Pathophysiology of Hypoventilation in Obesity and Effects of Bariatric Intervention (PHOEBI)

Pathophysiology of Hypoventilation in Obesity and Effects of Bariatric Intervention: PHOEBI Study

Breathing is impacted by obesity. Early changes are characterised by significant breathing abnormalities during sleep (a condition called sleep disordered breathing, the most common of which is obstructive sleep apnoea). As the breathing changes worsen in severity, it may result in a rise in carbon dioxide levels during daytime causing a condition called obesity hypoventilation syndrome (OHS). The current treatment for obesity related breathing changes include supportive breathing therapy at night, optimisation of associated medical conditions and weight loss.

Weight management is an important part of obesity treatment. Weight loss strategies such as life-style modification do not always work. Weight loss surgery (bariatric surgery) has been shown to be an effective weight management intervention with long-term results. This study aims to understand breathing changes that occurs due to obesity and their resolution after weight loss surgery. The investigators are aiming to recruit participants with sleep disordered breathing who are currently awaiting bariatric surgery. In particular, the investigators are interested in comparing breathing changes in participants with OHS, who have abnormal regulation of their carbon dioxide levels, and participants with sleep disordered breathing with normal CO2 regulation.

Participants will be recruited through outpatient clinics for sleep disordered breathing. The participants will undergo comprehensive breathing assessments on enrolment including an overnight sleep study. Participants will undergo further daytime breathing assessments before and after their bariatric surgery. End of study will be 6 months after surgery - participants will have a final comprehensive breathing assessment including an overnight sleep study to review resolution of their breathing changes. Depending on the wait list time for the bariatric surgery, it is anticipated that participants will be enrolled in the study for 2 years.

Study Overview

• Status: Recruiting
• Conditions: Obesity Hypoventilation Syndrome (OHS)
• Intervention / Treatment: Procedure: Bariatric Surgery

• Study Type: Observational
• Enrollment (Anticipated): 30

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SE17EH
    • Recruiting
    • Guy's and St Thomas' NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Obese patients who are considering bariatric surgery intervention

Description

Inclusion Criteria:

1. Patients 18 years or older
2. BMI > 40
3. Patients with significant sleep disordered breathing requiring treatment
4. Patient is being assessed for bariatric surgery for either gastric sleeve or gastric bypass surgery

Exclusion Criteria:

