Asthma
Conditions
Keywords
Ginger, Dietary supplement
Brief summary
This is a randomized, double blind, placebo controlled study to study whether there are potential benefits of consuming ginger by individuals with asthma.
Detailed description
Presently an estimated 25.9 million Americans suffer from asthma and over half have at least one asthma attack per year. Recent studies found that 60% of moderate asthmatics and 70% of severe asthmatics report using complementary and alternative medicine (CAM) to self-treat their asthma symptoms.The exact mechanism of action of these agents is unclear but may involve attenuation of allergic response, anti-inflammatory and antioxidant effects, and/or direct effects on airway smooth muscle which are responsible for airway narrowing in asthma. Studies done in mouse models of asthma and directly on airway smooth muscle cells demonstrate that ginger blocks one of the critical inflammatory pathways in asthma and thus leads to reduced airway inflammation and relaxation of airway smooth muscle. Clinical trials with chronic oral ginger therapy in humans have demonstrated safe consumption of 2 grams per day for 28 days with demonstrated anti-inflammatory effects in colon cancer and inflammatory bowel diseases. Thus, the investigators hypothesize that oral ginger at a dose of 2 grams per day will reduce airway inflammation and will reduce serum levels of asthma related inflammatory markers.
Interventions
DRUGGinger Extract
2gm Capsule of Ginger extract
DRUGPlacebo
Matching Placebo
Sponsors
National Center for Complementary and Integrative Health (NCCIH)
Emily DiMango, MD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Double blind placebo controlled
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Men or women age 18 or older; 2. Treatment with inhaled corticosteroids (ICS) +/- long acting β-agonists/long acting muscarinics and montelukast; 3. Physician diagnosed asthma; 4. Forced expiratory volume (FEV1) ≥60% of predicted 5. Methacholine PC(20) \< 16 mg/ml if taking ICS and \< 8mg/ml if not taking ICS at Visit 2. 6. Non-smoker (e.g., tobacco, e-cigarette, marijuana) for ≥1 yr.; 7. ≤10 pack-year smoking history; 8. Suboptimal control of asthma as determined by a score \< 19 or less on the Asthma Control Test (ACT) at Screening Visit (Visit 1) and Randomization Visit (Visit 3).
Exclusion criteria
1. Other major chronic illnesses: Conditions which in the judgment of the study physician would interfere with participation in the study, e.g., non-skin cancer, uncontrolled diabetes mellitus, coronary artery disease, congestive heart failure, stroke, severe hypertension, renal failure, liver disorders, malabsorption disorders, immunodeficiency states, major neuropsychiatric disorder; 2. Cardiovascular problems: Myocardial infarction or stroke in last 3 months Uncontrolled hypertension Known aortic aneurysm 3. History of physician diagnosis of chronic bronchitis, emphysema or chronic obstructive pulmonary disease (COPD) 4. Medication use: Current consumption of ginger supplements, oral corticosteroid use within the past 6 weeks, use of an investigational treatment in the previous 30 days, known adverse reaction to ginger or ginger products; 5. Females of childbearing potential: Pregnant or lactating; participants of appropriate age who might be pregnant at the time of enrollment will be screened with urine pregnancy tests at each visit and cannot participate if pregnant. Participants must agree to use effective contraception during the trial. 6. Inability to perform acceptable and repeatable spirometry maneuvers throughout the test procedure.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Tolerance to Inhaled Methacholine | Baseline and Day 28 | A methacholine challenge test is a medical test used to assist in the diagnosis of asthma. The patient breathes in nebulized methacholine at gradually increasing doubling doses, starting with diluent only. Methacholine provokes bronchoconstriction, or narrowing of the airways via M3 receptors. The degree of narrowing can then be quantified by spirometry which is performed after inhalation of each dose. Methacholine provocation dose (PD)20 values will be used to measure any change in airway hyperresponsiveness. |
