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

Docosahexaenoic Acid (DHA) Reduces Inflammation and Aromatase Expression in Subcutaneous Fat in Obese Postmenopausal Women: A Pilot Study

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 cancer. 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.

Study Overview

• Status: Completed
• Conditions: Obesity; Breast Cancer
• Intervention / Treatment: Dietary supplement: dietary intervention

Detailed Description

Breast cancer is one 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. 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.

This pilot study of five obese, post-menopausal women and an additional 12 morbidly obese post-menopausal women will include nutritional and medical evaluations, a four day inpatient hospital stay on a regular diet, to measure the inflammation and the estrogen producing machinery of each volunteer subject. 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 a return visit to the OPRC will be conducted to assess progress and provide additional supplements. 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.

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • The Rockefeller University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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 ammenorrhea AND
4. no known endocrine abnormality associated with irregular/absent menses.
5. BMI 35-50.

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 anticoagulant mediation or stopped < 30 days ago
5. History of any malignancy or cancer treatment in the past 3 years
6. Blood Pressure > 150/90 at screening
7. History of any bleeding disorder
8. Screening LFT results > 2x normal upper limits
9. Screening renal lab 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. Screening urinalysis positive for blood
13. History of chronic diarrhea
14. History positive for HIV
15. Currently on any medication that can alter fat stores or large bowel inflammation as deemed by the principal investigator
16. History of inflammatory bowel disease
17. Screening thyroid function test abnormal
18. Currently taking 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) levels
21. Fasting blood sugar greater than 126 mg/dL at screening
22. Currently taking more than 3 antihypertensive medications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduced subcutaneous fat (obese)	Reduced subcutaneous fat inflammation changes between pre and post treatment for 5 pilot subject as seen by histologic quantification of monocyte aggregations (crowns), CD68 and CD163 stained macrophages in fat biopsies.	6 weeks
Reduced subcutaneous fat (morbidly obese)	Reduced subcutaneous fat between pre and post treatment for an additional 12 morbidly obese subjects as seen by histologic quantification of monocyte aggregations (crowns), CD68 and CD163 stained macrophages in fat biopsies.	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
multiplex bead assay/immunoassay	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 in fat biopsies. Alteration in serum estradiol and testosterone levels and/or changes in circulating cytokines/chemokines measured by multiplex bead assay and immunoassay.	6 weeks

Collaborators and Investigators

• Sponsor: Rockefeller University
• Investigators: Principal Investigator: Peter Holt, MD, The Rockefeller University

Publications and helpful links

Helpful Links

• The Rockefeller University clinical research information page

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: May 19, 2010
• First Submitted That Met QC Criteria: May 20, 2010
• First Posted (Estimate): May 21, 2010

Study Record Updates

• Last Update Posted (Actual): March 13, 2017
• Last Update Submitted That Met QC Criteria: March 9, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Other Study ID Numbers: PHO-0702

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No