Mechanical Unloading for Obesity in Aging

Overseen By Abide Abulimiti, Ph.D.

Age: 65+

Sex: Any

Trial Phase: Academic

Sponsor: University of Texas Southwestern Medical Center

Must not be taking: Exercise capacity drugs

Disqualifiers: Smoking, Heart disease, Hypertension, Asthma, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

72 Participants Needed

Trial Summary

What is the purpose of this trial?

The overall objective of this application is to investigate the effects of obesity on lung function, exercise tolerance, and DOE in older obese adults as compared with older adults without obesity, using a novel probe for mechanically unloading the thorax at rest and during exercise. The investigators will use 1) continuous negative cuirass pressure, and 2) assisted biphasic cuirass ventilation to decrease obesity-related effects in older obese adults. Our approach will be to examine respiratory function, exercise tolerance, and DOE with and without mechanical unloading in older obese men and women (65-75 yr), including those with respiratory symptoms (defined by a score of 1 or 2 on the modified Medical Research Council Dyspnea Scale), as compared with older adults without obesity. Specific Aims: The investigators will test the following hypotheses in older adults with and without obesity: Aim 1) Obesity will decrease respiratory function but to a greater extent in older obese adults with respiratory symptoms, (as evidenced by altered pulmonary function and breathing mechanics at rest); Aim 2) Obesity will decrease exercise tolerance (as evidenced by peak V•O2 in ml/min/kg, i.e., physical fitness), but not cardiorespiratory fitness (as evidenced by peak V•O2 in % of predicted based on ideal body wt), except in older obese adults with respiratory symptoms where both may be reduced during graded cycle ergometry. Aim 3) Obesity will increase DOE but to a greater extent in older obese adults with respiratory symptoms as evidenced by increased ratings of perceived breathlessness (sensory \& affective dimensions) during exercise. Aim 4) Mechanical unloading of the thorax will improve respiratory function, submaximal exercise tolerance, and DOE in older obese adults, but to a greater extent in older obese adults with respiratory symptoms.

Do I have to stop taking my current medications for the trial?

The trial requires that you do not take any current medications that may interfere with exercise capacity. If you are on such medications, you may need to stop them to participate.

What data supports the idea that Mechanical Unloading for Obesity in Aging is an effective treatment?

The available research shows that mechanical ventilation strategies, which are similar to Mechanical Unloading for Obesity in Aging, can improve lung function in obese patients. For example, using specific ventilatory settings helps improve lung volumes and gas exchange, which are crucial for better breathing. Additionally, non-invasive ventilation has been shown to improve respiratory parameters and survival rates in morbidly obese patients with breathing difficulties. These findings suggest that similar approaches, like Mechanical Unloading, could be effective in managing obesity-related respiratory issues. ^{1 2 3 4 5}

What safety data exists for mechanical unloading treatments for obesity in aging?

The provided research abstracts do not directly address the safety data for mechanical unloading treatments such as Mechanical Unloading of the Thorax, Continuous Negative Cuirass Pressure, or Assisted Biphasic Cuirass Ventilation. Instead, they focus on the effects of positive end-expiratory pressure and mechanical ventilation in obese patients, particularly in ICU settings. These studies explore respiratory mechanics, lung recruitment, and ventilator-induced lung injury in morbidly obese patients, but do not provide specific safety data for the treatments in question. ^{1 2 4 6 7}

Is the treatment 'Mechanical unloading of the Thorax' a promising treatment for obesity in aging?

Yes, mechanical unloading of the thorax, which helps with breathing by reducing the effort needed to breathe, shows promise as a treatment. It can improve breathing efficiency and reduce the strain on the chest, potentially benefiting people with obesity. ^{1 2 8 9 10}

Research Team

Tony G Babb, Ph.D.

Principal Investigator

UT Southwestern Medical Center

Eligibility Criteria

This trial is for healthy older adults aged 65-75 with normal lung function and specific body fat percentages (men: 30-50%, women: 35-55%). Participants should be nonsmokers, without significant mental illness, uncontrolled hypertension, serious health conditions affecting exercise capacity, metabolic disorders like diabetes, or a history of substance abuse. Only postmenopausal women are eligible.

