Heart Rate Variability Biofeedback: It's Role in Asthma Therapeutics (BioAce)

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.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Behavioral: Heart rate variability biofeedback; Behavioral: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Health
  • New Jersey
    • Piscataway, New Jersey, United States, 08854
      • Rutgers Robert Wood Johnson Medical School

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Heart Rate Variability Biofeedback; During the first training session, we will measure heart rate variability (HRV) amplitude while the patient breathes for two minutes at a frequency ranging between 4.5-6.5 breaths/min, providing a "pacing stimulus" for this purpose. In subsequent sessions, the individual will be given personal heart rate variability biofeedback (HRV-BF), and instructed to increase the amplitude of heart rate oscillations, using a cardiotachometer tracing and frequency peaks as biofeedback stimuli, while avoiding hyperventilation symptoms, by breathing more shallowly, although slowly, at whatever frequency produces maximum-amplitude HRV.	Behavioral: Heart 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).
PLACEBO_COMPARATOR: Placebo Biofeedback; A credible Placebo Biofeedback (PBO-BF) 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.	Behavioral: Placebo; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Magnitude Change of Airway Reactivity Measured by Methacholine PC20FEV1	Change in PEC20FEV1 measured after biofeedback from the PC20FEV1 measured at baseline	4-weeks

Collaborators and Investigators

• Sponsor: Fred Wamboldt, MD
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); National Institutes of Health (NIH); National Jewish Health; Rutgers University
• Investigators: Principal Investigator: Frederick S Wamboldt, MD, National Jewish Health; Principal Investigator: Paul Lehrer, PhD, Rutgers Robert Wood Johnson Medical School

Publications and helpful links

General Publications

• Lehrer PM, Irvin CG, Lu SE, Scardella A, Roehmheld-Hamm B, Aviles-Velez M, Graves J, Vaschillo EG, Vaschillo B, Hoyte F, Nelson H, Wamboldt FS. Heart Rate Variability Biofeedback Does Not Substitute for Asthma Steroid Controller Medication. Appl Psychophysiol Biofeedback. 2018 Mar;43(1):57-73. doi: 10.1007/s10484-017-9382-0.

Study record dates

Study Major Dates

• Study Start: December 1, 2009
• Primary Completion (ACTUAL): October 1, 2015
• Study Completion (ACTUAL): January 1, 2018

Study Registration Dates

• First Submitted: February 14, 2014
• First Submitted That Met QC Criteria: May 5, 2016
• First Posted (ESTIMATE): May 9, 2016

Study Record Updates

• Last Update Posted (ACTUAL): January 15, 2019
• Last Update Submitted That Met QC Criteria: January 2, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Asthma; Biofeedback; Inhaled corticosteroids; Heart rate variability biofeedback
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: R01HL089495-01A2 (NIH)