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

Obesity Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02419092
• Other study ID #: LIRMOI-5-OSA
• Status: Completed
• Phase: N/A
• First received: March 30, 2015
• Last updated: October 16, 2017
• Start date: April 2015
• Est. completion date: September 19, 2017

Study information

• Verified date: January 2016
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: September 19, 2017
• Est. primary completion date: September 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Apnea
• Inflammation
• Obesity
• Obstructive Sleep Apnea
• Sleep Apnea Syndromes
• Sleep Apnea, Obstructive
• Weight Loss

Locations

Country	Name	City	State
Denmark	Aarhus University Hospital	Aarhus C

Sponsors (1)

Lead Sponsor	Collaborator
University of Aarhus

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Arterial stiffness assessed by office carotid-femoral pulse-wave	Changes in arterial stiffness assessed by office carotid-femoral pulse-wave velocity	Evaluated at baseline, end of intervention and 6 months post-bariatric surgery
Primary	Metabolic changes in adipose and liver tissue induced by OSA. Obese subjects with OSA will be compared to obese subjects without OSA.	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)	Biopsies and blood samples obtained in relation to bariatric surgery
Secondary	Effect of bariatric surgery on adipose tissue inflammation and systemic inflammation.	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.	Evaluated at time of bariatric surgery and at follow-up 6 months after bariatric surgery.
Secondary	Effect of bariatric surgery on insulin sensitivity.	Changes in insulin sensitivity assessed by HOMA-IR, fructosamine and correction in oral anti diabetic medication.	Evaluated at time of bariatric surgery and at follow-up 6 months after bariatric surgery
Secondary	Effect of bariatric surgery on the severity of OSA.	Changes in AHI-score and Sleepiness Score (based on questionnaires).	Evaluated at baseline, 4 weeks post-bariatric surgery and 6 months post-bariatric surgery