Efficacy of Fish Oil or Olive Oil Supplementation on the Health Effects of Ozone Exposure in Healthy Young Subjects
Condition: Healthy; Dietary Supplement
Study type: Interventional
Phase: Phase 1

Summary: 
      Purpose: A growing body of epidemiological data suggests an increased risk of cardiovascular
      events associated with air pollution. One of the common air pollutants, ozone, has been shown
      to induce oxidative stress and inflammation in the cardiovascular and respiratory systems.
      This proposed study is to examine the efficacy of fish oil and olive oil in modulating
      cardiovascular and pulmonary functions after ozone exposure. The objective is to understand
      the mechanistic basis for the health effects of ozone relative to those air pollutants.
      Treatment groups will include forty healthy young adults who will be given dietary
      supplementation of fish oil or olive oil. A control group will consist of 20 healthy
      volunteers who will receive no supplements. After 4 weeks, subjects will be exposed to clean
      air for 2 hours on the first day, then ozone for 2 hours on the second day. Cardiac rhythm,
      pulmonary function, vascular responses, endothelial function, and markers of coagulation and
      airway inflammation pre- and post- ozone exposure will be measured. This study is designed to
      build on the previous nutritional supplement interventional studies (UNC IRB # 07-0190 and
      UNC IRB # 11-1807), in order to understand the mechanism of action of particulate pollutants
      in comparison to that of ozone, a known oxidant air contaminant.

      Participants: A total of sixty healthy 18-35 year-old male and female subjects will be
      involved in the study.

      Procedures (methods): Forty healthy young adults will receive dietary supplementation
      consisting of fish oil or olive oil for 4 weeks. The control group includes 20 healthy
      volunteers who will receive no supplements in the study. After 4 weeks of supplementation or
      control regiment, each subject will be exposed to clean air for 2 hours on the first day,
      then ozone for 2 hours on the second day.
    

Detailed description: 
      Ozone pollution is a common problem across the world, including in the US. This proposed
      study is to examine the efficacy of fish oil and olive oil in modulating cardiovascular and
      pulmonary functions after ozone exposure. Results from this study will also increase our
      understanding of how ozone exposure adversely affects the functioning of the human
      cardiovascular and respiratory systems. This understanding may be especially important for
      patients with cardiopulmonary diseases.

      Approximately 60 people will participate in this study.

      You should expect to be in this study for about a month, but your participation could
      possibly last for 6 months. There are 4 sessions, including a consenting session (today)
      which will last for about 4 hours. The two exposure-day sessions will last approximately 8-9
      hours each. There will also be an approximately 3-hour follow-up visit the day after your
      last exposure.

      What will happen if you take part in the study? Before you agree to participate in this
      study, you must read the consent forms in their entirety. The research and medical staff will
      then answer all your questions and explain all the risks involved in this study to your
      satisfaction.

      You should have already undergone a general physical examination to ensure that you are a
      suitable candidate for this study. If you are a female, you will be asked about your
      menstrual history. For all other female participants, a pregnancy test will be performed
      today, and this will be repeated on the exposure day if more than 7 days since last pregnancy
      test.

      Consenting Day We will go over the study in detail so that you will know what we will expect
      from you as a participant and what you should expect from us as investigators. If you agree
      to participate in the study, you will sign all study consent forms and receive one set of
      signed copies.

      You will have a breathing test (spirometry). You will breathe through a filter into a plastic
      device. Your lung function test results should meet certain criteria (Both Forced Vital
      Capacity (FVC) and Forced Expiatory Volume at the 1st second (FEV1) are equal to and greater
      than 80% of the reference value) to allow you to participate in the study.

      You will undergo a procedure for for induced sputum. If you are a non-producer or the quality
      of the induced sputum sample that you produce does not meet the study criteria (we will know
      the sputum quality in the next two days), we will exclude you from the study. If that
      happens, you will be reimbursed for the time and procedures for the consenting session. If
      you qualify, you will be given instructions to prepare for the exposure sessions. Then you
      will be scheduled for the exposure sessions.

      You will be give dietary supplementation of fish oil, olive oil or placebo for 4 weeks.
      Dietary and medication instructions will be given to restrict certain types of food and
      medicines during the supplementation period.

      Exposure days We will call you a few days before the exposure session to remind you of your
      scheduled visit. You should avoid smoke, fumes, alcohol, and strenuous exercise 24 hours
      prior to all visits, and abstain from pan fried or grilled meat after midnight of the
      exposure day.

      You will be asked to eat a light breakfast and arrive at the EPA medical station by 7:30 am.
      Please understand that it is very important that you arrive by this time in order for the
      study team to process all of the samples and data. Please note that we may have to cancel
      your participation if you arrive late.

      Prior to exposure, you will:

        -  Have your vital signs checked (heart rate, respiratory rate, blood pressure, oxygen
           saturation level, and fill out a symptom questionnaire electronically).

