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Obstructive Sleep Apnea-induced Changes in Adipose and Liver Tissue and Effects of Massive Weight Loss on Inflammation

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ClinicalTrials.gov Identifier: NCT02419092
Recruitment Status : Completed
First Posted : April 17, 2015
Last Update Posted : October 17, 2017
Sponsor:
Information provided by (Responsible Party):
University of Aarhus

Brief Summary:

UPDATED May 2016:

Originally the study design included investigation of the effects of the bioactive compound resveratrol compared to placebo tablets and to CPAP treatment. Due to fewer subjects having OSA than estimated by pre-study and, therefore, difficulties in the recruiting process the investigators have found it necessary to descale the study design. Hence, we have discontinued the resveratrol and CPAP intervention and will focus on the cross-sectional investigation of metabolic changes in subjects with and without OSA and the effect of weight loss after bariatric surgery on inflammation, OSA severity, metabolism and arterial stiffness.

Obstructive sleep apnea (OSA) is a common disorder especially among obese individuals and patients with type 2 diabetes. OSA is associated with an increased morbidity and mortality.

Continuous positive airway pressure (CPAP) is the standard treatment. Also weight loss is known to reduce the severity of OSA, especially bariatric surgery has proven effective because of the massive weight loss.

The investigators hypothesize that OSA via pro-inflammatory responses in various tissues causes low-grade inflammation which ultimately induce the associated co-morbidities. The investigators hypothesize that massive weight loss after bariatric surgery have beneficial effects on severity of OSA, inflammatory status and improves insulin sensitivity.


Condition or disease
Obesity Obstructive Sleep Apnea

Detailed Description:

UPDATED May 2016:

Originally the study design included investigation of the effects of the bioactive compound resveratrol compared to placebo tablets and to CPAP treatment. Due to fewer subjects having OSA than estimated by pre-study and, therefore, difficulties in the recruiting process the investigators have found it necessary to descale the study design. Hence, we have discontinued the resveratrol and CPAP intervention and will focus on the cross-sectional investigation of metabolic changes in subjects with and without OSA and the effect of weight loss after bariatric surgery on inflammation, OSA severity, metabolism and arterial stiffness.

OSA causes insulin resistance and seems to aggravate obesity related comorbidities such as hypertension, dyslipidemia and increase the risk of development of type 2 diabetes and non-alcoholic fatty liver disease.

More mechanisms may be involved in the pathogenesis of these negative effects from OSA but hypoxia-induced low-grade inflammation may play a central role since the levels of inflammatory markers generally are elevated in OSA. The tissues which are responsible for these systemic alterations are not known, however, adipose tissue might be a good candidate since it is known from studies that human adipose tissue can influence systemic inflammation.

Some studies even describe a small but significant anti-inflammatory effect and a beneficial effect on glucose metabolism following CPAP treatment. In addition, weight loss in patients with OSA is known to reduce the severity of or completely eliminate OSA.

The purpose of this study is primarily to investigate:

  1. the metabolic changes in adipose and liver tissue induced by OSA in order to better understand how OSA negatively affects whole-body metabolism
  2. the effect of weight loss after bariatric surgery on systemic inflammation, metabolism and the severity of OSA

24 subjects scheduled to undergo bariatric surgery will be recruited. They will all be screened for OSA. 12 subjects without OSA and 12 subjects with OSA will be included and examined before surgery and 6 months post-surgery.

The investigators will look at changes in:

  • Inflammation-markers
  • Biochemical markers of fat and sugar-metabolism
  • Gene-expression in adipose and liver-tissue
  • Severity of OSA
  • Pulse-wave velocity

Study Type : Observational
Actual Enrollment : 27 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Investigation of Inflammation Induced by Obstructive Sleep Apnea: Effects of Continuous Positive Airway Pressure (CPAP), Massive Weight Loss and the Bioactive Compound Resveratrol
Study Start Date : April 2015
Actual Primary Completion Date : September 2017
Actual Study Completion Date : September 19, 2017

