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Ketogenic Diet for Obesity Hypoventilation Syndrome (KETOHS)

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ClinicalTrials.gov Identifier: NCT04108819
Recruitment Status : Recruiting
First Posted : September 30, 2019
Last Update Posted : September 30, 2019
Sponsor:
Information provided by (Responsible Party):
Johns Hopkins University

Brief Summary:

Obesity hypoventilation syndrome (OHS) causes hypercapnia (PaCO2>45) in subjects with obesity in the absence of lung disease, and is associated with respiratory failure, pulmonary hypertension, ICU admission, and death. Obesity is necessary, but not sufficient to cause OHS. Neuro-hormonal dysfunction is believed to impair respiratory CO2 sensitivity. In particular, leptin may play a role in OHS pathogenesis. In OHS, leptin levels are greatly elevated and correlate positively with PaCO2 independent of obesity or fat mass which suggests a linkage between defective central satiety and respiratory signaling.

Leptin resistance may be induced by carbohydrate-rich diets while very low carbohydrate "ketogenic" diets (KD) may enhance leptin sensitivity. The investigators hypothesize that a KD will correct hypoventilation in OHS patients, even in the absence of weight loss.


Condition or disease Intervention/treatment Phase
Obesity Hypoventilation Syndrome Ketogenic Dieting Hypercapnic Respiratory Failure Dietary Supplement: Ketogenic Diet Not Applicable

Detailed Description:

Prolonged starvation ketosis increased ventilatory responses to inhaled CO2 in obese, mild OHS patients. The investigators anticipate that this phenomenon can be induced by high-fat, low carbohydrate KD instead of an extreme and protracted fast; correct hypoventilation rapidly, since "ketosis" and leptin responses occur within 1 week of a KD; and be feasibly administered to patients with severe OHS, normalizing patients' gas exchange during wakefulness and while asleep.

This is a pilot study to test these hypotheses in patients with OHS. The investigators will enroll patients with OHS, to examine the subacute effects of KD (12 days) on OHS respiratory and neuro-endocrine physiology.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Ketogenic Diet for Obesity Hypoventilation Syndrome
Estimated Study Start Date : October 2019
Estimated Primary Completion Date : August 2021
Estimated Study Completion Date : August 2021

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.




Primary Outcome Measures :
  1. Change in Awake venous carbon dioxide (PaCO2) Level [ Time Frame: Baseline (pre keto diet) and 2 weeks post keto diet ]
    Measured in mmHg.


Secondary Outcome Measures :
  1. Change in Venous pH [ Time Frame: Once per week, over 4 weeks ]
    Measured in moles per liter.

  2. Change in Glucose level [ Time Frame: Once per week, over 4 weeks ]
    Measured in g/dL.

  3. Change in Insulin level [ Time Frame: Once per week, over 4 weeks ]
    Measured in mIU/L.

  4. Change in leptin level [ Time Frame: Once per week, over 4 weeks ]
    Measured in ng/mL.

  5. Change in beta-Hydroxybutyrate level [ Time Frame: Once per week, over 4 weeks ]
    Measured in mg/dL.

  6. Glucose profile [ Time Frame: Continuously measured over 4 weeks ]
    Using continuous glucose monitoring (CGM), to measured glucose level (g/dL) each day at home.

  7. Change in Body weight (kg) [ Time Frame: Once per week, over 4 weeks ]
  8. Change in Oxygen saturation [ Time Frame: Once per week, over 4 weeks ]
    Measured as a percentage.

  9. Change in Blood Pressure [ Time Frame: Once per week, over 4 weeks ]
    Measured in mmHg.

  10. Change in percentage of body fat [ Time Frame: Once every 2 weeks, over 4 weeks ]
    The investigators will measure percentage body fat using the Bioelectrical impedance analysis (BIA).

  11. Change in Apnea Hypopnea Index [ Time Frame: Once every 2 weeks, over 4 weeks ]
    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.

  12. Change in LDL Cholesterol [ Time Frame: Once per week, over 4 weeks ]
    Measured in mg/dL.

  13. Change in HDL Cholesterol [ Time Frame: Once per week, over 4 weeks ]
    Measured in mg/dL.

  14. Change in Triglyceride level [ Time Frame: Once per week, over 4 weeks ]
    Measured in mg/dL.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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
  • 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:

  • Diabetes (type 1 or 2) requiring use of insulin or insulin secretagogues (glyburide, glipizide, glimepiride, repaglinide, nateglinide)
  • Concomitant participation in another weight loss or diet program
  • Patients with incomplete OSA 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04108819


Contacts
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Contact: David Kim, MD 410-550-8773 dkim205@jhmi.edu
Contact: Jonathan Jun, MD jjun2@jhmi.edu

Locations
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United States, Maryland
Johns Hopkins Bayview Medical Center Recruiting
Baltimore, Maryland, United States, 21224
Sponsors and Collaborators
Johns Hopkins University
Investigators
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Principal Investigator: Jonathan Jun, MD Johns Hopkins University

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Responsible Party: Johns Hopkins University
ClinicalTrials.gov Identifier: NCT04108819     History of Changes
Other Study ID Numbers: IRB00212924
First Posted: September 30, 2019    Key Record Dates
Last Update Posted: September 30, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Respiratory Insufficiency
Hypoventilation
Obesity Hypoventilation Syndrome
Obesity
Syndrome
Disease
Pathologic Processes
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Sleep Apnea, Obstructive
Sleep Apnea Syndromes
Apnea
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Wake Disorders
Nervous System Diseases