Trial Outcomes & Findings for Borage and Echium Seed Oils for Asthma (NCT NCT01560988)

NCT ID: NCT01560988

Last Updated: 2018-04-09

Results Overview

Primary outcome measures will be changes in the generation of LTC4 production by granulocytes. This was calculated by the difference between the amount produced at the start of each arm and at the end of each arm (i.e., two values were obtained in each arm and used to calculate the difference, and the differences were compared as a delta-delta).

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 62 participants
• Primary outcome timeframe: Assessed at 2, 8, 14, and 20 weeks
• Results posted on: 2018-04-09

Participant Flow

Participant milestones

Measure	First Borage and Echium, Then Corn Oil Borage and Echium Seed Oils: 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, followed by a 6 week washout. Then, subjects were crossed over to receive corn oil (10 g) daily for six weeks	First Corn Oil, Then Borage and Echium Seed Oil Corn oil pills will be taken for six weeks, followed by a 6 week washout. Then subjects received borage and echium oil tablets for six week.
First Intervention (Six Weeks) STARTED	32	30
First Intervention (Six Weeks) COMPLETED	22	26
First Intervention (Six Weeks) NOT COMPLETED	10	4
Washout (Six Weeks) STARTED	22	26
Washout (Six Weeks) COMPLETED	20	24
Washout (Six Weeks) NOT COMPLETED	2	2
Second Intervention (Six Weeks) STARTED	20	24
Second Intervention (Six Weeks) COMPLETED	18	22
Second Intervention (Six Weeks) NOT COMPLETED	2	2

Reasons for withdrawal

Measure	First Borage and Echium, Then Corn Oil Borage and Echium Seed Oils: 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, followed by a 6 week washout. Then, subjects were crossed over to receive corn oil (10 g) daily for six weeks	First Corn Oil, Then Borage and Echium Seed Oil Corn oil pills will be taken for six weeks, followed by a 6 week washout. Then subjects received borage and echium oil tablets for six week.
First Intervention (Six Weeks) Lost to Follow-up	7	4
First Intervention (Six Weeks) Withdrawal by Subject	3	0
Washout (Six Weeks) Lost to Follow-up	2	2

Baseline Characteristics

Borage and Echium Seed Oils for Asthma

Baseline characteristics by cohort

Measure	All Study Participants n=62 Participants Participants were randomized to receive either borage and echium oils first, and corn oil second, or vice versa
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	62 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	43 Participants n=5 Participants
Sex: Female, Male Male	19 Participants n=5 Participants
Region of Enrollment United States	62 participants n=5 Participants

PRIMARY outcome

Timeframe: Assessed at 2, 8, 14, and 20 weeks

Population: We analyzed all samples available, including from subjects who did not complete the entire protocol (i.e., 40 subjects crossed over and completed both arms, but 44 completed the corn oil and 44 completed the borage and echium arm, and the overlap was incomplete). Thus, the number of subjects differs from the total number of subjects per arm.

Primary outcome measures will be changes in the generation of LTC4 production by granulocytes. This was calculated by the difference between the amount produced at the start of each arm and at the end of each arm (i.e., two values were obtained in each arm and used to calculate the difference, and the differences were compared as a delta-delta).

Outcome measures

Measure	Borage and Echium Seed Oils n=39 Participants Borage and echium seed oils will be taken for six weeks. Borage and Echium Seed Oils: 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 Oil Pills n=38 Participants Corn oil pills will be taken for six weeks. Corn oil pills: Corn oils pills will be taken three times per day for six weeks.
Cellular Changes That Occur With Borage and Echium Seed Oil Supplementation	5.06 ng Standard Deviation 15.7	2.56 ng Standard Deviation 15.0

PRIMARY outcome

Timeframe: At 2, 8, 14, and 20 weeks

Population: We analyzed all samples available, including from subjects who did not complete the entire protocol (i.e., 40 subjects crossed over and completed both arms, but 44 completed the corn oil and 44 completed the borage and echium arm, and the overlap was incomplete). Thus, the number of subjects differs from the total number of subjects per arm

Primary outcome measures will be changes in the generation of LTB4 production by granulocytes. This was calculated by the difference between the amount produced at the start of each arm and at the end of each arm (i.e., two values were obtained in each arm and used to calculate the difference, and the differences were compared as a delta-delta). A negative number implies that the level of LTB4 produced by granulocytes at the end of the arm was less than the amount produced at the start of the arm, while a positive number means that more was generated at the end than at the beginning.

