Trial Outcomes & Findings for L-arginine in Severe Asthma Patients Grouped by Exhaled Nitric Oxide Levels (NCT NCT01841281)
NCT ID: NCT01841281
Last Updated: 2020-04-21
Results Overview
The primary endpoint of the study is the number of acute moderate exacerbations at 3 months. A moderate asthma exacerbation is defined as any of the following: 1) A drop in morning peak flow rate (PEFR) \>30% from baseline on 2 consecutive days (1 event), 2) Need for initiation of oral steroids or am increased dose of inhaled corticosteroids on any two consecutive days (1 event), 3) Doubling of short-acting β-agonist use (e.g. number of puffs of albuterol) per day for 2 consecutive days (1 event).
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
54 participants
Primary outcome timeframe
3 month
Results posted on
2020-04-21
Participant Flow
54 subjects consented and enrolled for the trial, but n=50 were randomized as n=4 participants declined to participate.
Participants were assigned to low or high exhaled nitric oxide groups based on their levels at time of Visit 1.
Participant milestones
| Measure |
Low Exhaled Nitric Oxide (NO), L-Arginine First, Then Placebo
Subjects with a baseline exhaled NO level less than or equal to 20 ppb
Receive L-arginine first, then Placebo
L-Arginine: L-arginine tablets containing 1 g of elemental L-arginine (1204 mg of L-arginine HCL) developed by Jarrow Formulas in Los Angeles.
Placebo: Matching placebo tablets do not contain L-arginine. Placebo tablets were manufactured by Jarrow Formulas and contain cellulose and other excipients.
|
High Exhaled Nitric Oxide (NO), L-Arginine First, Then Placebo
Subjects with a baseline exhaled NO level greater than or equal to 25 ppb
Receive L-arginine first, then Placebo
L-Arginine: L-arginine tablets containing 1 g of elemental L-arginine (1204 mg of L-arginine HCL) developed by Jarrow Formulas in Los Angeles.
Placebo: Matching placebo tablets do not contain L-arginine. Placebo tablets were manufactured by Jarrow Formulas and contain cellulose and other excipients.
|
Low Exhaled Nitric Oxide (NO), Placebo First, Then L-Arginine
Subjects with a baseline exhaled NO level less than or equal to 20 ppb
Receive Placebo first, then L-arginine
L-Arginine: L-arginine tablets containing 1 g of elemental L-arginine (1204 mg of L-arginine HCL) developed by Jarrow Formulas in Los Angeles.
Placebo: Matching placebo tablets do not contain L-arginine. Placebo tablets were manufactured by Jarrow Formulas and contain cellulose and other excipients.
|
High Exhaled Nitric Oxide (NO), Placebo First, Then L-Arginine
Subjects with a baseline exhaled NO level greater than or equal to 25 ppb
Receive L-arginine first, then Placebo
L-Arginine: L-arginine tablets containing 1 g of elemental L-arginine (1204 mg of L-arginine HCL) developed by Jarrow Formulas in Los Angeles.
Placebo: Matching placebo tablets do not contain L-arginine. Placebo tablets were manufactured by Jarrow Formulas and contain cellulose and other excipients.
|
|---|---|---|---|---|
|
First Intervention (12 Weeks)
STARTED
|
11
|
12
|
13
|
14
|
|
First Intervention (12 Weeks)
COMPLETED
|
11
|
12
|
13
|
14
|
|
First Intervention (12 Weeks)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Washout (6 Weeks)
STARTED
|
11
|
12
|
13
|
14
|
|
Washout (6 Weeks)
COMPLETED
|
9
|
9
|
10
|
13
|
|
Washout (6 Weeks)
NOT COMPLETED
|
2
|
3
|
3
|
1
|
|
Second Intervention (12 Weeks)
STARTED
|
9
|
9
|
10
|
13
|
|
Second Intervention (12 Weeks)
COMPLETED
|
9
|
6
|
10
|
13
|
|
Second Intervention (12 Weeks)
NOT COMPLETED
|
0
|
3
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
L-arginine in Severe Asthma Patients Grouped by Exhaled Nitric Oxide Levels
Baseline characteristics by cohort
| Measure |
Low Exhaled Nitric Oxide (NO)
n=24 Participants
Subjects with a baseline exhaled NO level less than or equal to 20 ppb will be enrolled in the Low Exhaled Nitric Oxide arm.
