Bronchial Asthma
Conditions
Keywords
Asthma, Fatty acids, Leukotrienes, Diet
Brief summary
The aim of this trial is to determine the efficacy of a combination of two botanicals oils, borage seed oil and echium seed oil, as a potential treatment for bronchial asthma.
Detailed description
Leukotrienes are important in the pathogenesis of inflammation, and leukotriene modifying drugs are now an established treatment for bronchial asthma and rhinitis. Drugs that inhibit the biosynthesis of leukotrienes are likely to be more effective than the currently available drugs that antagonize a single leukotriene receptor. Dietary supplementation with gamma linolenic acid (GLA) in borage seed oil provides effective inhibition of leukotriene generation but also increases circulating free arachidonic acid (AA), which has pro-inflammatory potential. The n-3 fatty acid, eicosapentaenoic acid (EPA), prevented the conversion of GLA to AA. However, EPA is extracted from fish oil, is not well-tolerated due to its taste, and at higher doses appeared to blunt the inhibition of leukotriene biosynthesis by GLA. Stearidonic acid (SDA) is a precursor of EPA that is extracted from Echium plantagineum; it is converted to EPA in humans and it does not have the organoleptic properties of EPA. We recently completed a dose-ranging study in which we determined the dose of SDA that is sufficient to inhibit the rise in circulating levels of arachidonic acid while maintaining effective inhibition of leukotriene generation. The goal of the present study is to test the efficacy of dietary supplementation with GLA and SDA (provided in borage seed oil and echium seed oil) in treating bronchial asthma.
Interventions
DRUGBorage Seed Oil and Echium Seed Oil
2 g/day of borage seed oil and 7 g/day of echium seed oil to provide 1.6 g/day of GLA and 0.9 g/day of SDA.
DIETARY_SUPPLEMENTCorn Oil
9 g/day of corn oil
Sponsors
Wake Forest University Health Sciences
National Center for Complementary and Integrative Health (NCCIH)
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of bronchial asthma * Male or female 18 years to 65 years of age * FEV1 50 to 90% of predicted, or personal best. * Improvement of \>=12% FEV1 with bronchodilator
Exclusion criteria
* Pregnant or nursing * Smoking history of \> 10 pack years or active smoking within the past year. * Due to possible effects on leukotriene biosynthesis, use of the following asthma treatments within the preceding month will be
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Forced Expiratory Volume in 1 Second (FEV1) | 6 weeks | Forced expiratory volume in 1 second (FEV1) in plant seed oil vs. placebo |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Peak Flow Rate (PEFR) | 6 weeks | Morning Peak Flow Rate in plant seed oil vs. placebo |
| Frequency of Rescue Use of Short Acting Beta-2 Agonists | 6 weeks | Average number of puffs of albuterol daily in plant seed oil vs. placebo |
| Positive FEV1 Percent Predicted Change Among C Allele Carriers and A Homozygotes | 6 weeks on each treatment assignment | Number of participants with positive change in FEV1 % predicted (\>0%) among C allele carriers and A homozygotes in each arm |
| Night-time Wakenings | 6 weeks | Average number of night-time wakenings in plant seed oil vs. placebo |
| Urinary Leukotriene Levels | 6 weeks | Urinary leukotriene levels in plant seed oil vs. placebo |
| Day-time Symptoms of Bronchial Asthma | 6 weeks | Day-time symptom scores in plant seed oil vs. placebo. 0 = Absent: No symptoms 1. = Mild: Symptom did not interfere with normal daily activity or sleep 2. = Moderate: Symptom was sufficient to interfere with normal daily activity or sleep 3. = Severe: Symptom was so severe as to prevent normal daily activity or sleep These numbers were used for 1. Shortness of breath 2. Chest tightness 3. Wheezing 4. Cough 5. Phlegm/Mucus. The total score is the sum of the 5 item scores, for a range of 0-15. A higher score represents more severe symptoms. Each participant's score is the average of varying numbers of diary cards. The treatment phase visits at 6 weeks consisted of 3 weeks of diary cards with a +/- 5 day window. The baseline visits had 2 weeks of diary cards with a +/- 5 day window. The treatment phase measures are adjusted for the baseline measures. |
Countries
United States
Participant flow
Pre-assignment details
43 subjects were enrolled and signed consent; however, only 39 were randomized into a treatment group. 3 subjects screen failed and 1 subject was lost to follow up prior to randomization.
Participants by arm
| Arm | Count |
|---|---|
| All Study Particpants Includes patients scheduled to receive Borage and Echium seed oil first and participants scheduled to receive placebo first. | 39 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 5 |
Baseline characteristics
| Characteristic | All Study Particpants |
|---|---|
| Age, Customized Age | 43 years |
| Age, Customized Age Category <=18 years | 0 Participants |
| Age, Customized Age Category >=65 years | 0 Participants |
| Age, Customized Age Category Between 18 and 65 years | 39 Participants |
| Region of Enrollment United States | 39 participants |
| Sex/Gender, Customized Gender Female | 27 Participants |
| Sex/Gender, Customized Gender Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 13 / 28 | 14 / 28 | 6 / 14 | 5 / 14 |
| serious Total, serious adverse events | 0 / 28 | 0 / 28 | 1 / 14 | 0 / 14 |
Outcome results
Primary
Forced Expiratory Volume in 1 Second (FEV1)
Forced expiratory volume in 1 second (FEV1) in plant seed oil vs. placebo
Time frame: 6 weeks
Population: Includes participants that completed the study.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Plant Seed Oil | Forced Expiratory Volume in 1 Second (FEV1) | 2.31 liters |
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) | 2.25 liters |
Secondary
Day-time Symptoms of Bronchial Asthma
Day-time symptom scores in plant seed oil vs. placebo. 0 = Absent: No symptoms 1. = Mild: Symptom did not interfere with normal daily activity or sleep 2. = Moderate: Symptom was sufficient to interfere with normal daily activity or sleep 3. = Severe: Symptom was so severe as to prevent normal daily activity or sleep These numbers were used for 1. Shortness of breath 2. Chest tightness 3. Wheezing 4. Cough 5. Phlegm/Mucus. The total score is the sum of the 5 item scores, for a range of 0-15. A higher score represents more severe symptoms. Each participant's score is the average of varying numbers of diary cards. The treatment phase visits at 6 weeks consisted of 3 weeks of diary cards with a +/- 5 day window. The baseline visits had 2 weeks of diary cards with a +/- 5 day window. The treatment phase measures are adjusted for the baseline measures.
Time frame: 6 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Plant Seed Oil | Day-time Symptoms of Bronchial Asthma | 2.51 units on a scale |
| Placebo | Day-time Symptoms of Bronchial Asthma | 1.61 units on a scale |
Secondary
Frequency of Rescue Use of Short Acting Beta-2 Agonists
Average number of puffs of albuterol daily in plant seed oil vs. placebo
Time frame: 6 weeks
Population: one participant is missing some data on this measure
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Plant Seed Oil | Frequency of Rescue Use of Short Acting Beta-2 Agonists | 0.69 Avg number of puffs of albuterol daily |
| Placebo | Frequency of Rescue Use of Short Acting Beta-2 Agonists | 0.50 Avg number of puffs of albuterol daily |
Secondary
Night-time Wakenings
Average number of night-time wakenings in plant seed oil vs. placebo
Time frame: 6 weeks
Population: one participant is missing some night-time wakening data
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Plant Seed Oil | Night-time Wakenings | 0.16 average number of night-time wakenings |
| Placebo | Night-time Wakenings | 0.13 average number of night-time wakenings |
Secondary
Peak Flow Rate (PEFR)
Morning Peak Flow Rate in plant seed oil vs. placebo
Time frame: 6 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Plant Seed Oil | Peak Flow Rate (PEFR) | 337.13 liters/minute |
| Placebo | Peak Flow Rate (PEFR) | 339.34 liters/minute |
Secondary
Positive FEV1 Percent Predicted Change Among C Allele Carriers and A Homozygotes
Number of participants with positive change in FEV1 % predicted (\>0%) among C allele carriers and A homozygotes in each arm
Time frame: 6 weeks on each treatment assignment
Population: Patients who are C allele carriers or A homozygotes
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Plant Seed Oil | Positive FEV1 Percent Predicted Change Among C Allele Carriers and A Homozygotes | C-allele Carriers | 6 Participants |
| Plant Seed Oil | Positive FEV1 Percent Predicted Change Among C Allele Carriers and A Homozygotes | A Homozygotes | 11 Participants |
| Placebo | Positive FEV1 Percent Predicted Change Among C Allele Carriers and A Homozygotes | C-allele Carriers | 2 Participants |
| Placebo | Positive FEV1 Percent Predicted Change Among C Allele Carriers and A Homozygotes | A Homozygotes | 10 Participants |
Secondary
Urinary Leukotriene Levels
Urinary leukotriene levels in plant seed oil vs. placebo
Time frame: 6 weeks
Population: one participant was missing some urinary leukotriene data
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Plant Seed Oil | Urinary Leukotriene Levels | 0.101 ng/ml |
| Placebo | Urinary Leukotriene Levels | 0.088 ng/ml |