| Change in Fractional Exhaled Nitric Oxide (FeNO) | Baseline and Day 28 | Measure of markers of asthmatic lung inflammation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Serum Cytokines | Baseline and Day 56 | Measure of markers of asthmatic lung inflammation |
| Change in Eosinophilia | Baseline and Day 56 | Measure of markers of asthmatic lung inflammation |
| Change in Score on the Asthma Control Test (ACT) | Baseline and Day 56 | Asthma symptom score will be measured with the Asthma Control Test at Visit 1, 2 and 5.This instrument, which has been validated for ages 12-84 years, is a 4-week recall questionnaire that addresses issues of asthma control, symptoms, and nocturnal awakenings. The scores range from 5 (poor control of asthma) to 25 (complete control of asthma), with higher scores reflecting greater asthma control. An ACT score \>19 indicates well-controlled asthma. |
| Change In Score on Juniper Mini-Asthma Specific Quality of Life (Mini AQLQ-J) | Baseline and Day 56 | This questionnaire consists of 15 items in 4 domains with a 2-week recall period. Scores range from 7-105, with higher scores indicating better quality of life. |
Countries
United States
Participant flow
Pre-assignment details
54 participants were enrolled and 12 participants were excluded due to: lost to follow-up, asthma controlled, lung function below threshold, on exclusionary medications, and not taking asthma medications. Eight participants were withdrawn due to an institutional COVID-19 research pause.
Participants by arm
| Arm | Count |
|---|---|
| Active Drug Subjects assigned to the intervention will receive 2 grams daily of Ginger Extract for 56 days.
Ginger Extract: 2gm Capsule of Ginger extract | 20 |
| Placebo Subjects assigned to the placebo group will receive a matching placebo for 56 days.
Placebo: Matching Placebo | 12 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Active Drug | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 53.9 years STANDARD_DEVIATION 17.5 | 54.7 years STANDARD_DEVIATION 15.8 | 56.1 years STANDARD_DEVIATION 13 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 8 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 4 Participants | 5 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) White | 9 Participants | 12 Participants | 3 Participants |
| Region of Enrollment United States | 20 participants | 32 participants | 12 participants |
| Sex: Female, Male Female | 11 Participants | 18 Participants | 7 Participants |
| Sex: Female, Male Male | 9 Participants | 14 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 12 |
| other Total, other adverse events | 0 / 20 | 1 / 12 |
| serious Total, serious adverse events | 0 / 20 | 1 / 12 |
Outcome results
Primary
Change in Fractional Exhaled Nitric Oxide (FeNO)
Measure of markers of asthmatic lung inflammation
Time frame: Baseline and Day 56
Population: Nine placebo analyzed due to device malfunction.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Drug | Change in Fractional Exhaled Nitric Oxide (FeNO) | -4.6 fractional exhaled parts per billion | Standard Deviation 20.4 |
| Placebo | Change in Fractional Exhaled Nitric Oxide (FeNO) | 26.2 fractional exhaled parts per billion | Standard Deviation 62.6 |
Primary
Change in Fractional Exhaled Nitric Oxide (FeNO)
Measure of markers of asthmatic lung inflammation
Time frame: Baseline and Day 28
Population: Eight placebo analyzed due to device malfunction.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Drug | Change in Fractional Exhaled Nitric Oxide (FeNO) | 8.5 fractional exhaled parts per billion | Standard Deviation 26.9 |
| Placebo | Change in Fractional Exhaled Nitric Oxide (FeNO) | 20.1 fractional exhaled parts per billion | Standard Deviation 43.1 |
Primary
Change in Tolerance to Inhaled Methacholine
A methacholine challenge test is a medical test used to assist in the diagnosis of asthma. The patient breathes in nebulized methacholine at gradually increasing doubling doses, starting with diluent only. Methacholine provokes bronchoconstriction, or narrowing of the airways via M3 receptors. The degree of narrowing can then be quantified by spirometry which is performed after inhalation of each dose. Methacholine provocation dose (PD)20 values will be used to measure any change in airway hyperresponsiveness.