Baseline characteristics at the enrollment
|
High Exhaled Nitric Oxide (NO)
n=26 Participants
Subjects with a baseline exhaled NO level greater than or equal to 25 ppb will be enrolled in the High Exhaled Nitric Oxide arm.
Baseline characteristics at the enrollment
|
Total
n=50 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
56.5 years
STANDARD_DEVIATION 11.9 • n=5 Participants
|
52.4 years
STANDARD_DEVIATION 14.3 • n=7 Participants
|
54.3 years
STANDARD_DEVIATION 13.2 • n=5 Participants
|
|
Sex: Female, Male
Female
|
17 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
38 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
19 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
39 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Non-White
|
5 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Spirometry
FEV1
|
1.8 Litters
STANDARD_DEVIATION 0.7 • n=5 Participants
|
2.2 Litters
STANDARD_DEVIATION 0.9 • n=7 Participants
|
2 Litters
STANDARD_DEVIATION 0.8 • n=5 Participants
|
|
Spirometry
FVC
|
2.6 Litters
STANDARD_DEVIATION 0.9 • n=5 Participants
|
2.8 Litters
STANDARD_DEVIATION 1.1 • n=7 Participants
|
2.7 Litters
STANDARD_DEVIATION 1.0 • n=5 Participants
|
|
Weight
|
94.8 Kg
STANDARD_DEVIATION 20.5 • n=5 Participants
|
85.6 Kg
STANDARD_DEVIATION 27.3 • n=7 Participants
|
90.0 Kg
STANDARD_DEVIATION 24.5 • n=5 Participants
|
|
Asthma Control Test Score
|
16.0 units on a scale
STANDARD_DEVIATION 4.6 • n=5 Participants
|
16.1 units on a scale
STANDARD_DEVIATION 5.5 • n=7 Participants
|
16.1 units on a scale
STANDARD_DEVIATION 5.0 • n=5 Participants
|
PRIMARY outcome
Timeframe: 3 monthPopulation: Several patients dropped after the first intervention
The primary endpoint of the study is the number of acute moderate exacerbations at 3 months. A moderate asthma exacerbation is defined as any of the following: 1) A drop in morning peak flow rate (PEFR) \>30% from baseline on 2 consecutive days (1 event), 2) Need for initiation of oral steroids or am increased dose of inhaled corticosteroids on any two consecutive days (1 event), 3) Doubling of short-acting β-agonist use (e.g. number of puffs of albuterol) per day for 2 consecutive days (1 event).
Outcome measures
| Measure |
Low Exhaled Nitric Oxide (NO), L-Arginine First, Then Placebo
n=11 Participants
Subjects with a baseline exhaled NO level less than or equal to 20 ppb
Receive L-arginine first, then Placebo
L-Arginine: L-arginine tablets containing 1 g of elemental L-arginine (1204 mg of L-arginine HCL) developed by Jarrow Formulas in Los Angeles.
Placebo: Matching placebo tablets do not contain L-arginine. Placebo tablets were manufactured by Jarrow Formulas and contain cellulose and other excipients.
|
High Exhaled Nitric Oxide (NO), L-Arginine First, Then Placebo
n=12 Participants
Subjects with a baseline exhaled NO level greater than or equal to 25 ppb
Receive L-arginine first, then Placebo
L-Arginine: L-arginine tablets containing 1 g of elemental L-arginine (1204 mg of L-arginine HCL) developed by Jarrow Formulas in Los Angeles.
Placebo: Matching placebo tablets do not contain L-arginine. Placebo tablets were manufactured by Jarrow Formulas and contain cellulose and other excipients.
|
Low Exhaled Nitric Oxide (NO), Placebo First, Then L-Arginine
n=13 Participants
Subjects with a baseline exhaled NO level less than or equal to 20 ppb
Receive Placebo first, then L-arginine
L-Arginine: L-arginine tablets containing 1 g of elemental L-arginine (1204 mg of L-arginine HCL) developed by Jarrow Formulas in Los Angeles.
