Ketogenic Diet for Obesity Hypoventilation Syndrome

Study Overview
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Brief Summary
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Obesity hypoventilation syndrome (OHS) is a condition that occurs in small percentage of obese people that causes high carbon dioxide and low oxygen levels in the blood. OHS is associated with respiratory failure, pulmonary hypertension, and death. The cause of OHS is unclear. Since not all obese people develop OHS, it is believed that hormone imbalances can contribute to the breathing problem. Some diets can change the body's hormones. For example, low-carbohydrate, high fat ketogenic diets (KD) may decrease insulin and glucose levels and increase sensitivity to other hormones. The investigators hypothesize that a KD will improve breathing in OHS patients, even in the absence of weight loss.

Detailed Description
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Obesity hypoventilation syndrome (OHS) is a condition that occurs in small percentage of obese people, that leads to high carbon dioxide levels and low oxygen levels in the blood. OHS is associated with respiratory failure, pulmonary hypertension, hospital admissions, and death. Unfortunately, there is no treatment for OHS besides massive weight loss which often requires bariatric surgery. In this study, the investigators are examining whether switching from a regular diet to a ketogenic diet will improve breathing, oxygen, and carbon dioxide levels in OHS patients. After a few days-weeks on KD, hormone changes are known to occur and the investigators are examining whether these hormonal changes could stimulate breathing. This is a pilot study to examine the effects of a 12 day KD on OHS. The outcomes of the study include blood oxygen, carbon dioxide levels, plasma levels of hormones such as insulin, leptin, sleep studies, body composition a, weight, and metabolic rate.

Official Title
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Ketogenic Diet for Obesity Hypoventilation Syndrome

Conditions
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Obesity Hypoventilation Syndrome, Ketogenic Dieting, Hypercapnic Respiratory Failure

Intervention / Treatment
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* Dietary Supplement: Ketogenic Diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Obesity (BMI≥30 kg/m2) Hypercapnia (PaCO2>45 or PvCO2>50) on blood gas, OR a sleep study with end-tidal/transcutaneous CO2 monitoring showing an awake CO2 level >50 Participants without blood gas data may also have suspected OHS on the basis of serum bicarbonate >=28 mEq/L Lack of an alternative pulmonary diagnosis that adequately explains hypercapnia. Note that a documented pulmonary diagnosis (e.g. chronic obstructive pulmonary disease (COPD) or asthma) per se will not necessarily exclude subjects, since OHS is often misdiagnosed as obstructive lung disease. Functional or radiographic data must corroborate the presence of the alternate diagnosis. Subjects must have had a sleep study and clinical evaluation for sleep apnea. Most subjects with OHS are expected to have concomitant obstructive sleep apnea (OSA). This information is necessary to determine whether continuous positive airway pressure (CPAP)/noninvasive ventilation (NIV) will be used on the research sleep studies. Exclusion Criteria: Concomitant participation in another weight loss or diet program Patients with diabetes taking Sodium-glucose Cotransporter-2 (SGLT2) inhibitors (due to risk of diabetic ketoacidosis) Patients with type 1 diabetes Any patients with a history of diabetic ketoacidosis Patients with incomplete sleep apnea diagnosis or management (i.e. those still acclimating to CPAP, or pending therapeutic decisions about OSA management) Known or suspected abuse of narcotics or alcohol Liver cirrhosis Uncontrolled gout History of chronic renal insufficiency requiring dialysis Females who are pregnant, breast-feeding, or intending to become pregnant Food allergies or diet restrictions that research nutritionists cannot accommodate FOLLOW THIS LINK TO SEE IF YOU QUALIFY: https://mrprcbcw.hosts.jhmi.edu/redcap/surveys/?s=RYX7DELK9Y

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketogenic Diet<br>Participants will receive the ketogenic diet. | Dietary Supplement: Ketogenic Diet<br>* Subjects will undergo ketogenic diet at a 2.5:1 (fat: carb + protein) ratio for a 2-week period.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Awake venous carbon dioxide (PvCO2) Level | Measured in mmHg. | Baseline (pre keto diet) and 2 weeks post keto diet | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Venous pH | Measured in moles per liter. | Once per week, over 4 weeks | 
| Change in Glucose level | Measured in g/dL. | Once per week, over 4 weeks | 
| Change in Insulin level | Measured in mIU/L. | Once per week, over 4 weeks | 
| Change in leptin level | Measured in ng/mL. | Once per week, over 4 weeks | 
| Change in beta-Hydroxybutyrate level | Measured in mg/dL. | Once per week, over 4 weeks | 
| Glucose profile | Using continuous glucose monitoring (CGM), to measured glucose level (g/dL) each day at home. | Continuously measured over 4 weeks | 
| Change in Body weight (kg) |  | Once per week, over 4 weeks | 
| Change in Oxygen saturation | Measured as a percentage. | Once per week, over 4 weeks | 
| Change in Blood Pressure | Measured in mmHg. | Once per week, over 4 weeks | 
| Change in percentage of body fat | The investigators will measure percentage body fat using the Bioelectrical impedance analysis (BIA). | Once every 2 weeks, over 4 weeks | 
| Change in Apnea Hypopnea Index | The apnea hypopnea index (AHI) is derived from combined information from EEG signals, flow sensors, respiratory belts, and carbon dioxide censors and is a measure of severity of sleep apnea. AHI < 5 is considered normal. AHI 5-15 is considered mild sleep apnea. AHI 15-30 is considered moderate sleep apnea. AHI >30 is considered severe sleep apnea. | Once every 2 weeks, over 4 weeks | 
| Change in LDL Cholesterol | Measured in mg/dL. | Once per week, over 4 weeks | 
| Change in HDL Cholesterol | Measured in mg/dL. | Once per week, over 4 weeks | 
| Change in Triglyceride level | Measured in mg/dL. | Once per week, over 4 weeks |