Asthma, Obesity
Conditions
Brief summary
A 14-week, randomized, placebo-controlled, double-masked clinical trial in 40 obese patients with poorly controlled asthma. The intervention is Mitoquinol (MitoQ) versus placebo. The primary aim of this pilot study is to determine if MitoQ improves airway reactivity in obese patients with asthma.
Detailed description
Study aim: The objective of this proposal is to conduct a pilot clinical trial to determine if the mitochondrial-targeted anti-oxidant MitoQ improves airway reactivity in obese patients with poorly controlled asthma. Type of Study: A 14 weeks, prospective, two center (Duke and the University of Vermont), randomized, placebo-controlled, double-masked clinical trial. Study Population: 40 patients with obesity and poorly controlled asthma. Intervention: MitoQ 40 mg per day versus placebo.
Interventions
DRUGMitoquinol
Mitoquinol (MitoQ) 40 mg per day for 12 weeks
DRUGPlacebo oral tablet
Placebo daily for 12 weeks
Sponsors
Duke University
University of Vermont
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Double masked study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. participant reported physician diagnosis of asthma 2. participant reported on regular prescribed controller therapy for at least 3 months 3. positive methacholine challenge (as determined by spirometry PD20 or oscillometry PD50 ≤ 4.0 mg/ml at visit 2) 4. age: ≥18 years 5. BMI ≥ 30 kg/m2 (at visit 1) 6. poorly controlled asthma defined as one of the following: 1. Asthma Control Test5 Score ≤ 19 (at visit 1), or 2. Participant reported use of rescue inhaler on average \> 2 uses/week for preceding month, or 3. Participant reported nocturnal asthma awakening on average 1 or more times / week in preceding month, or 4. Participant reported ED/hospital visit or prednisone course for asthma in past six months 7. ability and willingness to provide informed consent
Exclusion criteria
1. participant reported use of an investigational agent in the prior 30 days 2. participant reported physician diagnosis of chronic obstructive pulmonary disease 3. pregnancy and/or participant reported lactation 4. females of childbearing age who do not agree to practice an adequate birth control method for the duration of the study (abstinence, combination barrier and spermicide, or hormonal) 5. participant reported greater than 10 pack year smoking history 6. participant reported smoking conventional tobacco products (cigar, cigarette, & pipes) within the last 6 months 7. participant reported e-cigarette use more than 2x/week 8. participant unwilling to withhold e-cigarette use for the duration of the study 9. participant reported vaping more than 2x/week 10. participant unwilling to withhold vaping for the duration of the study 11. participant reported marijuana use (inhalation) more than 2x/week 12. participant unwilling to withhold marijuana use (inhalation) for the duration of the study 13. participant reported sinus surgery performed ≤ 4 weeks from visit 1 14. participant reported eye surgery within the prior 3 months 15. participant reported use of the antioxidants idebenone or co-enzyme Q10 within 8 weeks 16. participant reported tendency to develop severe nose bleeds 17. FEV1 ˂ 60% predicted or \< 1.5 Liters at visit 1 18. participant reported treatment for asthma exacerbation in the previous 4 weeks 19. participant was not able to complete at least 50% of the days on the diary cards returned at visit 2 20. other significant disease that in the opinion of the investigator would interfere with the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Airway Reactivity | Through study completion, 12 weeks | change in airway reactivity, measured by change in the concentration of methacholine producing a 20 % decrease in forced expiratory volume in one second, from baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Asthma Control Test (ACT) | Through study completion, 12 weeks | To collect data on asthma symptoms measured by asthma control questionnaire with units on a scale from 5-25 (the lower the score, the worse the asthma symptoms) |
| Number of Participants With Adherence at 12 Weeks | Through study completion, 12 weeks | Adherence determined from pill counts (classified as adherent if used at least 80% of predicted pills) |
| Change in Asthma Quality of Life Questionnaire Score | Through study completion, 12 weeks | The Marks Asthma Quality of Life Questionnaire (Marks AQLQ). units on a scale from 1 to 5. Higher score indicates better quality of life |
| Change in FEV1 | Through study completion, 12 weeks | Change in forced expiratory volume in one second between baseline and 12 week visit |
| Change in FVC | Through study completion, 12 weeks | Change in forced vital capacity from baseline to 12 weeks measured in liters |
Countries
United States
Participant flow
Recruitment details
Recruitment period 1/1/2020-12/1/2023 Recruitment locations: two pulmonary clinics at academic medical centers in the U.S.