Inclusion Criteria

Nonsmokers with no history of smoking

I can exercise without being limited by a physical condition.

I am a postmenopausal woman.

Exclusion Criteria

Individuals participating in regular vigorous conditioning exercise more than two times per week

Subjects with an exceedingly high exercise capacity (greater than 2 SD of predicted)

I am a woman who has not gone through menopause.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Initial assessment of lung function, exercise tolerance, and DOE using various measurements and questionnaires

1 week

1 visit (in-person)

Intervention

Participants undergo mechanical unloading of the thorax using continuous negative cuirass pressure and assisted biphasic cuirass ventilation

6 weeks

4 visits (in-person)

Follow-up

Participants are monitored for changes in respiratory function, exercise tolerance, and DOE after intervention

4 weeks

2 visits (in-person)

Treatment Details

Interventions

• Mechanical unloading of the Thorax

Trial Overview The study tests if mechanical unloading of the thorax using an external cuirass can improve lung function and exercise tolerance in obese older adults. It compares respiratory functions and breathlessness during rest and exercise between those with obesity-related respiratory symptoms and those without.

Participant Groups

Group I: Interventional Arm Experimental Treatment 1 Intervention

Older group of adults (65-75 yrs). Everyone enrolled uses the 'intervention'/ external cuirass - mechanical unloading of thorax

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Findings from Research

In a study of 14 critically ill morbidly obese patients, using recruitment maneuvers followed by titration of positive end-expiratory pressure (PEEP) significantly improved lung volumes and oxygenation, indicating a more effective mechanical ventilation strategy.

The standard PEEP levels set by clinicians were found to be inadequate, leading to lower lung volumes and worse oxygenation, highlighting the need for tailored PEEP adjustments in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recruitment Maneuvers and Positive End-Expiratory Pressure Titration in Morbidly Obese ICU Patients. Pirrone, M., Fisher, D., Chipman, D., et al.[2022]

In a study involving 12 patients with class III obesity and 6 control participants, using CPAP (Continuous Positive Airway Pressure) matched to pleural pressure significantly decreased the work of breathing and improved respiratory mechanics without affecting heart function.

The CPAP treatment also led to better oxygen saturation and more even distribution of tidal volume in the lungs, indicating it can be a safe and effective intervention for improving breathing in patients with severe obesity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pleural Pressure Targeted Positive Airway Pressure Improves Cardiopulmonary Function in Spontaneously Breathing Patients With Obesity. Florio, G., De Santis Santiago, RR., Fumagalli, J., et al.[2022]

Obesity leads to specific challenges in mechanical ventilation due to decreased lung volume and increased airway inflammation, which can impair gas exchange and respiratory mechanics.

To minimize lung injury and manage ventilation effectively in obese patients, strategies such as stepwise recruitment maneuvers and careful tidal volume titration are essential to reduce lung stress and inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mechanical ventilation in obese patients. Leme Silva, P., Pelosi, P., Rocco, PR.[2022]

In critically ill obese patients on mechanical ventilation, adopting a sitting position significantly improved respiratory mechanics by relieving expiratory flow limitation and reducing auto-positive end-expiratory pressure, leading to lower alveolar pressures.

Applying positive end-expiratory pressure further enhanced these benefits, effectively reversing expiratory flow limitation without increasing plateau pressure, making it a beneficial strategy for managing respiratory function in severely obese patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of sitting position and applied positive end-expiratory pressure on respiratory mechanics of critically ill obese patients receiving mechanical ventilation*. Lemyze, M., Mallat, J., Duhamel, A., et al.[2022]

Morbid obesity significantly impairs respiratory function, leading to increased risks of both acute hypoxaemic and hypercapnic respiratory failure, making early diagnosis and management crucial.

