HEART Rate Variability Biofeedback in LOng COVID-19 (HEARTLOC) (HEARTLOC)

Long COVID is a common but highly debilitating illness which develops after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or COVID-19). It is thought to affect as many as 1 in 7 people following COVID-19 infection. It can produce a vast array of symptoms including fatigue, breathlessness, fast heart rate, blood pressure disturbance, temperature disturbance, and dry mouth. Many of these symptoms could be explained by the nervous system being predominantly in a stress or 'fight or flight' response, also known as dysautonomia. One way of assessing whether this is the case is by measuring heart rate variability (HRV). This is the time variation between heart beats and is a marker of how stressed the nervous system is or how strong is the 'fight or flight' response. Heart rate variability can be measured using devices which are worn round the wrist or attach to the chest. An increased variability in heart rate corresponds with a more relaxed nervous system and decreased variability with a more stressed nervous system. Monitoring HRV in real-time and implementing interventions such as a breathing regime to maximise HRV is known as HRV biofeedback. The body can be trained out of the fight or flight response and into the 'rest and digest' mode response of the nervous system in this way and potentially significantly improve symptoms. We propose that for people with Long COVID, a programme of structured breathing exercises over 4 weeks whilst tracking HRV can demonstrate an improvement in HRV and consequently improve Long COVID symptoms.

Study Overview

• Status: Recruiting
• Conditions: COVID-19
• Intervention / Treatment: Behavioral: Heart Rate Variability Biofeedback (HRV-B)

Detailed Description

Participants will be shown a paced breathing programme and instructed to implement this for 10 minutes twice daily for 4 weeks. During the 10 minute breathing exercises, the participant will need to wear the Polar H10 chest strap and can remove this when finished. The breathing will ideally be a breathing pattern of a 4 second nasal inhale, and 6 second nasal exhale using the 'resonance' programme in the 'biofeedback' section of EliteHRV app. Researchers will monitor the participant's comfort and ease during this breathing demonstration, if participants find this breathing rate too slow then it can be tailored to ensure a tolerable slow breathing rate with minimal impact on symptoms - most likely by reducing both inhale and exhale in 1 second increments until a more tolerable breathing rate and pattern is found. They will be advised to monitor the graph of HRV on EliteHRV which allows real-time assessment of HRV and to aim to breathe in and out deeply to raise the HRV graph reading as much as possible each time. Participant Information Sheet provides more clarification and instruction on this. They will be advised to perform the breathing programme lying down with minimal distractions on waking in the morning and just before bed in the evening, preferably in the same location each time. During this 4 week period researchers will make weekly contact by phone to check progress and help resolve any queries. The participant will also have contact details of the researchers in case of any technical issues with Polar H10 chest strap or app during the 4 week study period.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Manoj Sivan, MD; Phone Number: 01133922564; Email: m.sivan@leeds.ac.uk

Study Locations

• United Kingdom
  • Yorkshire
    • Leeds, Yorkshire, United Kingdom, LS12 5SG
      • Recruiting
      • Leeds Community Healthcare NHS Trust
      • Contact: Manoj Sivan, MD; Phone Number: 01133922564; Email: manoj.sivan@nhs.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age > 18 years
• Confirmed Long COVID based on a positive PCR or antibody test and Long COVID symptoms as per the NICE criteria for post-COVID syndrome
• Current Leeds COVID Rehabilitation service user
• Self-rating of 'moderate/severe' on the Leeds COVID Rehabilitation Service Long COVID participant reported outcome measure (known as C19-YRS)
• Abnormal NASA Lean Test (NLT)

Exclusion Criteria:

• Age < 18 years
• Unable to use the wearable or smartphone app technology
• Cognitive problems or mental health disorders causing inability to consent
• Cardiac arrhythmia (current or prior tachyarrhythmia or bradyarrhythmia)
• Existing significant cardiorespiratory disease which might be expected to affect studied symptoms of palpitations, presyncope, breathlessness and fatigue (asthma not included in this definition)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Prospective cohort; Participants will be shown a paced breathing programme and instructed to implement this for 10 minutes twice daily for 4 weeks. During the 10-minute breathing exercises, the participant will need to wear the Polar H10 chest strap and can remove this when finished. The breathing will ideally be a breathing pattern of a 4-second nasal inhale, and 6-second nasal exhale using the 'resonance' programme in the 'biofeedback' section of EliteHRV app. They will be advised to monitor the graph of HRV on EliteHRV which allows real-time assessment of HRV and to aim to breathe in and out deeply to raise the HRV graph reading as much as possible each time. They will be advised to perform the breathing programme lying down with minimal distractions on waking in the morning and just before bed in the evening, preferably in the same location each time.