Outcome measures

Measure	Borage and Echium Seed Oils n=39 Participants Borage and echium seed oils will be taken for six weeks. Borage and Echium Seed Oils: 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 Oil Pills n=38 Participants Corn oil pills will be taken for six weeks. Corn oil pills: Corn oils pills will be taken three times per day for six weeks.
Change in LTB4 Production	-.99 ng Standard Deviation 8.73	0.12 ng Standard Deviation 6.21

SECONDARY outcome

Timeframe: Assessed at 2, 8, 14, and 20 weeks

Population: We analyzed all samples available, including from subjects who did not complete the entire protocol (i.e., 40 subjects crossed over and completed both arms, but 44 completed the corn oil and 44 completed the borage and echium arm, and the overlap was incomplete). Thus, the number of subjects differs from the total number of subjects per arm

Secondary outcome measures include changes in concentrations of omega 3 fatty acids in cell pellets, indicating incorporation of botanical oil metabolites in cell membrane lipids.. This was calculated by the difference between the amount present at the start of each arm and at the end of each arm (i.e., two values were obtained in each arm and used to calculate the difference, and the differences were compared as a delta-delta).

Outcome measures

Measure	Borage and Echium Seed Oils n=39 Participants Borage and echium seed oils will be taken for six weeks. Borage and Echium Seed Oils: 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 Oil Pills n=39 Participants Corn oil pills will be taken for six weeks. Corn oil pills: Corn oils pills will be taken three times per day for six weeks.
Measure of DHA in Cell Pellets	1.18 ng Standard Deviation 8.51	-1.01 ng Standard Deviation 11.00

SECONDARY outcome

Timeframe: Assessed at 2, 8, 14, and 20 weeks

Population: We analyzed all samples available, including from subjects who did not complete the entire protocol (i.e., 40 subjects crossed over and completed both arms, but 44 completed the corn oil and 44 completed the borage and echium arm, and the overlap was incomplete). Thus, the number of subjects differs from the total number of subjects per arm

Changes in lung function (forced expiratory volume in 1 second) will be assessed via spirometry at each visit. This was calculated by the difference between the FEV1 at weeks 2 and 8 versus weeks 14 and 20. The differences were compared as a delta-delta. A negative number for this parameter means that the FEV1 was lower at the end of the arm than at the beginning, while a positive number means that the FEV1 was higher at the end.

Outcome measures

Measure	Borage and Echium Seed Oils n=42 Participants Borage and echium seed oils will be taken for six weeks. Borage and Echium Seed Oils: 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 Oil Pills n=39 Participants Corn oil pills will be taken for six weeks. Corn oil pills: Corn oils pills will be taken three times per day for six weeks.
Lung Function	-.12 Percent change Standard Deviation 6.7	0.22 Percent change Standard Deviation 5.77

SECONDARY outcome

Timeframe: Measurements obtained at 2, 8, 14, and 20 weeks

Population: We analyzed all samples available, including from subjects who did not complete the entire protocol (i.e., 40 subjects crossed over and completed both arms, but 44 completed the corn oil and 44 completed the borage and echium arm, and the overlap was incomplete). Thus, the number of subjects differs from the total number of subjects per arm

Changes in plasma level of gamma linolenic acid (GLA), a major constituent of Borage oil, as a measure of compliance. This was calculated by the difference between the amount produced at the start of each arm and at the end of each arm (i.e., two values were obtained in each arm and used to calculate the difference, and the differences were compared as a delta-delta).

