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Fat Metabolism in OSA and COPD

This study is currently recruiting participants.
See Contacts and Locations
Verified April 2017 by Marielle PKJ Engelen, PhD, Texas A&M University
Sponsor:
Information provided by (Responsible Party):
Marielle PKJ Engelen, PhD, Texas A&M University
ClinicalTrials.gov Identifier:
NCT02157844
First received: June 4, 2014
Last updated: April 17, 2017
Last verified: April 2017
  Purpose

Obstructive sleep apnea (OSA) is the most common type of sleep apnea and is caused by an obstruction of the upper airways. The obstruction results in periods of intermittent hypoxia and re-oxygenation, which lead to increased oxidative stress, increased inflammation, endothelial dysfunction, and insulin resistance. Chronic obstructive pulmonary disease (COPD) is a lung disease that leads to poor airflow. This disease leads to systemic hypoxia, reduced oxidative capacity, and increased inflammation. The direct cause of OSA and COPD is unclear, but OSA and COPD may be linked to other comorbid conditions such as obesity and type II diabetes. Upon onset of OSA and COPD, metabolic disturbances associated with obesity and type II diabetes can be exacerbated.

Obesity is a condition characterized by an increase in visceral fat, elevated plasma levels of free fatty acids, inflammation, and insulin resistance. Although the effects of body fat distribution have not been studied in these patients, an increase in both subcutaneous and abdominal fat mass in non-OSA older women was shown to increase morbidity and mortality. Fat/adipose tissue is an active tissue capable of secreting proinflammatory cytokines such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-6, reactive oxygen species and adipokines. Particularly, abdominal fat is a prominent source of pro-inflammatory cytokines, which contributes to a low grade, chronic inflammatory state in these patients. Additionally, an increased inflammatory state is associated with reduced lean body mass, and together with elevated circulating free fatty acids may increase the occurrence of lipotoxicity and insulin resistance. Thus, increased fat deposition is associated with a poor prognosis in OSA and COPD patients and therefore it is of clinical and scientific importance to understand the changes in fat metabolism and digestion as a result of OSA and COPD.

It is therefore our hypothesis that fat synthesis and insulin resistance is increased and whole body protein synthesis is decreased in OSA and COPD patients, leading to a poor prognosis.


Condition
Obstructive Sleep Apnea Chronic Obstructive Pulmonary Disease Obesity

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: Fat Metabolism and Digestion in Obstructive Sleep Apnea and Chronic Obstructive Pulmonary Disease

Resource links provided by NLM:


Further study details as provided by Marielle PKJ Engelen, PhD, Texas A&M University:

Primary Outcome Measures:
  • Hepatic triglyceride synthesis [ Time Frame: Pre meal ingestion and 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210, 240, 270, and 300 min post meal ingestion ]
    changes in hepatic triglyceride synthesis before and after a meal

  • Hepatic de novo lipogenesis [ Time Frame: Pre meal ingestion and 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210, 240, 270, and 300 min post meal ingestion ]
    changes in hepatic de novo lipogenesis before and after a meal

  • Adipose tissue triglyceride synthesis [ Time Frame: pre and 4 hours post meal ]
    changes in adipose tissue triglyceride synthesis before and after a meal

  • Adipose tissue de novo lipogenesis [ Time Frame: pre and 4 hours post meal ]
    changes in adipose tissue de novo lipogenesis before and after a meal

  • Adipose tissue lipolysis - glycerol rate of appearance [ Time Frame: Pre meal ingestion and 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210, 240, 270, and 300 min post meal ingestion ]
    changes in adipose tissue lipolysis before and after a meal. plasma enrichment of glycerol.