Non-invasive ventilation has been shown to improve respiratory outcomes and survival in morbidly obese patients with hypoventilation, reducing the need for invasive mechanical ventilation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Managing acute respiratory decompensation in the morbidly obese. Bahammam, AS., Al-Jawder, SE.[2022]

In a study of 15 postoperative morbidly obese patients on mechanical ventilation, tidal expiratory flow limitation (EFL) was found in 10 patients, indicating that EFL is common in this population when no positive end-expiratory pressure (PEEP) is applied.

Applying an average PEEP of 7.5 cm H2O effectively abolished EFL and improved respiratory mechanics, although it did not significantly enhance gas exchange, which was likely impaired due to atelectasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expiratory flow limitation in morbidly obese postoperative mechanically ventilated patients. Koutsoukou, A., Koulouris, N., Bekos, B., et al.[2013]

In mechanically ventilated patients, the risk of ventilator-induced lung injury is influenced by both lung and chest wall mechanics, particularly in those with morbid obesity and severe hypoxemia, as shown by a study involving 213 subjects across four groups.

The study found that driving pressure and dynamic power were significantly higher in patients with morbid obesity and severe hypoxemia, indicating that ventilator settings should be adjusted to account for these factors to minimize lung injury risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elastic Power of Mechanical Ventilation in Morbid Obesity and Severe Hypoxemia. Syed, MKH., Selickman, J., Evans, MD., et al.[2023]

In a study involving five piglets and five adult rabbits with lung injuries, respiratory mechanical unloading significantly reduced chest wall distortion (CWD), improving breathing mechanics and efficiency.

The technique led to increased tidal volume and decreased partial pressure of arterial CO2, suggesting enhanced ventilatory efficiency without affecting the respiratory rate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of respiratory mechanical unloading on thoracoabdominal motion in meconium-injured piglets and rabbits. Schulze, A., Suguihara, C., Gerhardt, T., et al.[2019]

The study on eight anesthetized cats demonstrated that elastic unloading (negative ventilator compliance) can effectively adjust the total compliance of the lung-respirator system, with measured values closely aligning with theoretical predictions.

Elastic unloading improved tidal volume and reduced arterial PCO2 in healthy lungs, suggesting its potential benefits in mechanical ventilation, especially during the weaning process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assisted mechanical ventilation using elastic unloading: a study in cats with normal and injured lungs. Schulze, A., Schaller, P., Jonzon, A., et al.[2008]

Recruitment maneuvers followed by positive end-expiratory pressure (PEEP) are effective in improving ventilation for obese patients undergoing bariatric surgery, as shown in a systematic review of 13 randomized controlled trials.

Noninvasive positive pressure ventilation (NIPPV) during induction is beneficial for preventing atelectasis and extending safe apnea duration, highlighting its importance in managing ventilation challenges in obese patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effective Ventilation Strategies for Obese Patients Undergoing Bariatric Surgery: A Literature Review. Hu, XY.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Recruitment Maneuvers and Positive End-Expiratory Pressure Titration in Morbidly Obese ICU Patients. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Pleural Pressure Targeted Positive Airway Pressure Improves Cardiopulmonary Function in Spontaneously Breathing Patients With Obesity. [2022]

3. Italy pubmed.ncbi.nlm.nih.gov

Mechanical ventilation in obese patients. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Effects of sitting position and applied positive end-expiratory pressure on respiratory mechanics of critically ill obese patients receiving mechanical ventilation*. [2022]

5. Australia pubmed.ncbi.nlm.nih.gov

Managing acute respiratory decompensation in the morbidly obese. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Expiratory flow limitation in morbidly obese postoperative mechanically ventilated patients. [2013]

7. United States pubmed.ncbi.nlm.nih.gov

Elastic Power of Mechanical Ventilation in Morbid Obesity and Severe Hypoxemia. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Effects of respiratory mechanical unloading on thoracoabdominal motion in meconium-injured piglets and rabbits. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Assisted mechanical ventilation using elastic unloading: a study in cats with normal and injured lungs. [2008]

10. United States pubmed.ncbi.nlm.nih.gov

Effective Ventilation Strategies for Obese Patients Undergoing Bariatric Surgery: A Literature Review. [2022]