Outcome measures

Measure	Borage and Echium Seed Oils n=39 Participants Borage and echium seed oils will be taken for six weeks. Borage and Echium Seed Oils: 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 Oil Pills n=39 Participants Corn oil pills will be taken for six weeks. Corn oil pills: Corn oils pills will be taken three times per day for six weeks.
Plasma Level of Gamma Linolenic Acid (GLA)	6.11 ng Standard Deviation 10.2	-.25 ng Standard Deviation 2.32

SECONDARY outcome

Timeframe: two weeks

Population: We analyzed all samples available including those who did not complete both arms of the protocol. Therefore the number of subjects in the two arms are not identical.

All individuals will be genotyped at the LTC4S locus.

Outcome measures

Measure	Borage and Echium Seed Oils n=42 Participants Borage and echium seed oils will be taken for six weeks. Borage and Echium Seed Oils: 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 Oil Pills Corn oil pills will be taken for six weeks. Corn oil pills: Corn oils pills will be taken three times per day for six weeks.
Number of Subjects Bearing a Polymorphic Variant of LTC4 Synthase	10 participants	—

SECONDARY outcome

Timeframe: Assessed at 2, 8, 14, and 20 weeks

Population: We analyzed all samples available, including from subjects who did not complete the entire protocol (i.e., 40 subjects crossed over and completed both arms, but 44 completed the corn oil and 44 completed the borage and echium arm, and the overlap was incomplete). Thus, the number of subjects differs from the total number of subjects per arm

Changes in asthma control will be assessed via the Asthma Control Questionnaire (ACQ) at each visit. The ACQ is a 6-point questionnaire that reflects the degree of asthma activity. Each point is assigned a scale of 0-5, with 5 being the worst. Thus, the range is from 0 (no asthma symptoms) to 30 (severe asthma symptoms). For each arm, we generate two values (week 2 vs. week 8 and week 14 vs.week 20). These values are then averaged for each arm to obtain the final single value. A negative number implies improved symptoms.

Outcome measures

Measure	Borage and Echium Seed Oils n=42 Participants Borage and echium seed oils will be taken for six weeks. Borage and Echium Seed Oils: 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 Oil Pills n=39 Participants Corn oil pills will be taken for six weeks. Corn oil pills: Corn oils pills will be taken three times per day for six weeks.
Asthma Control	-.18 Change in ACQ points Standard Deviation 0.64	-.12 Change in ACQ points Standard Deviation .50

SECONDARY outcome

Timeframe: Assessed at 2, 8, 14, and 20 weeks

Population: We analyzed all samples available, including from subjects who did not complete the entire protocol (i.e., 40 subjects crossed over and completed both arms, but 44 completed the corn oil and 44 completed the borage and echium arm, and the overlap was incomplete). Thus, the number of subjects differs from the total number of subjects per arm

Secondary outcome measures include changes in concentrations of omega 3 fatty acids in cell pellets, indicating incorporation of botanical oil metabolites in cell membrane lipids.. This was calculated by the difference between the amount present at the start of each arm and at the end of each arm (i.e., two values were obtained in each arm and used to calculate the difference, and the differences were compared as a delta-delta).

Outcome measures

Measure	Borage and Echium Seed Oils n=37 Participants Borage and echium seed oils will be taken for six weeks. Borage and Echium Seed Oils: 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 Oil Pills n=37 Participants Corn oil pills will be taken for six weeks. Corn oil pills: Corn oils pills will be taken three times per day for six weeks.
Measure of EPA in Cell Pellets	.094 ng Standard Deviation 2.01	-0.02 ng Standard Deviation 2.10

SECONDARY outcome

Timeframe: Days 0, 42, 84, and 126

Population: Since this is a crossover study, 30 of 32 who completed the borage arm also completed the corn oil arm. The data presented reflect the effects of borage/echium versus corn oil for individuals with two wild type alleles (AA) versus those with one variant allele (CC or AC).

Differences in LTC4S activity while receiving borage/echium oils versus corn oil stratified by LTC4S genotype. We analyzed the genotype for 32 subjects for the borage arm and 30 subjects for the placebo arm.

