More Information

Additional Information:
No publications provided

Responsible Party: Rockefeller University
ClinicalTrials.gov Identifier: NCT01127867     History of Changes
Other Study ID Numbers: PHO-0702
Study First Received: May 19, 2010
Last Updated: May 16, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Breast Neoplasms
Colonic Neoplasms
Rectal Neoplasms
Obesity
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms

ClinicalTrials.gov processed this record on April 15, 2014