The Chronic Obstructive Pulmonary Disease Fish Oil Pilot Trial

Chronic obstructive pulmonary disease is abbreviated as COPD and includes both emphysema and
chronic bronchitis. COPD is currently the fourth leading cause of death in the United
States. Unlike most major medical diseases, the morbidity and mortality from COPD continue
to rise in the US. In 2000, over 10 million Americans carried a physician diagnosis of COPD
and 120,000 Americans died from this disease. Additionally, from the year 1980 to the year
2000, the number of cases of COPD among women nearly doubled and the prevalence among
African Americans increased by 61%. Unlike the other leading causes of death, no medical
therapies currently available improve the course of disease or affect survival in COPD.
Current therapies for COPD that improve survival in COPD are limited to smoking cessation,
oxygen therapy, and possibly surgery. Medical therapies such as inhalers and pills improve
symptoms and reduce COPD exacerbations ("attacks"), but have not been shown to slow down the
progression of the disease.

Recent investigations suggest that endothelial dysfunction and chronic inflammation is
fundamental to COPD. Fish oil intake improves endothelial dysfunction and lowers levels of
inflammatory intermediaries. These inflammatory intermediaries can be measured in the blood
and are potentially important in the development of COPD. Large observational studies
demonstrate that participants who eat high amounts of fish oil develop less COPD and have
lower levels of these inflammatory intermediaries.

The Chronic Obstructive Pulmonary Disease Fish Oil (COD-Fish) Pilot Trial will enroll 40-45
participants with COPD. These participants will be randomized to receive Omax3[TM] or
placebo (containing corn oil). Omax3[TM] (Cenestra Health) is a 1 gram softgel capsule
containing 94.5% omega-3 fatty acids. Each participant will be taking 3 capsules of either
Omax3[TM] or matching placebo. The investigators and the subjects will be blinded, meaning
that neither the investigators nor the subjects will know if they are taking Omax3[TM] or
placebo. All participants will perform a number of noninvasive tests at study entry as well
as every two months for a total of six months. They will also undergo pulmonary function
testing, flow-mediated dilation (FMD), peripheral arterial tonometry (PAT), six minute-walk
tests (6MWT), blood drawing and answer questionnaire data. Thirty participants who agree to
it will undergo a separate procedure to collect cells from inside a forearm vein for
analysis to be compared to 30 controls. The main purpose of this trial is to examine the
effect of Omax3[TM] on endothelial function as measured by change in FMD in patients with
COPD. We hypothesize that in subjects with COPD, treatment with Omax3[TM] will increase
FMD.

Inclusion Criteria:

- Post-bronchodilator FEV1/FVC ratio <70%

- Post-bronchodilator FEV1 <65% predicted.

- Clinical diagnosis of COPD

- Stable medical regimen for 30 days prior to enrollment

- Age > 40 years old

- History of former cigarette smoking, > or = 10 pack years

Exclusion Criteria:

- COPD exacerbation or hospitalization for COPD in the past 30 days

- Confirmed history of physician-diagnosed asthma

- History of unrelated pulmonary disease (e.g. interstitial lung disease,
thromboembolic disease)

- Status-post lung transplantation or Lung volume reduction surgery (LVRS)

- Systolic blood pressure >170mmHg or<100mmHg at rest, diastolic blood pressure >100 at
rest, or resting HR >120.

- Active cigarette smoking

- Clinical diagnosis of left-sided congestive heart failure

- Clinical diagnosis of coronary artery disease

- Clinical diagnosis of cerebrovascular disease

- Clinical diagnosis of peripheral vascular disease

- Prior history of stroke or myocardial infarction

- Clinical diagnosis of obstructive sleep apnea

- Pregnancy (known, and screen with urine BHCG) or current breastfeeding

- Contraindication to Omax3[TM] use, including a history of hypersensitivity to
Omax3[TM]

- Current use of high-dose fish oil capsules (defined as >1 or 2 grams/day of omega-3
fatty acids)

- Current use of Coumadin

- Elevated ALT greater than 2 times the upper limit of normal at baseline

- Congenital abnormality of the arm or hand

- Raynaud's Phenomenon

- History of radical mastectomy or removal or axillary lymph nodes

- Allergy to fish or corn oil

- Unstable angina during previous month

- End Stage Liver Disease, Cirrhosis

- Body Mass Index > 35

For Non-COPD controls (Same Inclusion and exclusion criteria, except for inclusion, must
NOT have the following:)

- Post-bronchodilator FEV1/FVC ratio >70%

- Post-bronchodilator FEV1 <65% predicted.

- Clinical diagnosis of COPD