        -  Have your heart rhythm recorded by a Holter monitor. You will have (10)
           electrocardiogram (ECG) leads attached to your chest. It may be necessary to clean and
           shave the areas of your chest where these leads will be placed. Excessive deodorant,
           skin lotions, and body sprays may interfere with the function of some of these leads.
           Therefore, we ask you to not apply these to your chest area on the day you report to the
           HSF. The leads will be connected to 2 monitors (small recording devices about the size
           and weight of a cell phone) to obtain readings of your heart rate and rhythm. It is
           preferable that the electrodes will stay in place for approximately 2 ½ days as you will
           have this measured several times during the study, however, you will be given the option
           to remove the electrodes by the end of each exposure day. You will be asked to recline
           quietly for 30 minutes while collecting your heart rhythm. It is important that you do
           not fall asleep during this 30-minute period. These measurements will allow us to
           determine whether wood smoke exposure causes small changes in the ability of your
           nervous system to regulate how your heart beats.

        -  Have the diameter of an artery in your upper arm measured by an ultrasound machine
           (BAU). The ultrasound operator will scan your arm with a probe and then place a
           tourniquet on your arm, much like a cuff used to measure blood pressure. Measurement of
           the size of the artery will be made two times. First, you will be asked to rest quietly
           for 15 minutes, and then the first 90 second scan will be performed. Then the blood
           pressure cuff on your arm will be inflated for 5 minutes in order to temporarily stop
           the flow of blood. You may feel sensations similar to that when your foot "goes to
           sleep", such as "pins and needles" and tingling. After the pressure cuff is released, a
           second scan will be taken of the artery.

        -  Have your retinas imaged using an ophthalmic camera before and after each exposure, and
           on the follow-up visit. You will be asked to place your chin on a rest in front of the
           camera. We will take pictures of the inside of both of your eyes. Glasses or contacts
           have to be removed for this test. Please bring your own contact lens container and
           solutions.

        -  Approximately 60 ml blood drawn (about 4 tablespoons) before and after each exposure,
           and on the follow-up visit. We will test this blood to see if wood smoke affects the
           ability of your blood cells to function. A small portion of the blood sample will be
           used to measure the relative content of various fatty acids present in your blood. With
           your permission, we also store some of the blood that we obtain during the study for
           yet-to-be-determined tests in the future.

        -  Have a breathing test (spirometry).

        -  Enter the exposure chamber and be exposed to filtered air or ozone.

      During the exposure, you will:

      • Undergo exposure for 2 hours to either clean filtered air or ozone in the chamber. You will
      receive clean filtered air on one day and ozone on the other day. You will not be given the
      information of the sequence of the exposure. Chamber conditions will be at a comfortable
      temperature and relative humidity. You will do mild exercise on a stationary bicycle in the
      chamber every other 15 minutes alternating with resting period for a total of 1 hour of
      exercise per chamber exposure. The target ventilation rate will be maintained at 20 L/min/ m2
      and monitored by using pneumotach method. A study coordinator or other trained person will be
      seated outside the chamber observing you at all times. During the exposure, your heart will
      be monitored and the amount of oxygen present in your blood will be monitored by placing a
      device (pulse oximeter) on your finger. If it appears you are experiencing significant
      discomfort, breathing or heart problems, the exposure will be terminated immediately. In
      addition, you may elect to terminate the exposure at any time for any reason. If you do so,
      you will be paid in full for that day's session but will be ineligible for further
      participation in the study and any payments you would have received for future participation.

      Immediately following the exposure, you will repeat the pre-exposure procedures and have a
      low fat lunch brought by you.

        -  Once you complete the above procedures, you will have about 1-2 hour waiting time before
           the next procedure. You can bring your personal laptop or books to use during that time.
           You will not be able to eat any food during this break time.

        -  Have samples of your airway secretions collected using the induced sputum procedure. You
           will be asked to breathe in different saline solutions (up to 5%) to help you
           expectorate. We will coach you on the procedure. First, you will gargle and clear your
           throat, and the cough up samples from deep in your chest and spit them into a cup. Your
           lung function will be monitored during the procedure. Food must be avoided for 2 hours
           prior to this test.

        -  Be assessed and discharged by the study personnel.

      Follow up visit (about 3 hours) You will return to the HSF the next morning (approximately 18
      hours after your 2nd exposure) and you will repeat the pre-exposure procedures.
    

Intervention name(s): Ozone; Fish Oil; Olive Oil
Intervention type(s): Drug; Dietary Supplement; Dietary Supplement
Intervention description(s): After the four-week supplementation period, each subject will be blindly exposed on consecutive days to filtered air for 2 hours and to 0.3 ppm ozone for 2 hours, while undergoing intermittent moderate exercise (minute ventilation of 20 L/min/m²).; 3 (1-gram) soft-gels daily Commercially available, enteric-coated, soft-gels formulated to deliver >60% eicosapentaenoic/docosahexaenoic acids (EPA/DHA); 3 soft-gels daily Commercially available soft-gels containing 1 gram of USDA organic certified, cold pressed, extra virgin, olive oil
Other intervention name(s): Filtered air; omega-3 fatty acids (eicosapentaenoic/docosahexaenoic); extra virgin olive oil
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science
Keywords: Ozone exposure; Healthy Adults