Ketogenic Diet for Obesity Hypoventilation Syndrome (KETOHS)

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.

Study Overview

• Status: Completed
• Conditions: Hypercapnic Respiratory Failure; Obesity Hypoventilation Syndrome; Ketogenic Dieting
• Intervention / Treatment: Dietary supplement: Ketogenic Diet

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins Bayview Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2019
• Primary Completion (Actual): June 28, 2022
• Study Completion (Actual): June 28, 2022

Study Registration Dates

• First Submitted: September 26, 2019
• First Submitted That Met QC Criteria: September 26, 2019
• First Posted (Actual): September 30, 2019

Study Record Updates

• Last Update Posted (Actual): July 1, 2022
• Last Update Submitted That Met QC Criteria: June 28, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Respiratory Tract Diseases; Apnea; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Disease; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Signs and Symptoms, Respiratory; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Syndrome; Obesity; Respiratory Insufficiency; Hypoventilation; Obesity Hypoventilation Syndrome
• Other Study ID Numbers: IRB00212924

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No