Placebo: Matching placebo tablets do not contain L-arginine. Placebo tablets were manufactured by Jarrow Formulas and contain cellulose and other excipients.
|
High Exhaled Nitric Oxide (NO), Placebo First, Then L-Arginine
n=14 Participants
Subjects with a baseline exhaled NO level greater than or equal to 25 ppb
Receive L-arginine first, then Placebo
L-Arginine: L-arginine tablets containing 1 g of elemental L-arginine (1204 mg of L-arginine HCL) developed by Jarrow Formulas in Los Angeles.
Placebo: Matching placebo tablets do not contain L-arginine. Placebo tablets were manufactured by Jarrow Formulas and contain cellulose and other excipients.
|
|---|---|---|---|---|
|
Number of Acute Exacerbation at 3 Months
Second Intervention
|
2.1 Events
Standard Deviation 1.4
|
2.7 Events
Standard Deviation 4.2
|
2.2 Events
Standard Deviation 2.2
|
2.2 Events
Standard Deviation 2.8
|
|
Number of Acute Exacerbation at 3 Months
First Intervention
|
2.7 Events
Standard Deviation 2.0
|
2.2 Events
Standard Deviation 2.2
|
1.6 Events
Standard Deviation 1.8
|
2.2 Events
Standard Deviation 3.0
|
SECONDARY outcome
Timeframe: 3 monthPopulation: Several patients dropped after the first intervention
The secondary endpoint is the change in FEV1/FVC ratio at 3 months. This calcuation is a ratio between the volume of breath exhaled in the first second divided by the total amount of breath exhaled in a vital capacity maneuver. A normal ratio is usually \> 70%.
Outcome measures
| Measure |
Low Exhaled Nitric Oxide (NO), L-Arginine First, Then Placebo
n=11 Participants
Subjects with a baseline exhaled NO level less than or equal to 20 ppb
Receive L-arginine first, then Placebo
L-Arginine: L-arginine tablets containing 1 g of elemental L-arginine (1204 mg of L-arginine HCL) developed by Jarrow Formulas in Los Angeles.
Placebo: Matching placebo tablets do not contain L-arginine. Placebo tablets were manufactured by Jarrow Formulas and contain cellulose and other excipients.
|
High Exhaled Nitric Oxide (NO), L-Arginine First, Then Placebo
n=12 Participants
Subjects with a baseline exhaled NO level greater than or equal to 25 ppb
Receive L-arginine first, then Placebo
L-Arginine: L-arginine tablets containing 1 g of elemental L-arginine (1204 mg of L-arginine HCL) developed by Jarrow Formulas in Los Angeles.
Placebo: Matching placebo tablets do not contain L-arginine. Placebo tablets were manufactured by Jarrow Formulas and contain cellulose and other excipients.
|
Low Exhaled Nitric Oxide (NO), Placebo First, Then L-Arginine
n=13 Participants
Subjects with a baseline exhaled NO level less than or equal to 20 ppb
Receive Placebo first, then L-arginine
L-Arginine: L-arginine tablets containing 1 g of elemental L-arginine (1204 mg of L-arginine HCL) developed by Jarrow Formulas in Los Angeles.
Placebo: Matching placebo tablets do not contain L-arginine. Placebo tablets were manufactured by Jarrow Formulas and contain cellulose and other excipients.
|
High Exhaled Nitric Oxide (NO), Placebo First, Then L-Arginine
n=14 Participants
Subjects with a baseline exhaled NO level greater than or equal to 25 ppb
Receive L-arginine first, then Placebo
L-Arginine: L-arginine tablets containing 1 g of elemental L-arginine (1204 mg of L-arginine HCL) developed by Jarrow Formulas in Los Angeles.