1. Patients with decompensated hypercapnic respiratory failure (pH< 7.3)
2. Chronic hypercapnic respiratory failure due to a cause other than obesity such as neuromuscular, chest wall or airway disease
3. Unstable cardiac disease including coronary artery disease and heart failure
4. Significant co-morbid psychiatric disease requiring anti-psychotic medications
5. Chronic pain syndrome on high dose opioid medications
6. Treatment for drug or alcohol addiction
7. Cognitive impairment that would prevent informed consent
8. Pregnancy
9. Need for long-term renal replacement therapy
10. Patients who undergo bariatric intervention with gastric balloon or gastric band.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Hypercapnic; Obese patients with daytime hypercapnia	Procedure: Bariatric Surgery; Weight loss surgery with either gastric sleeve or gastric bypass surgery
Eucapnic; Obese patients with normal daytime carbon dioxide levels	Procedure: Bariatric Surgery; Weight loss surgery with either gastric sleeve or gastric bypass surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Expiratory flow limitation as measured by forced oscillation testing	Measurement of expiratory flow limitation at different position including upright, 45 degrees and supine. We will explore whether expiratory flow limitation can differentiate hypercapnic and eucapnic patients	Measurements on enrolment into study; measurements prior to bariatric surgery (once patients has a surgery date); measurements 2-4 weeks after bariatric surgery; and end of study measurements 6 months after bariatric surgery
Degree of change in expiratory flow limitation	Explore whether the degree of positional change in expiratory flow limitation can differentiate between eucapnic and hypercapnic patients	Measurements on enrolment into study; measurements prior to bariatric surgery (once patient has a surgery date); measurements 2-4 weeks after bariatric surgery; and end of study measurements 6 months after bariatric surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Closing capacity	Measurement of closing capacity at different position including upright, 45 degrees and supine. We will explore whether expiratory flow limitation can differentiate hypercapnic and eucapnic patients	Measurements on enrolment into study; measurements prior to bariatric surgery (once patient has a surgery date); measurements 2-4 weeks after bariatric surgery; and end of study measurements 6 months after bariatric surgery
Degree of change in closing capacity	Explore whether the degree of positional change in closing capacity can differentiate between eucapnic and hypercapnic patients	Measurements on enrolment into study; measurements prior to bariatric surgery (once patient has a surgery date); measurements 2-4 weeks after bariatric surgery; and end of study measurements 6 months after bariatric surgery
Correlation between closing capacity and expiratory flow limitation	Compare outcome 1 and 3 to explore whether there is a relationship between expiratory flow limitation and closing capacity	Measurements on enrolment into study; measurements prior to bariatric surgery (once patient has a surgery date); measurements 2-4 weeks after bariatric surgery; and end of study measurements 6 months after bariatric surgery
Intra-abdominal pressure	We will measure intra-abdominal pressure and explore whether hypercapnic patients have increased intra-abdominal pressure. Positional changes will be measured	Measurements on enrolment into study; measurements prior to bariatric surgery (once patient has a surgery date); measurements 2-4 weeks after bariatric surgery; and end of study measurements 6 months after bariatric surgery
Correlation between intra-abdominal pressure, closing capacity and expriatory flow limitation	Compare outcome 1,3 and 6. This is a complex multi-compartment model that can differentiate hypercapnia and eucapnic patients	Measurements on enrolment into study; measurements prior to bariatric surgery (once patient has a surgery date); measurements 2-4 weeks after bariatric surgery; and end of study measurements 6 months after bariatric surgery
Upper airway collapsibility	Measurement of upper airway collapsibility as measure by negative expiratory pressure. Explore whether there is a relationship between hypercapnic and eucapnic patients depending on degree of upper airway collapsibility	Measurements on enrolment into study; measurements prior to bariatric surgery (once patient has a surgery date); measurements 2-4 weeks after bariatric surgery; and end of study measurements 6 months after bariatric surgery
Lung compliance	Measurement of lung compliance with pressure volume curve including measurements in different positions (upright, 45 degrees and supine)	Measurements on enrolment into study; measurements prior to bariatric surgery (once patient has a surgery date); measurements 2-4 weeks after bariatric surgery; and end of study measurements 6 months after bariatric surgery
Respiratory muscle strength (maximal inspiratory pressure/maximal expiratory)	Measurement of inspiratory and expiratory muscle strength	Measurements on enrolment into study; measurements prior to bariatric surgery (once patient has a surgery date); measurements 2-4 weeks after bariatric surgery; and end of study measurements 6 months after bariatric surgery
Respiratory muscle strength (SNIP test)	Measurement of sniff nasal inspiratory pressure	Measurements on enrolment into study; measurements prior to bariatric surgery (once patient has a surgery date); measurements 2-4 weeks after bariatric surgery; and end of study measurements 6 months after bariatric surgery
Daytime neural respiratory drive (para-sternal electromyography measurements)	Daytime neural respiratory drive as measured by parasternal electromyography (EMG) measurements can differentiate between hypercapnic and eucapnic patients	Measurements on enrolment into study; measurements prior to bariatric surgery (once patient has a surgery date); measurements 2-4 weeks after bariatric surgery; and end of study measurements 6 months after bariatric surgery
Daytime neural respiratory drive (diaphragm electromyography measurements)	Daytime neural respiratory drive as measured by diaphragm electromyography (EMG) measurements can differentiate between hypercapnic and eucapnic patients	Measurements on enrolment into study; measurements prior to bariatric surgery (once patient has a surgery date); measurements 2-4 weeks after bariatric surgery; and end of study measurements 6 months after bariatric surgery
Nocturnal neural respiratory drive (para-sternal electromyography measurements)	Nocturnal neural respiratory drive as measured by parasternal electromyography (EMG) measurements can differentiate between hypercapnic and eucapnic patients	Measurements on enrolment into study; measurements prior to bariatric surgery (once patient has a surgery date); measurements 2-4 weeks after bariatric surgery; and end of study measurements 6 months after bariatric surgery
