Clinical trial NCT04025528: Pathophysiology of Hypoventilation in Obesity and Effects of Bariatric Intervention
Official title: Pathophysiology of Hypoventilation in Obesity and Effects of Bariatric Intervention: PHOEBI Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Obesity Hypoventilation Syndrome (OHS)
Lead sponsor: Guy's and St Thomas' NHS Foundation Trust
Sponsor class: OTHER
First posted: 2019-07-19
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Obese patients who are considering bariatric surgery intervention

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Expiratory flow limitation as measured by forced oscillation testing
timeFrame: 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
measure: Degree of change in expiratory flow limitation
timeFrame: 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 outcomes:
measure: Closing capacity
timeFrame: 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
measure: Degree of change in closing capacity
timeFrame: 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
measure: Correlation between closing capacity and expiratory flow limitation
timeFrame: 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
measure: Intra-abdominal pressure
timeFrame: 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
measure: Correlation between intra-abdominal pressure, closing capacity and expriatory flow limitation
timeFrame: 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
measure: Upper airway collapsibility
timeFrame: 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
measure: Lung compliance
timeFrame: 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
measure: Respiratory muscle strength (maximal inspiratory pressure/maximal expiratory)
timeFrame: 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
measure: Respiratory muscle strength (SNIP test)
timeFrame: 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
measure: Daytime neural respiratory drive (para-sternal electromyography measurements)
timeFrame: 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
measure: Daytime neural respiratory drive (diaphragm electromyography measurements)
timeFrame: 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
measure: Nocturnal neural respiratory drive (para-sternal electromyography measurements)
timeFrame: 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
measure: Nocturnal neural respiratory drive (diaphragm electromyography measurements)
timeFrame: 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
measure: Quality of life post bariatric surgery with SF-36
timeFrame: 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
measure: Quality of life post bariatric surgery with EQ-5D
timeFrame: 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
measure: Symptom change after commencement of medical therapy compared to bariatric surgery measured with Epworth Sleepiness Scale
timeFrame: 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
measure: Symptom change after commencement of medical therapy compared to bariatric surgery measured with mMRC (modified medical research council) dypnoea score
timeFrame: 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
measure: Symptom change after commencement of medical therapy compared to bariatric surgery measured with Multi-dimensional dyspnoea profile
timeFrame: 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
measure: Symptom change after commencement of medical therapy compared to bariatric surgery measured with Severe Respiratory Insufficiency Questionnaire
timeFrame: 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
measure: Changes in healthcare resource usage in OHS patients post bariatric surgery
timeFrame: 6 months pre bariatric surgery and 6 months post bariatric surgery
measure: Improvement in daytime CO2 levels
timeFrame: 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
measure: Improvement in apnoea-hyponoea index
timeFrame: Before bariatric surgery on enrolment and 6 months after bariatric surgery
measure: Improvement in mean nocturnal oxygen saturation during sleep
timeFrame: Before bariatric surgery on enrolment and 6 months after bariatric surgery
measure: Improvement in mean time spent below 90% oxygen saturation during sleep
timeFrame: Before bariatric surgery on enrolment and 6 months after bariatric surgery
measure: Changes in sleep architecture measured by %slow wave sleep and %REM sleep
timeFrame: Before bariatric surgery on enrolment and 6 months after bariatric surgery
measure: Improvement in diaphragm function
timeFrame: 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
measure: Improvement in glycaemic control
timeFrame: 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 outcomes:
measure: Spectrum of sleep disordered breathing
timeFrame: 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
measure: Choice of bariatric surgery
timeFrame: 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
Locations:
city: London
country: United Kingdom
facility: Guy's and St Thomas' NHS Trust
Study officials:
affiliation: Guy's and St Thomas NHS Trust
name: Joerg Steier, PhD
role: PRINCIPAL_INVESTIGATOR
References: