Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| P50AT002782 | U.S. NIH Grant/Contract | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Wake Forest University Health Sciences | OTHER |
| National Center for Complementary and Integrative Health (NCCIH) | NIH |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1: Borage Seed Oil and Echium Seed Oil | Experimental | Borage/Echium plant seed oils: 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. |
|
| 2: Placebo Comparator | Placebo Comparator | Placebo comparator: 9 g/day corn oil |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Borage Seed Oil and Echium Seed Oil | Drug | 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. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Forced Expiratory Volume in 1 Second (FEV1) | Forced expiratory volume in 1 second (FEV1) in plant seed oil vs. placebo | 6 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 6 weeks on each treatment assignment |
| Peak Flow Rate (PEFR) |
Not provided
Inclusion Criteria:
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 exclusion criteria:
Treatment within the previous three months with omalizumab (monoclonal antibody directed against IgE)
Subjects will not be permitted to take non-steroidal anti-inflammatory drugs in the week prior to any measurements of ex vivo leukotriene generation because of their effects on leukotriene biosynthesis via inhibition of prostaglandin generation.
A history of aspirin-sensitive asthma
Significant abnormalities in CBC, differential white cell count, renal function, and liver function, or urinalysis.
Any serious co-morbid medical condition.
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Elliot Israel, MD | Brigham and Women's Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Asthma Research Center, Brigham and Women's Hospital | Boston | Massachusetts | 02115 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 12716664 | Background | James MJ, Ursin VM, Cleland LG. Metabolism of stearidonic acid in human subjects: comparison with the metabolism of other n-3 fatty acids. Am J Clin Nutr. 2003 May;77(5):1140-5. doi: 10.1093/ajcn/77.5.1140. | |
| 8609415 | Background | Chilton-Lopez, Surette ME, Swan DD, Fonteh AN, Johnson MM, Chilton FH. Metabolism of gammalinolenic acid in human neutrophils. J Immunol. 1996 Apr 15;156(8):2941-7. |
| Label | URL |
|---|---|
| Asthma Research Center, Brigham and Women's Hospital | View source |
Not provided
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.
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | 1 - Borage Seed Oil and Echium Seed Oil, Then Placebo | Borage/Echium plant seed oils: 6.0 g/day borage seed oil and 6.0 g/day echium seed oil) (containing totals of ~ 1.7 g/day of GLA and 0.7 g/day of SDA) 3x day for 3 weeks followed a 3-week washout period, then Placebo (11 g/day corn oil) 3x day for 3 weeks. |
| FG001 | 2 - Placebo, Then Borage Seed Oil and Echium Seed Oil | Placebo (11 g of corn oil/day) 3x day for 3 weeks followed by a 3-week washout period, then Borage/Echium plant seed oils: 6.0 g/day borage seed oil and 6.0 g/day echium seed oil) (containing totals of ~ 1.7 g/day of GLA and 0.7 g/day of SDA) 3x day for 3 weeks. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | All Study Particpants | Includes patients scheduled to receive Borage and Echium seed oil first and participants scheduled to receive placebo first. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Forced Expiratory Volume in 1 Second (FEV1) | Forced expiratory volume in 1 second (FEV1) in plant seed oil vs. placebo | Includes participants that completed the study. | Posted | Mean | 95% Confidence Interval | liters | 6 weeks |
|
Adverse events data were collected for one year.
Adverse events data were collected for one year, from the time of first patient enrollment to the last date of adverse event resolution.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Plant Seed Oil | Borage/Echium plant seed oils: 6.0 g/day borage seed oil and 6.0 g/day echium seed oil) (containing totals of ~ 1.7 g/day of GLA and 0.7 g/day of SDA) |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Wheeze | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | subject experienced phlegm, cough, and wheeze during washout phase |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Drop in Hemoglobin | Blood and lymphatic system disorders | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Elliot Israel, MD | Brigham and Women's Hospital | 617-732-2801 | eisrael@partners.org |
Not provided
| ID | Term |
|---|---|
| D001249 | Asthma |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C079363 | borage oil |
| D003314 | Corn Oil |
| ID | Term |
|---|---|
| D004042 | Dietary Fats, Unsaturated |
| D004041 | Dietary Fats |
| D005223 | Fats |
| D008055 | Lipids |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Corn Oil | Dietary Supplement | 9 g/day of corn oil |
|
Morning Peak Flow Rate in plant seed oil vs. placebo |
| 6 weeks |
| Frequency of Rescue Use of Short Acting Beta-2 Agonists | Average number of puffs of albuterol daily in plant seed oil vs. placebo | 6 weeks |
| Day-time Symptoms of Bronchial Asthma | Day-time symptom scores in plant seed oil vs. placebo. 0 = Absent: No symptoms
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. | 6 weeks |
| Night-time Wakenings | Average number of night-time wakenings in plant seed oil vs. placebo | 6 weeks |
| Urinary Leukotriene Levels | Urinary leukotriene levels in plant seed oil vs. placebo | 6 weeks |
| 9237935 | Background | Johnson MM, Swan DD, Surette ME, Stegner J, Chilton T, Fonteh AN, Chilton FH. Dietary supplementation with gamma-linolenic acid alters fatty acid content and eicosanoid production in healthy humans. J Nutr. 1997 Aug;127(8):1435-44. doi: 10.1093/jn/127.8.1435. |
| 10917903 | Background | Barham JB, Edens MB, Fonteh AN, Johnson MM, Easter L, Chilton FH. Addition of eicosapentaenoic acid to gamma-linolenic acid-supplemented diets prevents serum arachidonic acid accumulation in humans. J Nutr. 2000 Aug;130(8):1925-31. doi: 10.1093/jn/130.8.1925. |
| 12852710 | Background | Surette ME, Koumenis IL, Edens MB, Tramposch KM, Chilton FH. Inhibition of leukotriene synthesis, pharmacokinetics, and tolerability of a novel dietary fatty acid formulation in healthy adult subjects. Clin Ther. 2003 Mar;25(3):948-71. doi: 10.1016/s0149-2918(03)80116-9. |
| 12852711 | Background | Surette ME, Koumenis IL, Edens MB, Tramposch KM, Clayton B, Bowton D, Chilton FH. Inhibition of leukotriene biosynthesis by a novel dietary fatty acid formulation in patients with atopic asthma: a randomized, placebo-controlled, parallel-group, prospective trial. Clin Ther. 2003 Mar;25(3):972-9. doi: 10.1016/s0149-2918(03)80117-0. |
| 25485197 | Derived | Kazani S, Arm JP, Boyce J, Chhay H, Dutile S, Wechsler ME, Govindarajulu U, Ivester P, Ainsworth HC, Sergeant S, Chilton FH, Israel E. LTC4 synthase polymorphism modifies efficacy of botanical seed oil combination in asthma. Springerplus. 2014 Nov 6;3:661. doi: 10.1186/2193-1801-3-661. eCollection 2014. |
| years |
|
| Age, Customized | Count of Participants | Participants |
|
| Sex/Gender, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Units | Counts |
|---|
| Participants |
|
|
| 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 | Patients who are C allele carriers or A homozygotes | Posted | Count of Participants | Participants | 6 weeks on each treatment assignment |
|
|
|
| Secondary | Peak Flow Rate (PEFR) | Morning Peak Flow Rate in plant seed oil vs. placebo | Posted | Mean | 95% Confidence Interval | liters/minute | 6 weeks |
|
|
|
| Secondary | Frequency of Rescue Use of Short Acting Beta-2 Agonists | Average number of puffs of albuterol daily in plant seed oil vs. placebo | one participant is missing some data on this measure | Posted | Mean | 95% Confidence Interval | Avg number of puffs of albuterol daily | 6 weeks |
|
|
|
| Secondary | Day-time Symptoms of Bronchial Asthma | Day-time symptom scores in plant seed oil vs. placebo. 0 = Absent: No symptoms
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. | Posted | Mean | 95% Confidence Interval | units on a scale | 6 weeks |
|
|
|
| Secondary | Night-time Wakenings | Average number of night-time wakenings in plant seed oil vs. placebo | one participant is missing some night-time wakening data | Posted | Mean | 95% Confidence Interval | average number of night-time wakenings | 6 weeks |
|
|
|
| Secondary | Urinary Leukotriene Levels | Urinary leukotriene levels in plant seed oil vs. placebo | one participant was missing some urinary leukotriene data | Posted | Mean | 95% Confidence Interval | ng/ml | 6 weeks |
|
|
|
| 0 |
| 28 |
| 13 |
| 28 |
| EG001 | Placebo | Placebo (11 g of corn oil/day) | 0 | 28 | 14 | 28 |
| EG002 | Washout After Plant Seed Oil | Washout period between first (plant seed oil) and second (placebo) treatment assignments | 1 | 14 | 6 | 14 |
| EG003 | Washout After Placebo | Washout period between first (placebo) and second (plant seed oil) treatment assignments | 0 | 14 | 5 | 14 |
|
| drop in hematocrit | Blood and lymphatic system disorders | Systematic Assessment |
|
| stomach ache | Gastrointestinal disorders | Systematic Assessment |
|
| food poisoning | Gastrointestinal disorders | Systematic Assessment |
|
| urticaria | Immune system disorders | Systematic Assessment |
|
| fatigue | General disorders | Systematic Assessment |
|
| allergies | Immune system disorders | Systematic Assessment |
|
| candidiasis | Infections and infestations | Systematic Assessment |
|
| uterine fibroid | Reproductive system and breast disorders | Systematic Assessment |
|
| Upper Respiratory Infection | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| cough, chest tightness | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| worsening asthma symptoms | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| bronchitis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| sore throat | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| bruised rib | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
Not provided
Not provided
| D012130 |
| Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| D005224 |
| Fats, Unsaturated |
| D010938 | Plant Oils |
| D009821 | Oils |
| D028321 | Plant Preparations |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |
| D005502 | Food |
| D000066888 | Diet, Food, and Nutrition |
| D010829 | Physiological Phenomena |
| D019602 | Food and Beverages |
| A Homozygotes |
|
|