  • Rate of appearance of ingested glucose [ Time Frame: Pre meal ingestion and 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210, 240, 270, and 300 min post meal ingestion ]
    determine changes in appearance of glucose rate in subjects

  • Endogenous Glucose Production [ Time Frame: Pre meal ingestion and 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210, 240, 270, and 300 min post meal ingestion ]
    Determine whole body glucose production in subjects

  • Glucose disposal [ Time Frame: Pre meal ingestion and 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210, 240, 270, and 300 min post meal ingestion ]
    Determine whole body glucose uptake in subjects

  • Net whole-body protein synthesis [ Time Frame: 0, 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210 min post-meal ]
    change in whole-body protein synthesis rate after intake of meal

  • Citrulline Rate of appearance [ Time Frame: Postabsorptive state during 2 hours ]
    plasma enrichment of citrulline

  • Arginine turnover rate [ Time Frame: postabsorptive state during 3 hours ]
    Arginine enrichment in plasma

  • Whole body collagen breakdown rate [ Time Frame: Postabsorptive state during 3 hours ]
    Hydroxyproline enrichment in plasma

  • Tryptophan turnover rate [ Time Frame: Postabsorptive state during 3 hours ]
    Tryptophan enrichment in plasma

  • Myofibrillar protein breakdown rate [ Time Frame: 0,15,30,45,60,75,90,105,120,150,180,210 min post-meal ]
    3methylhistidine enrichment in plasma

  • Glycine rate of appearance [ Time Frame: Postabsorptive state during 3 hours ]
    glycine enrichment in plasma

  • Taurine turnover rate [ Time Frame: postabsorptive state during 3 hours ]
    enrichment of taurine in


Secondary Outcome Measures:
  • Fat digestion and absorption [ Time Frame: Pre meal ingestion and 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210, 240, 270, and 300 min post meal ingestion ]
    defining fat digestion and absorption after a meal. Enrichment in palmitic acid and tripalmitin fatty acids in plasma

  • Insulin response to feeding [ Time Frame: pre and up to 5 hours post meal ]
    acute changes from postabsorptive state to postprandial state

  • Body composition [ Time Frame: 1 day ]
    body composition will be determined by dual-energy X-ray absorptiometry and by deuterated water dilution technique. Plasma deuterium enrichments will be determined.

  • Physical activity questionnaire [ Time Frame: 1 day ]
    Outcome of physical activity assessment in breast cancer patients and healthy controls in relation to the fat metabolism

  • Protein digestion after feeding [ Time Frame: 0,15,30,45,60,75,90,105,120,150,180,210, min post-meal ]
    Ratio enrichment free phenylalanine vs phenylalanine from protein spirulina


Biospecimen Retention:   Samples With DNA
Urine, adipose tissue, serum, plasma

Estimated Enrollment: 65
Study Start Date: April 2014
Estimated Study Completion Date: February 2019
Estimated Primary Completion Date: February 2018 (Final data collection date for primary outcome measure)
Groups/Cohorts
COPD non obese
Lean COPD subjects will be compared to COPD obese subjects
COPD Obese
Obese COPD subjects will be compared to non obese COPD subjects
OSA obese
Obese OSA subjects will be compared to non obese healthy controls
Obese controls
Obese controls will be compared to non healthy obese controls
Non obese controls
Non obese healthy controls will be compared to obese controls

Detailed Description:
This research study involves 3 visits for subjects and healthy controls. The first visit is the screening visit and includes review of the informed consent and a DXA scan and the second and third visit for the study days. For the first test day, 3 hours of the subjects time will be for urine and blood sample collection, and to stable isotope administration (deuterated water, isotopically labeled amino acids). Subjects are allowed to go home after and eat normally. On the second study day, subjects will arrive early that morning. For the duration of the study, subjects have to lie in the bed (except for bathroom privileges). They can watch tv or bring and use a book/tablet. The research nurse or study staff will be present in the human subject area to assist the subject if necessary. Subjects are not allowed to eat or drink during the second test day, except for the test drink (meal) and water. One IV catheter will be placed in a vein of the arm/hand for blood draws. The hand will be placed in a hot box during blood collection. Another IV catheter will be placed in the contra-lateral forearm for a primed and continuous infusion of isotopes (isotopically labeled amino acids and glycerol). Each day, a total of 80-100 ml of blood will be obtained. Stable isotopes will be ingested and infused on the first test day and added to the test drinks and infused on the second day. On the second test day, subjects will fill out questionnaires. After completion of the study, we will provide the subject with a meal.
  Eligibility

