Asthma
Conditions
Keywords
Asthma, Biofeedback, Heart rate variability biofeedback, Inhaled corticosteroids
Brief summary
The goal of this research study to see whether biofeedback therapy helps treat asthma, and if so, how it works. Biofeedback is a treatment method that can teach how to bodily control. Biofeedback is widely used to help people relax. In this study however, the investigators want to learn if a specific type of biofeedback actually improves asthma in a way that might allow the reduction or elimination of other controller treatments like inhaled-corticosteroids.
Detailed description
The purpose of this study is to determine the role of Heart rate variability biofeedback (HRV-BF) in asthma management as either a controller (alternative) or bronchodilator (complementary) treatment, with respect to the current treatment of choice, inhaled corticosteroid (ICS) therapy, using different methods from participants that demonstrated clinically significant improvement in asthma outcomes in the investigator's previous research (1), and adding a second site not involved in the investigator's previous work. Inflammation of airways is viewed as the core pathophysiologic process in asthma. It is thought to render airways more reactive, and therefore, more susceptible to bronchoconstriction, leading to asthma exacerbations. Asthma is an episodic disease, where the goal of therapy is to reduce susceptibility to exacerbations, which may cause severe, even life-threatening illness. Anti-inflammatory medications reduce airways reactivity, while bronchodilator medications primarily relieve symptoms once an asthma exacerbation is in process, and may stop progressive constriction of airway smooth muscles (ASM). An anti-inflammatory effect of HRV-BF would have important implications for asthma management because adherence to ICS regimens is low due to a significant degree to feared side effects of prolonged steroid medication. Even if HRV-BF is found to only allow partial reduction in ICS requirements, this still would likely represent a major advance in asthma care.
Interventions
BEHAVIORALHeart rate variability biofeedback
Biofeedback teaches voluntary control of physiological functions by providing instantaneous feedback of variations in that bodily activity. Feedback usually is given in the form of visual and/or auditory signals derived from physiological recording devices. Among its salutary effects is a sense of medical self-efficacy, i.e., less dependency on medical professionals for maintaining personal health. The HRV-BF protocol we have developed and propose to examine herein works by a different pathway. It involves teaching the individual to increase the amplitude of heart rate accelerations during inhalation and de-celerations during exhalation, thus increasing the amplitude of respiratory sinus arrhythmia (RSA).
BEHAVIORALPlacebo
The method consists of: 1) receiving EEG/music biofeedback (actually, a mildly relaxing intervention, using EEG biofeedback to alternately increase and decrease frontal/occipital EEG alpha rhythms while listening to relaxing music), and 2) listening to recorded sounds of nature along with relaxing music with instructions to maintain a condition of relaxed alertness. For home training, subjects will be given placebo StressEraser programmed to give feedback to maintain their breathing at baseline rate.
Sponsors
Rutgers University
National Jewish Health
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Fred Wamboldt, MD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Mild to moderate persistent asthma for at least the past one year * Patients must not have taken oral or inhaled anti-inflammatory agents, including ICS and leukotriene inhibitors, for at least one month prior to study entry; and anti-IgE medications at least the past six months. Documented use of inhaled short-acting or long-acting β2-agonists during the month prior to study entry is, however, required. Xanthines, long-acting anticholinergics, and long-acting β2-agonists must be withdrawn within 72 hours upon entering the screening phase; short acting anticholinergics must be withdrawn within 48 hours before entering the screening phase. Patients will be required to abstain from these medications for the duration of study participation. * FEV1 values must be ≥60% of predicted normal values following a 6 hour albuterol withhold, and reversibility of FEV1 of at least 12% (equal to or greater than 200 cc) following up to four puffs of albuterol must occur; or asthma physician at study site must state based on medical history, exam, and spirometry data that patient has presumptive mild-moderate persistent asthma. * Lack of current asthma control as evidenced by ACT ≤ 19, or rescue use of B2-agonist ≥ 2/week within past 2 weeks, or waking due to asthma ≥ 1/week within past 2 weeks. * Patients must be non-smokers for at least the past year and have less than a 15 pack-year smoking history. This will minimize the risk of co-occurring COPD * Behavioral/linguistic competence: Ability to complete questionnaires and assessments in English * Patients must give informed consent prior to any study procedures.
