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Pathophysiology of Hypoventilation in Obesity and Effects of Bariatric Intervention

Recruiting
Conditions
Obesity Hypoventilation Syndrome (OHS)
Interventions
Procedure: Bariatric Surgery
Registration Number
NCT04025528
Lead Sponsor
Guy's and St Thomas' NHS Foundation Trust
Brief 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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
30
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 & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
EucapnicBariatric SurgeryObese patients with normal daytime carbon dioxide levels
HypercapnicBariatric SurgeryObese patients with daytime hypercapnia
Primary Outcome Measures
NameTimeMethod
Degree of change in expiratory flow limitationMeasurements 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

Explore whether the degree of positional change in expiratory flow limitation can differentiate between eucapnic and hypercapnic patients

Expiratory flow limitation as measured by forced oscillation testingMeasurements 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

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

Secondary Outcome Measures
NameTimeMethod
Intra-abdominal pressureMeasurements 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

We will measure intra-abdominal pressure and explore whether hypercapnic patients have increased intra-abdominal pressure. Positional changes will be measured

Daytime neural respiratory drive (para-sternal electromyography measurements)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 as measured by parasternal electromyography (EMG) measurements can differentiate between hypercapnic and eucapnic patients

Daytime neural respiratory drive (diaphragm electromyography measurements)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 as measured by diaphragm electromyography (EMG) measurements can differentiate between hypercapnic and eucapnic patients

Upper airway collapsibilityMeasurements 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

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

Lung complianceMeasurements 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

Measurement of lung compliance with pressure volume curve including measurements in different positions (upright, 45 degrees and supine)

Improvement in apnoea-hyponoea indexBefore bariatric surgery on enrolment and 6 months after bariatric surgery

Patients will have diagnostic sleep study before and after bariatric surgery

Closing capacityMeasurements 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

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

Correlation between closing capacity and expiratory flow limitationMeasurements 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

Compare outcome 1 and 3 to explore whether there is a relationship between expiratory flow limitation and closing capacity

Correlation between intra-abdominal pressure, closing capacity and expriatory flow limitationMeasurements 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

Compare outcome 1,3 and 6. This is a complex multi-compartment model that can differentiate hypercapnia and eucapnic patients

Quality of life post bariatric surgery with EQ-5DMeasurements 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 changes after bariatric surgery more than with standard medical therapy

Improvement in mean time spent below 90% oxygen saturation during sleepBefore bariatric surgery on enrolment and 6 months after bariatric surgery

Patients will have diagnostic sleep study before and after bariatric surgery

Nocturnal neural respiratory drive (diaphragm electromyography measurements)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 as measured by diaphragm electromyography (EMG) measurements can differentiate between hypercapnic and eucapnic patients

Symptom change after commencement of medical therapy compared to bariatric surgery measured with Severe Respiratory Insufficiency QuestionnaireMeasurements 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 bariatric surgery is more than with standard medical therapy

Changes in sleep architecture measured by %slow wave sleep and %REM sleepBefore bariatric surgery on enrolment and 6 months after bariatric surgery

Patients will have diagnostic sleep study before and after bariatric surgery

Degree of change in closing capacityMeasurements 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

Explore whether the degree of positional change in closing capacity can differentiate between eucapnic and hypercapnic patients

Nocturnal neural respiratory drive (para-sternal electromyography measurements)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 as measured by parasternal electromyography (EMG) measurements can differentiate between hypercapnic and eucapnic patients

Quality of life post bariatric surgery with SF-36Measurements 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 changes after bariatric surgery more than with standard medical therapy

Symptom change after commencement of medical therapy compared to bariatric surgery measured with Multi-dimensional dyspnoea profileMeasurements 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 bariatric surgery is more than with standard medical therapy

Respiratory muscle strength (maximal inspiratory pressure/maximal expiratory)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

Measurement of inspiratory and expiratory muscle strength

Respiratory muscle strength (SNIP test)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

Measurement of sniff nasal inspiratory pressure

Symptom change after commencement of medical therapy compared to bariatric surgery measured with Epworth Sleepiness ScaleMeasurements 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 bariatric surgery is more than with standard medical therapy

Symptom change after commencement of medical therapy compared to bariatric surgery measured with mMRC (modified medical research council) dypnoea scoreMeasurements 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 bariatric surgery is more than with standard medical therapy

Changes in healthcare resource usage in OHS patients post bariatric surgery6 months pre bariatric surgery and 6 months 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

Improvement in mean nocturnal oxygen saturation during sleepBefore bariatric surgery on enrolment and 6 months after bariatric surgery

Patients will have diagnostic sleep study before and after bariatric surgery

Improvement in daytime CO2 levelsMeasurements 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

Arterial blood gas performed before and after bariatric surgery with improvement in CO2 levels

Improvement in diaphragm functionMeasurements 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

Diaphragm thickening will be measured by ultrasound assessment

Improvement in glycaemic controlMeasurements 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

HbA1C will be measured before and after bariatric surgery

Trial Locations

Locations (1)

Guy's and St Thomas' NHS Trust

🇬🇧

London, United Kingdom

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