Influence of nCPAP on Metabolic Consequences Associated With OSAS

Obesity Clinical Trial

Official title:

Improvement in Hypothalamic-Pituitary-Adrenal Axis Function After Continuous Positive Airway Pressure Therapy in Obstructive Sleep Apnea Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00435643
• Other study ID #: 12383
• Status: Completed
• Phase: N/A
• First received: February 14, 2007
• Last updated: November 19, 2007
• Start date: October 2004
• Est. completion date: March 2006

Study information

• Verified date: November 2007
• Source: Federal University of São Paulo
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: National Committee of Ethics in Research
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: March 2006
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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).

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Obesity
• Obstructive Sleep Apnea Syndrome
• Sleep Apnea Syndromes
• Sleep Apnea, Obstructive

Intervention

Procedure:
• nasal continuous positive airway pressure
After an average interval of three months, 10 patients with severe OSAS (AHI of more than 30 events per hour of sleep) treated with a mean nCPAP pressure of 11.2 ± 0.7 cm of H2O were reassessed and all mentioned measurements above were repeated

Locations

Country	Name	City	State
Brazil	Universidade Federal de Sao Paulo	Sao Paulo	SP

Sponsors (1)

Lead Sponsor	Collaborator
Federal University of São Paulo

Country where clinical trial is conducted

Brazil, 

References & Publications (5)

Buckley TM, Schatzberg AF. On the interactions of the hypothalamic-pituitary-adrenal (HPA) axis and sleep: normal HPA axis activity and circadian rhythm, exemplary sleep disorders. J Clin Endocrinol Metab. 2005 May;90(5):3106-14. Epub 2005 Feb 22. Review. — View Citation

Degawa-Yamauchi M, Moss KA, Bovenkerk JE, Shankar SS, Morrison CL, Lelliott CJ, Vidal-Puig A, Jones R, Considine RV. Regulation of adiponectin expression in human adipocytes: effects of adiposity, glucocorticoids, and tumor necrosis factor alpha. Obes Res. 2005 Apr;13(4):662-9. — View Citation

Lanfranco F, Gianotti L, Pivetti S, Navone F, Rossetto R, Tassone F, Gai V, Ghigo E, Maccario M. Obese patients with obstructive sleep apnoea syndrome show a peculiar alteration of the corticotroph but not of the thyrotroph and lactotroph function. Clin Endocrinol (Oxf). 2004 Jan;60(1):41-8. — View Citation

Masserini B, Morpurgo PS, Donadio F, Baldessari C, Bossi R, Beck-Peccoz P, Orsi E. Reduced levels of adiponectin in sleep apnea syndrome. J Endocrinol Invest. 2006 Sep;29(8):700-5. — View Citation

Wolk R, Svatikova A, Nelson CA, Gami AS, Govender K, Winnicki M, Somers VK. Plasma levels of adiponectin, a novel adipocyte-derived hormone, in sleep apnea. Obes Res. 2005 Jan;13(1):186-90. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		one day
Secondary	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.		three months