Exclusion criteria
* Diagnosis of severe persistent asthma * 2 or more inpatient hospitalizations in the past year for asthma exacerbations; * History of only seasonal asthma * Patients with serious concomitant disease * Patients who have had a respiratory tract infection within 4 weeks of screening * Patients with a history of chronic bronchitis, COPD, or emphysema * Patients with a history of alcohol or drug abuse, or emotional or cognitive problems requiring psychotropic medication or likely to interfere procedural and treatment adherence * Any other clinically relevant deviation from normal in general medical history, physical examination, or laboratory parameters that would limit participation or interfere with study procedures and/or data collection; * Presence of exclusive extra-thoracic airway dysfunction * Women who are pregnant * Presence of a heart rhythm or other abnormality of heart rhythm on screening EKG that could preclude ac-curate HRV assessment * Chronically taking any medication likely to affect the autonomic or respiratory systems * Asthma therapy and concomitant medication * Previous participation in an investigational drug trial within 30 days prior to screening. * Concurrent participation in any other clinical trial or observational study at any time in the study. * Planning to move away from the area within the next 4 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Magnitude Change of Airway Reactivity Measured by Methacholine PC20FEV1 | 4-weeks | Change in PEC20FEV1 measured after biofeedback from the PC20FEV1 measured at baseline |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| HRV Biofeedback Biofeedback to maximaize heart rate variability. Procedure detailed in Lehrer, P. M., Vaschillo, B., Zucker, T., Graves, J., Katsamanis, M.,Aviles, M., & Wamboldt, F. S. (2013). Protocol for heart rate variability biofeedback training. Biofeedback, 41(3), 98-109. | 35 |
| EEG+ Biofeedback Included instructions to increase and decrease EEG alpha from the right frontal to occipital areas (F4 to Oz), to listen regularly to relaxing music and to do paced breathing at the baseline rate of spontaneous breathing observed during a nondemanding task. Procedure detailed in Lehrer, P. M., Hochron, S. M., Mayne, T., Isenberg, S., Carlson, V., Lasoski, A. M., … Rausch, L. (1994). Relaxation and music therapies for asthma among patients prestabilized on asthma medication. Journal of Behavioral Medicine, 17(1), 1-24. | 33 |
| Total | 68 |
Baseline characteristics
| Characteristic | HRV Biofeedback | EEG+ Biofeedback | Total |
|---|---|---|---|
| Age, Continuous | 38 years | 31 years | 34 years |
| Asthma Control Test (ACT) score total | 20 units on a scale | 20 units on a scale | 20 units on a scale |
| Baseline provocative conc causing 20% fall in forced expiratory volume in 1 sec (PC20FEV1) (mg/ml) | 1.66 mg/ml | 1.40 mg/ml | 1.46 mg/ml |
| Body Mass Index (BMI) | 28.53 kg/m^2 | 27.41 kg/m^2 | 28.27 kg/m^2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 8 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 31 Participants | 25 Participants | 56 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Exhaled Nitric Oxide cocentration (eNO) (ppb) | 35.0 parts per billion (p/b) | 43.0 parts per billion (p/b) | 40.5 parts per billion (p/b) |
| Forced Expiratory Volume in 1 sec (FEV1) (L) | 2.79 Liters (L) | 3.01 Liters (L) | 2.89 Liters (L) |
| Forced Vital Capacity (FVC) (L) | 3.78 Liters (L) | 4.11 Liters (L) | 4.04 Liters (L) |
| Peak Expiratory Flow Rate (PEFR) (L/s) | 6.90 Liters/second (L/s) | 7.66 Liters/second (L/s) | 7.27 Liters/second (L/s) |
| Percent of Asthma Control Test (ACT) score ≤ 19 | 18 Participants | 20 Participants | 38 Participants |
| Precent predicted Forced Expiratory Volume in 1 sec (FEV1) | 86.7 Percent | 84.1 Percent | 85.9 Percent |
| Precent predicted Forced Vital Capacity (FVC) | 102.2 Percent | 103.7 Percent | 103.0 Percent |
| Precent predicted Peak Expiratory Flow Rate (PEFR) | 92.2 Percent | 92.6 Percent | 92.2 Percent |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 5 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 5 Participants | 6 Participants | 11 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) White | 17 Participants | 21 Participants | 38 Participants |
| Reported use of Short Acting Beta Adrenergic Medication (SABA) > 3/week | 3 Participants | 7 Participants | 10 Participants |
| Sex: Female, Male Female | 23 Participants | 23 Participants | 46 Participants |
| Sex: Female, Male Male | 12 Participants | 10 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 35 | 0 / 33 |
| other Total, other adverse events | 0 / 35 | 0 / 33 |
| serious Total, serious adverse events | 0 / 35 | 0 / 33 |
Outcome results
Primary
Magnitude Change of Airway Reactivity Measured by Methacholine PC20FEV1
Change in PEC20FEV1 measured after biofeedback from the PC20FEV1 measured at baseline
Time frame: 4-weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| HRV-BF | Magnitude Change of Airway Reactivity Measured by Methacholine PC20FEV1 | 2.9782 mg/ml |
| PBO-BF | Magnitude Change of Airway Reactivity Measured by Methacholine PC20FEV1 | 2.1181 mg/ml |
p-value: >0.1GEE regression