Ages Eligible for Study:   30 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population
Subjects with OSA or COPD will be recruited when visiting a medical or pulmonary clinic in and outside the surrounding area of College Station. Patients and healthy subjects will also be recruited by responding to distributed flyers in the community in the College Station area; for example in hospital/clinic waiting areas, clinic rooms and bulletin boards at Scott & White and the CSMC or any other hospital. Other general recruitment material in relation to the nutrition research that the research group performs at Texas A&M can be placed on bulletin boards at Scott & White and the CSMC.
Criteria

Inclusion criteria subjects:

  • Established diagnosis of OSA or COPD
  • Ability to sign informed consent
  • Ability to walk, sit down and stand up independently
  • Age 30 years and older
  • Ability to lie in supine position for up to 8 hours
  • Clinically stable condition and not suffering from a respiratory tract infection or exacerbation of their disease
  • Willingness and ability to comply with the protocol

Inclusion criteria healthy normal weight and obese subjects:

  • Healthy male & female according to the investigator's or appointed staff's judgment
  • Ability to walk, sit down and stand up independently
  • Age 30 years or older
  • Ability to lay in supine or elevated position for 8 hours
  • No diagnosis of OSA or COPD
  • Willingness and ability to comply with the protocol

Exclusion Criteria

  • Established diagnosis of malignancy
  • Untreated metabolic diseases including hepatic or renal disorder
  • Presence of acute illness or metabolically unstable chronic illness
  • Presence of fever within the last 3 days
  • Any other condition according to the PI or study physician that would interfere with proper conduct of the study / safety of the patient
  • Use of long-term oral corticosteroids or short course of oral corticosteroids in the preceding month before enrollment
  • Use of protein or amino acid containing nutritional supplements within 5 days of first study day 5 days of first study day
  • Failure to give informed consent or Investigator's uncertainty about the willingness or ability of the subject to comply with the protocol requirements
  • History of hypo- or hyper-coagulation disorders, including use of a Coumadin derivative, history of deep venous thrombosis (DVT), or pulmonary embolism (PE) at any point in lifetime
  • Currently taking anti-thrombotics and cannot stop for 7 days (i.e. medical indication)
  • Recent myocardial infarction ( < 1 year ago)
  • Current alcohol or drug abuse
  • (Possible) pregnancy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02157844

Contacts
Contact: Marielle Engelen, Ph.D. 9792202282 mpkj.engelen@ctral.org
Contact: Dillon Walker, Ph.D. 9795871082 dk.walker@tamu.edu

Locations
United States, Texas
Texas A&M University Recruiting
College Station, Texas, United States, 77843
Contact: Marielle Engelen, Ph.D.    979-220-2282    mpkj.engelen@ctral.org   
Contact: Dillon Walker, Ph.D.    9795871082    dk.walker@tamu.edu   
Principal Investigator: Marielle Engelen, Ph.D.         
Sponsors and Collaborators
Texas A&M University
Investigators
Principal Investigator: Marielle Engelen, Ph.D. Texas A&M University
  More Information

Responsible Party: Marielle PKJ Engelen, PhD, Associate Professor, Texas A&M University
ClinicalTrials.gov Identifier: NCT02157844     History of Changes
Other Study ID Numbers: 2013-0878F
Study First Received: June 4, 2014
Last Updated: April 17, 2017

Keywords provided by Marielle PKJ Engelen, PhD, Texas A&M University:
Obstructive Sleep Apnea
Chronic Obstructive Pulmonary Disease
Obesity
Hepatic fat metabolism
fat digestion
whole body protein synthesis
protein digestion
amino acid metabolism
adipose tissue fat metabolism
lipolysis

Additional relevant MeSH terms:
Lung Diseases
Apnea
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Sleep Apnea Syndromes
Sleep Apnea, Obstructive
Respiratory Tract Diseases
Respiration Disorders
Signs and Symptoms, Respiratory
Signs and Symptoms
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Wake Disorders
Nervous System Diseases

ClinicalTrials.gov processed this record on June 22, 2017