Borage and Echium Seed Oils for Asthma
Condition: Asthma
MeSH terms: Asthma
Study type: Interventional
Phase: Phase 3

Summary: 
      This study plans to look at whether borage and echium seed oils (natural oils from two
      plants) help decrease asthma symptoms and affect cells involved in inflammation. The
      investigators also want to look at how these plant oils decrease the generation of
      inflammatory cells in people with asthma.
    

Detailed description: 
      To evaluate the mechanisms by which borage seed oil and echium seed oil block mediator
      generation in asthma, we performed a cross-over trial design to reduce the numbers of
      patients needed for the study. Each treatment period was six weeks with a six-week washout
      period. For simplicity all power calculations are made assuming a single factor or predictor
      variable and a single result or outcome variable. We focused on changes in mediator
      generation by effector cells. Calculations below suggest that we have resolution to pick up
      clinically meaningful effects of potentially important explanatory variables with acceptable
      or high power.

      1. Study Design The goals were to examine the mechanisms that underlie the effects of borage
      seed oil and echium seed oil on proinflammatory mediator production by effector leukocytes.

      In the treatment arm, subjects consumed 4.0 g/day borage seed oil and 7.0 g/day echium seed
      oil (containing totals of ~1.6 g/day of GLA and ~0.9 g/day of SDA). The oils were packaged in
      capsules each of which contained 1 gram of oil. Therefore subjects will ingest 10 capsules a
      day (3 in the morning, 3 in the afternoon, and 4 in the evening) with meals. In the placebo
      arm, subjects took matching capsules containing corn oil; three 1 gram capsules in the
      morning and afternoon, and four in the evening, with meals.

      The study began with a screening visit. All subjects had physician-diagnosed asthma. All
      performed a baseline set of lung function measurements. They entered a 2-week run-in period
      during which they kept a diary of peak flows, asthma symptoms, and beta agonist use. Subjects
      were instructed in peak flow technique and asked to perform three maneuvers each time. The
      maneuver was considered technically sufficient if the variation in the values obtained on the
      three attempts are with 10% of each other, and the highest value was recorded in a diary.
      Subjects whose diaries were > 80% complete entered the study and were randomly assigned to
      active treatment or placebo. Spirometry was repeated. Blood was taken for fatty acid
      composition of plasma and leukocytes, LT generation, and DNA for genotyping at the LTC4S
      locus. Subjects were provided with peak flow diaries, instructed in the appropriate
      performance or peak flow maneuvers, and asked to record morning and evening peak flow each
      day (reflecting the best of three efforts each time). After three weeks of treatment, diary
      cards will be collected and spirometry repeated. After six weeks of treatment, blood was
      drawn for safety monitoring, for measurements of fatty acids in plasma and leukocytes, and
      for the functional analyses. Spirometry was repeated. Subjects then entered a six-week
      washout period. Two weeks before the end of this period they again started to keep diary
      cards. At the conclusion of the 6-week washout period they entered the cross-over treatment
      phase (six weeks) which followed the same protocol as the first treatment period with
      assessment of fatty acid analyses, cellular function studies, safety monitoring, and
      spirometry. Pregnancy testing was performed before and after each treatment period. Dairy
      cards (with peak flow monitoring results) will be collected at each visit (3 week intervals
      during the placebo and active treatment arms of the study).

      3. Statistical Analyses

      a. Power Calculations - For simplicity all power calculations are made assuming a single
      factor or predictor variable and a single result or outcome variable. While a number of
      correlated outcomes will be investigated, we will focus on changes in mediator generation and
      levels of enzyme expression. Calculations below suggest that we have resolution to pick up
      clinically meaningful effects of potentially important explanatory variables with acceptable
      or high power.

      i. Biochemical Endpoints - Power is based on paired t-tests comparing continuous measures of
      response between treatment and placebo. We assume 40 subjects will be available after
      allowing for a drop out rate of 20% from our original sample of 50 subjects. For the endpoint
      of leukotriene production by leukocytes, the power calculations suggested that we will have
      80% power to detect a true within-subject difference of 0.8 of the within-subject SD between
      treatment and placebo with an α value of 0/05. On the basis of our previous studies, we
      assume a within-subject coefficient of variation (CV) of 13% for LTC4 generation. This will
      translate to an approximate detectable difference from 10.5% in these parameters.Using a
      paired two-sided t-test and prior mean(standard deviation) estimates for the placebo of
      .001464 ( .002268) and for the borage oil of .000289( .000709) , we would need 40subjects for
      80-90% power at a 0.05 level of significance to detect a change in LTC4S transcript, protein,
      and enzymatic activity of 50% between placebo and borage arms.

      b. Analysis Plan - Initially, we will present descriptive statistics (mean, standard
      deviation, range) for all endpoints to treatment and placebo groups. We will also present
      graphical plots of all measures across the study and for each group within each period. For
      the 2x2 crossover study, we will compare the treatment and control on each endpoint
      separately by employing a generalized mixed model approach with the predictors:
      group(sequence), patient nested within group as a random effect, period(dichotomous),
      treatment(dichotomous), and seasonality(dichotomous), with unstructured covariance. We will
      utilize mixed model diagnostics such as residual plots to assess goodness of fit.
    

Intervention name(s): Borage and Echium Seed Oils; Corn oil pills
Intervention type(s): Drug; Dietary Supplement
Intervention description(s): 4.0 g/day borage seed oil and 7.0 g/day echium seed oil. Pills will be taken three times per day for six weeks.; Corn oils pills will be taken three times per day for six weeks.
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Asthma; Borage; Echium; Botanical