Time frame: Baseline and Day 28
Population: Nine active drug and seven placebo participants were analyzed due to: 1) low lung function at the time of the study visit (methacholine testing was withheld for safety reasons) and 2) during the COVID-19 pandemic, methacholine testing was discontinued, as it is an aerosol generating procedure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Drug | Change in Tolerance to Inhaled Methacholine | 5.3 mg/ml | Standard Deviation 15.1 |
| Placebo | Change in Tolerance to Inhaled Methacholine | 24.2 mg/ml | Standard Deviation 55.9 |
Primary
Change in Tolerance to Inhaled Methacholine
A methacholine challenge test is a medical test used to assist in the diagnosis of asthma. The patient breathes in nebulized methacholine at gradually increasing doubling doses, starting with diluent only. Methacholine provokes bronchoconstriction, or narrowing of the airways via M3 receptors. The degree of narrowing can then be quantified by spirometry which is performed after inhalation of each dose. Methacholine provocation dose (PD20) values will be used to measure any change in airway hyperresponsiveness.
Time frame: Baseline and Day 56
Population: Twelve active drug and three placebo participants were analyzed due to: 1) low lung function at the time of the study visit (methacholine testing was withheld for safety reasons) and 2) during the COVID-19 pandemic, methacholine testing was discontinued, as it is an aerosol generating procedure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Drug | Change in Tolerance to Inhaled Methacholine | 4 PD20 of methacholine (mg/ml) | Standard Deviation 13.1 |
| Placebo | Change in Tolerance to Inhaled Methacholine | 78.4 PD20 of methacholine (mg/ml) | Standard Deviation 137.9 |
Secondary
Change in Eosinophilia
Measure of markers of asthmatic lung inflammation
Time frame: Baseline and Day 56
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Drug | Change in Eosinophilia | 0.007 x10^9 cells/L | Standard Deviation 0.219 |
| Placebo | Change in Eosinophilia | 0.128 x10^9 cells/L | Standard Deviation 0.211 |
Secondary
Change In Score on Juniper Mini-Asthma Specific Quality of Life (Mini AQLQ-J)
This questionnaire consists of 15 items in 4 domains with a 2-week recall period. Scores range from 7-105, with higher scores indicating better quality of life.
Time frame: Baseline and Day 56
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Drug | Change In Score on Juniper Mini-Asthma Specific Quality of Life (Mini AQLQ-J) | -11.3 score on a scale | Standard Deviation 21.91 |
| Placebo | Change In Score on Juniper Mini-Asthma Specific Quality of Life (Mini AQLQ-J) | -11.5 score on a scale | Standard Deviation 13.01 |
Secondary
Change in Score on the Asthma Control Test (ACT)
Asthma symptom score will be measured with the Asthma Control Test at Visit 1, 2 and 5.This instrument, which has been validated for ages 12-84 years, is a 4-week recall questionnaire that addresses issues of asthma control, symptoms, and nocturnal awakenings. The scores range from 5 (poor control of asthma) to 25 (complete control of asthma), with higher scores reflecting greater asthma control. An ACT score \>19 indicates well-controlled asthma.
Time frame: Baseline and Day 56
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Drug | Change in Score on the Asthma Control Test (ACT) | -1.6 score on a scale | Standard Deviation 3.966 |
| Placebo | Change in Score on the Asthma Control Test (ACT) | -2.0 score on a scale | Standard Deviation 2.045 |
Secondary
Change in Serum Cytokines
Measure of markers of asthmatic lung inflammation
Time frame: Baseline and Day 56
Population: Cytokine samples were collected from 15 and 10 active and placebo participants respectively.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Drug | Change in Serum Cytokines | -1.297 pg/ml | Standard Deviation 18.81 |
| Placebo | Change in Serum Cytokines | 2.411 pg/ml | Standard Deviation 18.81 |