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| ID | Type | Description | Link |
|---|---|---|---|
| UL1RR024146 | U.S. NIH Grant/Contract | View source | |
| K30-04-Z001 | Other Identifier | UC Davis |
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| Name | Class |
|---|---|
| National Institutes of Health (NIH) | NIH |
| National Center for Research Resources (NCRR) | NIH |
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Nitric oxide is an important marker of airway inflammation in asthma. Nitric oxide may have a protective role in patients with moderate to severe asthma. The investigators believe that a natural amino acid, L-arginine, that augments nitric oxide levels can decrease asthma exacerbations and improve the asthma care of moderate to severe asthma patients.
This study is a randomized, placebo controlled trial in which subjects will receive either 3 months of L-arginine supplementation or a placebo. The investigators will monitor subjects' symptoms, the number of asthma exacerbations, and lung function. In addition, we will draw blood, obtain induced sputum samples and measure exhaled breath nitric oxide levels at each monthly visit.
The primary objective of this 3 month clinical study is to determine if supplemental L-arginine can decrease the number of asthma exacerbations in patients with severe asthma. L-arginine, a natural amino acid, produces nitric oxide (NO) when it is converted to L-citrulline in the presence of the nitric oxide synthase enzymes. We and others have found that NO can protect against allergic airway inflammation, airway hyperresponsiveness and airway fibrosis in various animal models. In addition, we have found that arginase I expression correlates strongly with the lymphocyte and eosinophil influx into the lung and this enzyme may regulate the airway inflammatory response. Our central hypothesis is that L-arginine will increase NO levels in the lung and decrease the number of acute exacerbations of asthma. It may do this by either decreasing the number of Th2 lymphocytes or down-regulating arginase I expression or both.
Our specific aims are, therefore,
Patients will be recruited primarily from the UC Davis Asthma Network (UCAN) clinics, which focus on the care of severe asthmatics, and the study will be performed at the UC Davis/VA General Clinical Research Center.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arginine | Active Comparator | Enrolled subjects will take L-arginine orally, at 0.1 g/kg/day. Subjects will take three to four 1 g capsules (based on weight) of L-arginine twice daily for three months. L-arginine capsules were obtained from Jarrow Pharmaceuticals. |
|
| Placebo | Placebo Comparator | Enrolled subjects took three to four placebo capsules that matched color and size of the intervention twice daily for three months. Matching placebo capsules were obtained from Jarrow Pharmaceuticals. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| L-arginine | Drug | subjects will take matching 0.01 g/kg/day of L-arginine in divided doses for thre months. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Asthma Exacerbations in Three Months | Asthma exacerbation is a composite endpoint. An asthma exacerbation is defined as any of the following: a) a drop in the morning peak expiratory flow rate (PEF) >30% from baseline on 2 consecutive days, b) a need for initiation of or increased dose of inhaled corticosteroids, or the c) doubling of short-acting rescue β-agonist drug use (e.g.Albuterol) on two consecutive days. Any one of these three counts as one asthma exacerbation. | 3 months |
| Measure | Description | Time Frame |
|---|---|---|
| L-arginine Serum Concentration | 90 days |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Nicholas Kenyon, MD | University of California, Davis | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California, Davis General Clinical Research Center | Sacramento | California | 95817 | United States |
The randomization process and disbursement of L-arginine (0.05 g/kg twice daily; 6-10 g/day) and placebo were done by the UC Davis Investigational Drug Service.Eligible subjects had documented moderate to severe persistent asthma, were at least 18 years of age, not pregnant, and able to give consent.
Between 2006-2008, moderate to severe persistent asthma patients, as defined by the NAEPP Expert Panel Reports, were eligible for enrollment [10]. Most subjects were recruited from the UC Davis Asthma Network clinics, which are referral clinics for patients with difficult to control asthma.
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| ID | Title | Description |
|---|---|---|
| FG000 | Arginine | 2.3. L-Arginine Intervention The randomization process and disbursement of L-arginine and placebo were done by the UC Davis Investigational Drug Service to ensure that both the physician and participant were blinded. |
| FG001 | Placebo | 2.3. L-Arginine Intervention The randomization process and disbursement of L-arginine and placebo were done by the UC Davis Investigational Drug Service to ensure that both the physician and participant were blinded. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Arginine | 2.3. L-Arginine Intervention The randomization process and disbursement of L-arginine (0.05 g/kg twice daily; 6-10 g/day) and placebo were done by the UC Davis Investigational Drug Service to ensure that both the physician and participant were blinded. The subjects began the study medication on day 0 and continued for 90 days and were asked to discontinue use of any nutritional supplements prior to the start of the study. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| 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 | Number of Asthma Exacerbations in Three Months | Asthma exacerbation is a composite endpoint. An asthma exacerbation is defined as any of the following: a) a drop in the morning peak expiratory flow rate (PEF) >30% from baseline on 2 consecutive days, b) a need for initiation of or increased dose of inhaled corticosteroids, or the c) doubling of short-acting rescue β-agonist drug use (e.g.Albuterol) on two consecutive days. Any one of these three counts as one asthma exacerbation. | Our original power analysis was based on an expected minor exacerbation rate of 3-4 per month. | Posted | Number | exacerbations | 3 months |
|
1 year intervals
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arginine | L-arginine 1 g tablets were made by Jarrow Formulas. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypertension | Cardiac disorders | Non-systematic Assessment | One subject in the placebo group was unblinded from the study and discontinued from study drug because of an increased in blood pressure. Blood pressure returned to normal. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Nicholas Kenyon | UCaliforniaDavis | 916-734-3564 | njkenyon@ucdavis.edu |
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| ID | Term |
|---|---|
| D001249 | Asthma |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
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| ID | Term |
|---|---|
| D001120 | Arginine |
| ID | Term |
|---|---|
| D024361 | Amino Acids, Basic |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| D000599 | Amino Acids, Diamino |
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| Placebo | Drug | Placebo tablets that match the L-arginine intervention tablets will be given for three months |
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|
| BG001 | Placebo | Placebo intervention |
| BG002 | Total | Total of all reporting groups |
| Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| FEV1 Percent Predicted | Mean | Standard Deviation | Percent |
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| Exhaled Nitric oxide | The secondary clinical endpoints that were measured included the patient symptom diary, daily short acting β-agonist use, St. George's Respiratory questionnaire, daily PEF diary, forced expiratory volume in one second (FEV1), and forced expiratory volume in one second to forced vital capacity ratio (FEV1/FVC) measurements performed at the monthly visits, exhaled NO concentration and induced sputum eosinophil percent counts | Mean | Standard Deviation | ppb (parts per billion) |
|
| Placebo |
Matching placebo tablets were made by Jarrow Formulas. |
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| Secondary | L-arginine Serum Concentration | Posted | Mean | Standard Error | pmol/100ul | 90 days |
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| 0 |
| 10 |
| 0 |
| 10 |
| EG001 | Placebo | Matching placebo tablets were purchased from Jarrow Formulas. | 0 | 10 | 1 | 10 |
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| D012130 |
| Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| D000601 | Amino Acids, Essential |