Behavioral: Heart Rate Variability Biofeedback (HRV-B); Breathing technique twice every day (10 min each) to increase HRV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modified C19-YRS (COVID-19 Yorkshire Rehabilitation Scale)	The C19-YRSm will be completed by the patient every week for a total of 6 weeks. There will be a total of 7 C19-YRSm documents completed. The C19-YRSm consists of 17 items with each item rated on a 4-point numerical rating scale from 0 (no symptom) to 3 (life disturbing or affecting all aspects of daily life). The C19-YRSm is divided into four subscales (range of total score for each subscale): symptom severity score (0-30), functional disability score (0-15), other symptoms (0-25), and overall health (0-10). A higher score for the first 3 subscores represents higher severity. Conversely, a lower overall health score represents greater severity.	Up to 6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HRV (Heart Rate Variability) score	We will be collecting both medium and short term HRV data. Participants will wear a Fitbit for 6 weeks which will collect HRV data whilst sleeping each night, thus collecting 6 weeks of consecutive nocturnal HRV data. In addition they will wear a Polar H10 chest strap for 10 minutes twice daily whilst performing breathing exercises to collect frequent short-term HRV data. For both data sets an increase in HRV is expected as this denotes an improvement in heart rate variability. Fitbit measures HRV in milliseconds on a scale from 0 to 100 (or more if HRV exceeds 100ms) A higher score represents more variability and therefore improvement. The Elite HRV also provides a score of HRV on a scale from 0 to 100 with a higher score representing improvement. The score is derived from the root mean square of successive differences between heartbeats in milliseconds (rMSSD).	Up to 6 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
COMPASS 31(Composite Autonomic Symptom Score)	The COMPASS 31 will be completed by the participant at the initial visit and again 6 weeks later at the end of the study. Autonomic symptoms are scored for different domains including orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder and pupillomotor. Total scores for each domain are multiplied by a set weighting and then added together to provide a score out of 100 representing severity of autonomic symptoms. A higher score represents greater severity	Up to 6 weeks
EQ5D-5L(EuroQol Five Dimension Quality of Life)	The EQ5D-5L will be completed by the participant at the initial visit and again 6 weeks later at the end of the study. 4 domains are assessed on a scale of 1 to 5: mobility, self-care, usual activities, pain/discomfort and anxiety and depression. A greater score represents greater severity. In addition participants self-rate their overall health on a scale f 0 to 100. 100 represents best health possible and 0 represents worst health possible.	Up to 6 weeks
aAP(Adapted Autonomic Profile)	Participant will complete an aAP at initial visit and again 6 weeks later at the end of the study. This test has binary outcome: normal or abnormal. There is no score generated by the test. We will assess whether those deemed normal or abnormal at the beginning change as a result of the intervention.	Up to 6 weeks
World Health Organisation Disability Assessment Schedule (WHODAS)	This is validated generic measure of functioning and disability. The 36-item scale captures six domains of life (cognition, mobility, self-care, getting along, life activities and participation) with a summary score ranging from 0 (no disability) to 100 (full disability)	Up to 6 weeks

Collaborators and Investigators

• Sponsor: University of Leeds
• Collaborators: University of Manchester; Leeds Comunity Healthcare NHS Trust

Study record dates

Study Major Dates

• Study Start (Actual): January 24, 2022
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): March 31, 2024

Study Registration Dates

• First Submitted: January 30, 2022
• First Submitted That Met QC Criteria: February 6, 2022
• First Posted (Actual): February 8, 2022

Study Record Updates

• Last Update Posted (Actual): October 24, 2022
• Last Update Submitted That Met QC Criteria: October 20, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Autonomic Nervous System; Long Covid; Post-Covid Syndrome; Post-Covid Condition; Post-Acute Covid Syndrome
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: 304567

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Data will be made available on requesting the corresponding author
• IPD Sharing Time Frame: After completion of data collection from 30 participants
• IPD Sharing Access Criteria: Open Science Framework registration
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No