Placebo: Matching placebo tablets do not contain L-arginine. Placebo tablets were manufactured by Jarrow Formulas and contain cellulose and other excipients.
|
|---|---|---|---|---|
|
Forced Expiratory Volume in One Second (FEV1)/Forced Vital Capacity (FVC)
First Intervention
|
-0.02 ratio
Standard Deviation 0.05
|
0.01 ratio
Standard Deviation 0.06
|
0.03 ratio
Standard Deviation 0.13
|
-0.03 ratio
Standard Deviation 0.04
|
|
Forced Expiratory Volume in One Second (FEV1)/Forced Vital Capacity (FVC)
Second Intervention
|
0.01 ratio
Standard Deviation 0.04
|
0.13 ratio
Standard Deviation 0.06
|
0.003 ratio
Standard Deviation 0.06
|
-0.04 ratio
Standard Deviation 0.10
|
Adverse Events
Low Exhaled Nitric Oxide (NO) Phase 1, Treatment Arm
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Low Exhaled Nitric Oxide (NO) Phase 1, Placebo Arm
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Low Exhaled Nitric Oxide (NO) Washout Phase
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Low Exhaled Nitric Oxide (NO) Phase 2, Treatment Arm
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Low Exhaled Nitric Oxide (NO) Phase 2, Placebo Arm
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
High Exhaled Nitric Oxide (NO) Phase 1, Treatment Arm
Serious events: 2 serious events
Other events: 1 other events
Deaths: 0 deaths
High Exhaled Nitric Oxide (NO) Phase 1, Placebo Arm
Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths
High Exhaled Nitric Oxide (NO) Washout Phase
Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths
High Exhaled Nitric Oxide (NO) Phase 2, Treatment Arm
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
High Exhaled Nitric Oxide (NO) Phase 2, Placebo Arm
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Low Exhaled Nitric Oxide (NO) Phase 1, Treatment Arm
n=11 participants at risk
ow Exhaled Nitric Oxide (NO) Phase 1, L-Arginine arm
|
Low Exhaled Nitric Oxide (NO) Phase 1, Placebo Arm
n=13 participants at risk
Low Exhaled Nitric Oxide (NO) Phase 1, placebo arm
|
Low Exhaled Nitric Oxide (NO) Washout Phase
n=19 participants at risk
Low Exhaled Nitric Oxide (NO) Washout Phase
|
Low Exhaled Nitric Oxide (NO) Phase 2, Treatment Arm
n=10 participants at risk
Low Exhaled Nitric Oxide (NO) Phase 2, L-Arginine arm
|
Low Exhaled Nitric Oxide (NO) Phase 2, Placebo Arm
n=9 participants at risk
Low Exhaled Nitric Oxide (NO) Phase 2, placebo arm
|
High Exhaled Nitric Oxide (NO) Phase 1, Treatment Arm
n=12 participants at risk
High Exhaled Nitric Oxide (NO) Phase 1, L-Arginine arm
|
High Exhaled Nitric Oxide (NO) Phase 1, Placebo Arm
n=14 participants at risk
High Exhaled Nitric Oxide (NO) Phase 1, placebo arm
|
High Exhaled Nitric Oxide (NO) Washout Phase
n=22 participants at risk
High Exhaled Nitric Oxide (NO) Washout Phase
|
High Exhaled Nitric Oxide (NO) Phase 2, Treatment Arm
n=16 participants at risk
High Exhaled Nitric Oxide (NO) Phase 2, L-Arginine arm
|
High Exhaled Nitric Oxide (NO) Phase 2, Placebo Arm
n=6 participants at risk
igh Exhaled Nitric Oxide (NO) Phase 2, Placebo arm
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Hospitalization
|
0.00%
0/11 • Adverse events were collected for the duration of the trial,8 months
|
0.00%
0/13 • Adverse events were collected for the duration of the trial,8 months
|
0.00%
0/19 • Adverse events were collected for the duration of the trial,8 months
|
0.00%
0/10 • Adverse events were collected for the duration of the trial,8 months
|
0.00%
0/9 • Adverse events were collected for the duration of the trial,8 months
|
16.7%
2/12 • Number of events 2 • Adverse events were collected for the duration of the trial,8 months