Nocturnal neural respiratory drive (diaphragm electromyography measurements)	Nocturnal neural respiratory drive as measured by diaphragm electromyography (EMG) measurements can differentiate between hypercapnic and eucapnic patients	Measurements on enrolment into study; measurements prior to bariatric surgery (once patient has a surgery date); measurements 2-4 weeks after bariatric surgery; and end of study measurements 6 months after bariatric surgery
Quality of life post bariatric surgery with SF-36	Quality of life changes after bariatric surgery more than with standard medical therapy	Measurements on enrolment into study; measurements prior to bariatric surgery (once patient has a surgery date); measurements 2-4 weeks after bariatric surgery; and end of study measurements 6 months after bariatric surgery
Quality of life post bariatric surgery with EQ-5D	Quality of life changes after bariatric surgery more than with standard medical therapy	Measurements on enrolment into study; measurements prior to bariatric surgery (once patient has a surgery date); measurements 2-4 weeks after bariatric surgery; and end of study measurements 6 months after bariatric surgery
Symptom change after commencement of medical therapy compared to bariatric surgery measured with Epworth Sleepiness Scale	Symptom change after bariatric surgery is more than with standard medical therapy	Measurements on enrolment into study; measurements prior to bariatric surgery (once patient has a surgery date); measurements 2-4 weeks after bariatric surgery; and end of study measurements 6 months after bariatric surgery
Symptom change after commencement of medical therapy compared to bariatric surgery measured with mMRC (modified medical research council) dypnoea score	Symptom change after bariatric surgery is more than with standard medical therapy	Measurements on enrolment into study; measurements prior to bariatric surgery (once patient has a surgery date); measurements 2-4 weeks after bariatric surgery; and end of study measurements 6 months after bariatric surgery
Symptom change after commencement of medical therapy compared to bariatric surgery measured with Multi-dimensional dyspnoea profile	Symptom change after bariatric surgery is more than with standard medical therapy	Measurements on enrolment into study; measurements prior to bariatric surgery (once patient has a surgery date); measurements 2-4 weeks after bariatric surgery; and end of study measurements 6 months after bariatric surgery
Symptom change after commencement of medical therapy compared to bariatric surgery measured with Severe Respiratory Insufficiency Questionnaire	Symptom change after bariatric surgery is more than with standard medical therapy	Measurements on enrolment into study; measurements prior to bariatric surgery (once patient has a surgery date); measurements 2-4 weeks after bariatric surgery; and end of study measurements 6 months after bariatric surgery
Changes in healthcare resource usage in OHS patients post bariatric surgery	Estimation of healthcare usage cost in the 6 months prior to surgery and 6 months post surgery including medication costs and re-admissions to hospital	6 months pre bariatric surgery and 6 months post bariatric surgery
Improvement in daytime CO2 levels	Arterial blood gas performed before and after bariatric surgery with improvement in CO2 levels	Measurements on enrolment into study; measurements prior to bariatric surgery (once patient has a surgery date); measurements 2-4 weeks after bariatric surgery; and end of study measurements 6 months after bariatric surgery
Improvement in apnoea-hyponoea index	Patients will have diagnostic sleep study before and after bariatric surgery	Before bariatric surgery on enrolment and 6 months after bariatric surgery
Improvement in mean nocturnal oxygen saturation during sleep	Patients will have diagnostic sleep study before and after bariatric surgery	Before bariatric surgery on enrolment and 6 months after bariatric surgery
Improvement in mean time spent below 90% oxygen saturation during sleep	Patients will have diagnostic sleep study before and after bariatric surgery	Before bariatric surgery on enrolment and 6 months after bariatric surgery
Changes in sleep architecture measured by %slow wave sleep and %REM sleep	Patients will have diagnostic sleep study before and after bariatric surgery	Before bariatric surgery on enrolment and 6 months after bariatric surgery
Improvement in diaphragm function	Diaphragm thickening will be measured by ultrasound assessment	Measurements on enrolment into study; measurements prior to bariatric surgery (once patient has a surgery date); measurements 2-4 weeks after bariatric surgery; and end of study measurements 6 months after bariatric surgery
Improvement in glycaemic control	HbA1C will be measured before and after bariatric surgery	Measurements on enrolment into study; measurements prior to bariatric surgery (once patient has a surgery date); measurements 2-4 weeks after bariatric surgery; and end of study measurements 6 months after bariatric surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Spectrum of sleep disordered breathing	We will look at sub-group analyses for outcomes 1-29 based on degree of hypoventilation as defined by ERS/ESRS working group	Measurements on enrolment into study; measurements prior to bariatric surgery (once patient has a surgery date); measurements 2-4 weeks after bariatric surgery; and end of study measurements 6 months after bariatric surgery
Choice of bariatric surgery	We will investigate whether outcomes 1-29 is different depending on type of surgery the patient undergoes (gastric bypass compared to gastric sleeve)	Measurements on enrolment into study; measurements prior to bariatric surgery (once patient has a surgery date); measurements 2-4 weeks after bariatric surgery; and end of study measurements 6 months after bariatric surgery

Collaborators and Investigators

• Sponsor: Guy's and St Thomas' NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2019
• Primary Completion (Anticipated): July 1, 2024
• Study Completion (Anticipated): July 1, 2024

Study Registration Dates

• First Submitted: June 21, 2019
• First Submitted That Met QC Criteria: July 16, 2019
• First Posted (Actual): July 19, 2019

Study Record Updates

• Last Update Posted (Actual): March 23, 2023
• Last Update Submitted That Met QC Criteria: March 22, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Apnea; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Signs and Symptoms, Respiratory; Sleep Apnea Syndromes; Respiratory Insufficiency; Sleep Apnea, Obstructive; Obesity; Hypoventilation; Obesity Hypoventilation Syndrome
• Other Study ID Numbers: 258045

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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