Resource links provided by the National Library of Medicine


Group/Cohort
Obstructive Sleep Apnea
Subjects scheduled to undergo bariatric surgery and with Obstructive Sleep Apnea
No Obstructive Sleep Apnea, controls
Subjects scheduled to undergo bariatric surgery and without Obstructive Sleep Apnea, control group



Primary Outcome Measures :
  1. Metabolic changes in adipose and liver tissue induced by OSA. Obese subjects with OSA will be compared to obese subjects without OSA. [ Time Frame: Biopsies and blood samples obtained in relation to bariatric surgery ]
    Cross-sectional genetic and metabolic analysis of biopsies and blood samples obtained in relation to bariatric surgery on subjects with and without sleep apnea. In tissue samples gene-expression profile is measured using Affymetrix gene array and blood samples are used for metabolic profiling and inflammatory markers (hs-CRP, TNFalfa, IL-6, IL-8, adiponectin, leptin, MCP-1, FGF211, CD163)


Secondary Outcome Measures :
  1. Effect of bariatric surgery on adipose tissue inflammation and systemic inflammation. [ Time Frame: Evaluated at time of bariatric surgery and at follow-up 6 months after bariatric surgery. ]

    Changes in inflammation markers (hs-CRP, TNFalfa, IL-6, IL-8, adiponectin, leptin, MCP-1, FGF21, CD163) in blood and adipose tissue.

    Changes in expression of mRNA of the relevant inflammatory pathways assessed by gene expression studies.


  2. Effect of bariatric surgery on insulin sensitivity. [ Time Frame: Evaluated at time of bariatric surgery and at follow-up 6 months after bariatric surgery ]
    Changes in insulin sensitivity assessed by HOMA-IR, fructosamine and correction in oral anti diabetic medication.

  3. Effect of bariatric surgery on the severity of OSA. [ Time Frame: Evaluated at baseline, 4 weeks post-bariatric surgery and 6 months post-bariatric surgery ]
    Changes in AHI-score and Sleepiness Score (based on questionnaires).


Other Outcome Measures:
  1. Arterial stiffness assessed by office carotid-femoral pulse-wave [ Time Frame: Evaluated at baseline, end of intervention and 6 months post-bariatric surgery ]
    Changes in arterial stiffness assessed by office carotid-femoral pulse-wave velocity


Biospecimen Retention:   Samples With DNA
Blood samples, urine, subcutaneous adipose tissue, visceral adipose tissue and liver tissue.


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Ages Eligible for Study:   25 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Study groups will be selected from subjects referred to the outpatient clinics in Central Denmark Region and who meet the national guideline criteria for bariatric surgery.
Criteria

Inclusion Criteria:

  • Female/Male
  • Legally competent (habil)
  • 25-65 years old
  • BMI > 35 and fulfill criteria for bariatric surgery in Denmark
  • Written informed consent

Exclusion Criteria:

  • Current treatment with CPAP
  • Permanent treatment with glucocorticoids, NSAID or sleeping pills (otherwise discontinued for 1 week prior to inclusion)
  • Severe heart, liver, kidney or lung disease
  • Type 1 diabetes
  • Work in transportation-related industry
  • Pregnancy
  • Substance abuse problem

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): NCT02419092


Locations
Denmark
Aarhus University Hospital
Aarhus C, Denmark, 8000
Sponsors and Collaborators
University of Aarhus
Investigators
Principal Investigator: Steen B Pedersen, MD,Professor Aarhus University Hospital

Responsible Party: University of Aarhus
ClinicalTrials.gov Identifier: NCT02419092     History of Changes
Other Study ID Numbers: LIRMOI-5-OSA
First Posted: April 17, 2015    Key Record Dates
Last Update Posted: October 17, 2017
Last Verified: January 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by University of Aarhus:
Inflammation
Insulin resistance
Bariatric surgery

Additional relevant MeSH terms:
Inflammation
Apnea
Sleep Apnea Syndromes
Weight Loss
Sleep Apnea, Obstructive
Pathologic Processes
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Wake Disorders
Nervous System Diseases
Body Weight Changes
Body Weight