|
7.1%
1/14 • Number of events 1 • Adverse events were collected for the duration of the trial,8 months
|
4.5%
1/22 • Number of events 1 • Adverse events were collected for the duration of the trial,8 months
|
0.00%
0/16 • Adverse events were collected for the duration of the trial,8 months
|
0.00%
0/6 • Adverse events were collected for the duration of the trial,8 months
|
Other adverse events
| Measure |
Low Exhaled Nitric Oxide (NO) Phase 1, Treatment Arm
n=11 participants at risk
ow Exhaled Nitric Oxide (NO) Phase 1, L-Arginine arm
|
Low Exhaled Nitric Oxide (NO) Phase 1, Placebo Arm
n=13 participants at risk
Low Exhaled Nitric Oxide (NO) Phase 1, placebo arm
|
Low Exhaled Nitric Oxide (NO) Washout Phase
n=19 participants at risk
Low Exhaled Nitric Oxide (NO) Washout Phase
|
Low Exhaled Nitric Oxide (NO) Phase 2, Treatment Arm
n=10 participants at risk
Low Exhaled Nitric Oxide (NO) Phase 2, L-Arginine arm
|
Low Exhaled Nitric Oxide (NO) Phase 2, Placebo Arm
n=9 participants at risk
Low Exhaled Nitric Oxide (NO) Phase 2, placebo arm
|
High Exhaled Nitric Oxide (NO) Phase 1, Treatment Arm
n=12 participants at risk
High Exhaled Nitric Oxide (NO) Phase 1, L-Arginine arm
|
High Exhaled Nitric Oxide (NO) Phase 1, Placebo Arm
n=14 participants at risk
High Exhaled Nitric Oxide (NO) Phase 1, placebo arm
|
High Exhaled Nitric Oxide (NO) Washout Phase
n=22 participants at risk
High Exhaled Nitric Oxide (NO) Washout Phase
|
High Exhaled Nitric Oxide (NO) Phase 2, Treatment Arm
n=16 participants at risk
High Exhaled Nitric Oxide (NO) Phase 2, L-Arginine arm
|
High Exhaled Nitric Oxide (NO) Phase 2, Placebo Arm
n=6 participants at risk
igh Exhaled Nitric Oxide (NO) Phase 2, Placebo arm
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
0.00%
0/11 • Adverse events were collected for the duration of the trial,8 months
|
7.7%
1/13 • Number of events 1 • Adverse events were collected for the duration of the trial,8 months
|
0.00%
0/19 • Adverse events were collected for the duration of the trial,8 months
|
0.00%
0/10 • Adverse events were collected for the duration of the trial,8 months
|
0.00%
0/9 • Adverse events were collected for the duration of the trial,8 months
|
8.3%
1/12 • Number of events 1 • Adverse events were collected for the duration of the trial,8 months
|
0.00%
0/14 • Adverse events were collected for the duration of the trial,8 months
|
0.00%
0/22 • Adverse events were collected for the duration of the trial,8 months
|
0.00%
0/16 • Adverse events were collected for the duration of the trial,8 months
|
0.00%
0/6 • Adverse events were collected for the duration of the trial,8 months
|
|
Skin and subcutaneous tissue disorders
Hives
|
0.00%
0/11 • Adverse events were collected for the duration of the trial,8 months
|
0.00%
0/13 • Adverse events were collected for the duration of the trial,8 months
|
0.00%
0/19 • Adverse events were collected for the duration of the trial,8 months
|
10.0%
1/10 • Number of events 1 • Adverse events were collected for the duration of the trial,8 months
|
0.00%
0/9 • Adverse events were collected for the duration of the trial,8 months
|
0.00%
0/12 • Adverse events were collected for the duration of the trial,8 months
|
0.00%
0/14 • Adverse events were collected for the duration of the trial,8 months
|
0.00%
0/22 • Adverse events were collected for the duration of the trial,8 months
|
0.00%
0/16 • Adverse events were collected for the duration of the trial,8 months
|
0.00%
0/6 • Adverse events were collected for the duration of the trial,8 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place