Clinical trial NCT00435643: Influence of nCPAP on Metabolic Consequences Associated With OSAS
Official title: Improvement in Hypothalamic-Pituitary-Adrenal Axis Function After Continuous Positive Airway Pressure Therapy in Obstructive Sleep Apnea Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obstructive Sleep Apnea Syndrome
Obesity
Keywords: Sleep apnea,
adiponectin ,
HPA axis
Lead sponsor: Federal University of São Paulo
Sponsor class: OTHER
First posted: 2007-02-15
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: Context: Obstructive sleep apnea syndrome (OSAS) is associated with cardiovascular morbidity. Recurrent episodes of occlusion of upper airways during sleep result in hormonal changes that may predispose to high cardiovascular risk.These risks can rapidly be reduced by effective nasal continuous positive airway pressure (nCPAP) therapy Objective: To evaluate hypothalamic pituitary adrenal axis, insulin resistance, blood pressure values and adipokines in severe obese patients with and without OSAS and to determine if continuous positive airway pressure therapy (nCPAP) influenced responses.

Detailed description: Background: There is evidence that obstructive sleep apnea syndrome (OSAS) increases the risk of cardiovascular events. Sympathetic nervous system and hypothalamic-pituitary-adrenal (HPA) axis activation may be the mechanism of this relationship. We evaluate HPA axis and metabolic consequences in obese patients with and without OSAS and we determine if continuous positive airway pressure therapy (nCPAP) influenced responses.

Methods: Plasma inflammatory cytokines, insulin resistance index, 24-hour ambulatory blood pressure monitoring and overnight cortisol suppression test with 0.25 mg of dexamethasone were performed in 22 severe obese patients with OSAS and 23 obese controls. Ten patients with severe apnea were re-evaluated three months after nCPAP therapy.

Results: Body mass index, abdominal circumference, blood pressure levels and insulin resistance indexes of OSAS patients and obese controls were very similar. In OSAS patients, adiponectin (p\<0.05) and salivary cortisol suppression pos DEX (p\<0.05) were lower, while heart rate (p\<0.05) and TNF-alpha levels (p\<0.05) were higher compared with obese controls. After nCPAP therapy, patients showed a reduction in heart rate (p=0.036) and a higher cortisol suppression after dexamethasone (p=0.001) and there were no differences in insulin resistance (HOMA p=0.139), arterial blood pressure (p=0.183) and adipokines compared with baseline. Cortisol suppression was positively correlated with the improvement of apnea hypopnea index while on nCPAP therapy (r= 0.799, p=0.010).

Conclusions: Patients with OSAS present nocturnal hypercortisolism, hyperactivity of sympathetic central nervous system, a higher degree of inflammation and hypoadiponectinemia independent of the body mass index. Furthermore, hyperactivity of HPA axis and sympathetic nervous system are recovered by nCPAP.

Eligibility criteria: Inclusion Criteria:

* Aged from 18 to 65 years
* Body mass index between 35-60 who were submitted to polysomnography

Exclusion Criteria:

* History of smoking
* Sleep apnea treatment
* Cardiovascular disease
* Malignancies tumor
* Thyroid disorders
* Depression
* Subjects with known diabetes mellitus on medications
* Chronic renal or hepatic failure
* On hormonal replacement therapy, as well as use of medication that could potentially affect steroid hormone or cytokines secretion (alcohol, psychotropics, steroids, sympathomimetics, beta-blockers).

Primary outcomes:
measure: To explore the interactive mechanisms of HPA axis, sympathetic nervous system activation, inflammatory cytokines, insulin resistance and hypertension in patients with and without sleep apnea, excluding the interference of the degree of fat accumulation.
timeFrame: one day
Secondary outcomes:
measure: To evaluate low-dose dexamethasone-induced cortisol suppression and circadian rhythm of cortisol secretion in severe obese patients with sleep apnea in response to treatment with continuous positive airway pressure.
timeFrame: three months
Other outcomes:
Locations:
city: Sao Paulo
country: Brazil
facility: Universidade Federal de Sao Paulo
state: SP
Study officials:
affiliation: UNIFESP-EPM
name: Gláucia Carneiro, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Carneiro G, Florio RT, Zanella MT, Pradella-Hallinan M, Ribeiro-Filho FF, Tufik S, Togeiro SM. Is mandatory screening for obstructive sleep apnea with polysomnography in all severely obese patients indicated? Sleep Breath. 2012 Mar;16(1):163-8. doi: 10.1007/s11325-010-0468-7. Epub 2011 May 29.