Outcome measures

Measure	Borage and Echium Seed Oils n=42 Participants Borage and echium seed oils will be taken for six weeks. Borage and Echium Seed Oils: 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 Oil Pills n=39 Participants Corn oil pills will be taken for six weeks. Corn oil pills: Corn oils pills will be taken three times per day for six weeks.
Change in Activity of LTC4 Synthase Genotype AA	.95 ng/million cells Standard Deviation 11.3	-.10 ng/million cells Standard Deviation 7.83
Change in Activity of LTC4 Synthase Genotype AC or CC	18.0 ng/million cells Standard Deviation 18.5	11.7 ng/million cells Standard Deviation 25.9

SECONDARY outcome

Timeframe: 0, 42, 84, and 126 days

Population: We analyzed all samples available including subjects who did not complete the entire protocol. Therefore the number of subjects analyzed differs from the total number of subjects per arm.

FEV1 was measured in all subjects at the beginning and end of both study arms. Subjects were genotyped at LTC4S locus and those bearing at least one A to C polymorphism were compared with those bearing two A alleles.

Outcome measures

Measure	Borage and Echium Seed Oils n=42 Participants Borage and echium seed oils will be taken for six weeks. Borage and Echium Seed Oils: 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 Oil Pills n=39 Participants Corn oil pills will be taken for six weeks. Corn oil pills: Corn oils pills will be taken three times per day for six weeks.
Genotype-specific Differences in Change in Lung Function While Receiving Borage and Echium Oils Versus Corn Oil. Genotype AA	-.02 Liters Standard Deviation .23	-.02 Liters Standard Deviation .16
Genotype-specific Differences in Change in Lung Function While Receiving Borage and Echium Oils Versus Corn Oil. Genotype AC or CC	0.08 Liters Standard Deviation .25	.18 Liters Standard Deviation .22

Adverse Events

Borage and Echium Seed Oils

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Corn Oil Pills

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Borage and Echium Seed Oils n=42 participants at risk Borage and echium seed oils will be taken for six weeks. Borage and Echium Seed Oils: 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 Oil Pills n=38 participants at risk Corn oil pills will be taken for six weeks. Corn oil pills: Corn oils pills will be taken three times per day for six weeks.
Respiratory, thoracic and mediastinal disorders Shortness of breath	0.00% 0/42 • The study ran for 20 weeks and data were collected over that time frame.	2.6% 1/38 • Number of events 1 • The study ran for 20 weeks and data were collected over that time frame.
Respiratory, thoracic and mediastinal disorders Asthma deterioration	7.1% 3/42 • Number of events 3 • The study ran for 20 weeks and data were collected over that time frame.	2.6% 1/38 • Number of events 1 • The study ran for 20 weeks and data were collected over that time frame.
Gastrointestinal disorders Gastrointestinal distress	14.3% 6/42 • Number of events 6 • The study ran for 20 weeks and data were collected over that time frame.	5.3% 2/38 • Number of events 2 • The study ran for 20 weeks and data were collected over that time frame.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract infection	7.1% 3/42 • Number of events 3 • The study ran for 20 weeks and data were collected over that time frame.	2.6% 1/38 • Number of events 1 • The study ran for 20 weeks and data were collected over that time frame.
Skin and subcutaneous tissue disorders Skin rash	2.4% 1/42 • Number of events 1 • The study ran for 20 weeks and data were collected over that time frame.	0.00% 0/38 • The study ran for 20 weeks and data were collected over that time frame.
Nervous system disorders Headache	2.4% 1/42 • Number of events 1 • The study ran for 20 weeks and data were collected over that time frame.	0.00% 0/38 • The study ran for 20 weeks and data were collected over that time frame.
Gastrointestinal disorders Elevated liver enzymes	0.00% 0/42 • The study ran for 20 weeks and data were collected over that time frame.	2.6% 1/38 • Number of events 1 • The study ran for 20 weeks and data were collected over that time frame.

Additional Information

Dr. Joshua Boyce

Brigham and Women's Hospital

Phone: 617-525-1261

Email: jboyce@partners.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place