Pre-assignment details
Run in period after screening prior to randomization 9 participants excluded 6 screen fails (2 low lung function, 3 negative methacholine, 1 unable to perform study procedures 3 withdrew (1 lack of transport, 2 research burden)
Participants by arm
| Arm | Count |
|---|---|
| MitoQ MitoQ 40 mg per day for 12 weeks | 20 |
| Placebo placebo daily for 12 weeks | 18 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | mental health crisis | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | MitoQ | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 50 years STANDARD_DEVIATION 13 | 55 years STANDARD_DEVIATION 7 | 52 years STANDARD_DEVIATION 11 |
| Airway reactivity to methacholine | 44.5 μg methacholine | 113 μg methacholine | 110 μg methacholine |
| Asthma Control Test | 16.4 total score STANDARD_DEVIATION 5.2 | 16.3 total score STANDARD_DEVIATION 3.1 | 16.3 total score STANDARD_DEVIATION 4.2 |
| AX | 37.03 cm H20/L | 59.06 cm H20/L | 42.61 cm H20/L |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants | 18 Participants | 38 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| FEV1 | 2.45 liters STANDARD_DEVIATION 0.74 | 2.32 liters STANDARD_DEVIATION 0.75 | 2.39 liters STANDARD_DEVIATION 0.74 |
| FVC | 3.48 liters STANDARD_DEVIATION 1.04 | 3.13 liters STANDARD_DEVIATION 0.95 | 3.30 liters STANDARD_DEVIATION 1.03 |
| Marks Asthma Quality of Life | 2.19 score on questionnaire STANDARD_DEVIATION 0.98 | 2.27 score on questionnaire STANDARD_DEVIATION 0.76 | 2.23 score on questionnaire STANDARD_DEVIATION 0.87 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 5 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 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 | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 14 Participants | 13 Participants | 27 Participants |
| Region of Enrollment United States | 20 Participants | 18 Participants | 38 Participants |
| Sex: Female, Male Female | 14 Participants | 15 Participants | 29 Participants |
| Sex: Female, Male Male | 6 Participants | 3 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 18 |
| other Total, other adverse events | 12 / 20 | 10 / 18 |
| serious Total, serious adverse events | 0 / 20 | 0 / 18 |
Outcome results
Primary
Change in Airway Reactivity
change in airway reactivity, measured by change in the concentration of methacholine producing a 20 % decrease in forced expiratory volume in one second, from baseline
Time frame: Through study completion, 12 weeks
Population: 2 participants in the MitoQ group withdrew 4 participants in the placebo group did not perform methacholine at 12 week visit: Lung function too low (FEV1 less than 60%), and participants unable to complete testing
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MitoQ | Change in Airway Reactivity | 0 μg methacholine |
| Placebo | Change in Airway Reactivity | -0.8 μg methacholine |
p-value: 0.81Wilcoxon rank sum
Secondary
Change in Asthma Control Test (ACT)
To collect data on asthma symptoms measured by asthma control questionnaire with units on a scale from 5-25 (the lower the score, the worse the asthma symptoms)
Time frame: Through study completion, 12 weeks
Population: 2 withdrew from mitoQ group
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MitoQ | Change in Asthma Control Test (ACT) | 1 score |
| Placebo | Change in Asthma Control Test (ACT) | 1 score |
Secondary
Change in Asthma Quality of Life Questionnaire Score
The Marks Asthma Quality of Life Questionnaire (Marks AQLQ). units on a scale from 1 to 5. Higher score indicates better quality of life
Time frame: Through study completion, 12 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MitoQ | Change in Asthma Quality of Life Questionnaire Score | -0.08 questionnaire score |
| Placebo | Change in Asthma Quality of Life Questionnaire Score | -0.05 questionnaire score |
Secondary
Change in FEV1
Change in forced expiratory volume in one second between baseline and 12 week visit
Time frame: Through study completion, 12 weeks
Population: one participant unable to complete spirometry testing at 12 week visit
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MitoQ | Change in FEV1 | -0.01 liters |
| Placebo | Change in FEV1 | 0.03 liters |
Secondary
Change in FVC
Change in forced vital capacity from baseline to 12 weeks measured in liters
Time frame: Through study completion, 12 weeks
Population: one participant in the placebo group unable to perform lung function testing at 12 week visit
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MitoQ | Change in FVC | -0.01 liters |
| Placebo | Change in FVC | 0.01 liters |
Secondary
Number of Participants With Adherence at 12 Weeks
Adherence determined from pill counts (classified as adherent if used at least 80% of predicted pills)
Time frame: Through study completion, 12 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MitoQ | Number of Participants With Adherence at 12 Weeks | 15 Participants |
| Placebo | Number of Participants With Adherence at 12 Weeks | 12 Participants |