Pathophysiology of Hypoventilation in Obesity and Effects of Bariatric Intervention

Obesity Hypoventilation Syndrome (OHS) Clinical Trial

— PHOEBI  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04025528
• Other study ID #: 258045
• Status: Recruiting
• Start date: June 20, 2019
• Est. completion date: July 2024

Study information

• Verified date: March 2023
• Source: Guy's and St Thomas' NHS Foundation Trust
• Contact: Michael Cheng, MBBS
• Phone: +44 02071888070
• Email: michael.cheng[@]gstt.nhs.uk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: July 2024
• Est. primary completion date: July 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hypoventilation
• Obesity
• Obesity Hypoventilation Syndrome
• Obesity Hypoventilation Syndrome (OHS)

Intervention

Procedure:
• Bariatric Surgery
Weight loss surgery with either gastric sleeve or gastric bypass surgery

Locations

Country	Name	City	State
United Kingdom	Guy's and St Thomas' NHS Trust	London

Sponsors (1)

Lead Sponsor	Collaborator
Guy's and St Thomas' NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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