The effect of autonomic modulation on symptoms in patients with reflux
Research type
Research Study
Full title
A randomized single blinded parallel study to investigate the physiological modulation of the autonomic nervous system on symptoms in patients with reflux hypersensitivity
IRAS ID
278533
Contact name
Qasim Aziz
Contact email
Sponsor organisation
Joint Research Management Office, Queen Mary University of London
Clinicaltrials.gov Identifier
Duration of Study in the UK
1 years, 0 months, 0 days
Research summary
Research Summary
Reflux hypersensitivity is the disease that causes chest pain, heartburn and regurgitation and can impair patients’ quality of life. Pain modulators are often used for the treatment of reflux hypersensitivity, but the effect is not enough and more effective therapy is needed.
Slow deep breathing is the validated method to modulate the autonomic nervous system. In our previous study, slow deep breathing could increase the threshold of oesophageal pain in healthy volunteers. Therefore, slow deep breathing has the potential to be an effective treatment for reflux hypersensitivity and further study is warranted in the patient group.
The aims of this study are (1) to evaluate the feasibility of slow deep breathing and (2) to investigate the effect of autonomic nerve modulation by slow deep breathing on symptoms in patients with reflux hypersensitivity.
This is a randomized single-blinded parallel study and we aim to recruit 40 participants. They are allocated to either slow deep breathing or sham breathing group. During 4 weeks of each breathing protocol, participants are asked to fill out the online questionnaires every week. We compare feasibility and changes in symptoms between the 2 groups.
Summary of ResultsReflux hypersensitivity (RH) is an oesophageal condition where the oesophagus is sensitive to physiological amounts of gastro-oesophageal reflux. Previous studies demonstrate that modulation of the vagus nerve with slow deep breathing (SDB) attenuates oesophageal pain hypersensitivity, yet this has never been tested in patients with RH. We aimed to evaluate the feasibility of SDB versus sham breathing in patients with RH.
We conducted a randomised, single-blinded parallel study from April 2020 to May 2022 across five London sites: Royal London Hospital, Guys & St Thomas’ Hospital, University College London Hospital, Princess Grace Hospital and St Georges Hospital. Symptomatic patients with normal oesophageal acid exposure time and a positive symptom reflux association at impedance and pH monitoring (MII-pH) were included. We randomised patients to either SDB or sham breathing (10 minutes twice daily at home) for four weeks. Reflux symptoms and vagal tone (heart rate variability (HRV)) were recorded at five time-points. We assessed psychometric symptom scores at baseline and four week follow-up. Our primary end-point was feasibility and our secondary end-points were change in symptoms and HRV over time, evaluated using linear mixed effects models.
247 patients were assessed for eligibility of whom 57.5% (n=142) were eligible for inclusion and 30 patients completed the study: 13 in the SDB arm and 17 in the sham arm. Our recruitment rate was 16.2% (Wilson 95% CI: 12.1 to 21.3). 65% and 85% completed the trial in the SDB and sham arms respectively (p=0.27) with 98.3% compliance for both arms. The subjective acceptability of our intervention was 50% in the SDB and 40% in the sham arm r (p=0.89). We did not demonstrate any improvement in reflux symptoms over time or between the arms. Anxiety scores reduced significantly more in the SDB arm compared to the sham arm (p=0.02). There was no significant change in HRV in either arm, within days or over time.
We demonstrate limited feasibility for the remote investigation of SDB versus sham breathing in patients with RH. This is due to 42.5% of RH cases reported on MII-pH not fulfilling existing diagnostic criteria. Our intervention did not significantly impact reflux symptoms or vagal tone but did reduce anxiety. Future studies should assess these factors in a controlled environment such that quality of compliance with the intervention can be closely monitored.
REC name
South East Scotland REC 02
REC reference
20/SS/0026
Date of REC Opinion
6 Apr 2020
REC opinion
Further Information Favourable Opinion