Advertisement

Topics

Impact of Obstructive Sleep Apnea Syndrome on Metabolic Syndrome in Severe Obesity

2014-07-23 21:11:25 | BioPortfolio

Summary

The aim of this project is to study the relationship between obstructive sleep apnea (OSA) and metabolic syndrome (MS) in a population of obese patients who are candidates for bariatric surgery. The investigators will study the influence of OSA through hypoxia and sleep fragmentation on different proinflammatory adipokines and cytokines, on metabolic syndrome and on insulin resistance, as well as how these respond to treatment with continuous positive airway pressure (CPAP).

In the first part of the study (part A) the investigators will perform an observational study of cases and controls. Based on the diagnostic polysomnography the patients will be divided into two groups depending on their apnea-hypopnea index (AHI): OSA (AHI >= 15/h) and non-OSA (AHI <15/h). The results will be analyzed depending on the presence or not of OSA.

In the second part of the study (part B), the patients with severe OSA (AHI ≥ 30/h) will be randomized into two groups: one group will receive CPAP + diet treatment and the other group will only receive diet treatment. After 3 months of treatment (CPAP + diet vs. diet), the investigators will analyze the overall effect on metabolic syndrome and the effect on its individual components, as well as the above-mentioned inflammatory pathways and insulin sensitivity, between the 2 groups. This will be carried out through a randomized controlled study in which the investigators will compare the effect of CPAP with the effect of conservative treatment.

Description

METHODOLOGY

PARTICIPATING CENTERS: Respiratory Medicine and Endocrinology Services of the Hospital Universitari de Bellvitge, of the Hospital de la Santa Creu i Sant Pau and of Hospital Clínic de Barcelona.

PATIENTS (recorded in eligibility criteria)

Ethical aspects: All patients will be asked for informed consent in accordance with the procedures of the Ethical Committee of the hospitals. Patients will be recruited in the initial stage of the protocol and waiting list for bariatric surgery. Currently the waiting list is 2 to 3 years long and the patients are screened for OSA in the year before the intervention, with the aim of treating OSA patients in order to reduce the perioperative surgical risk. Therefore the protocol will not lead to a delay in the start of treatment, since treatment will be commenced earlier than usual. Once the study period is over, the patients in the control group will receive CPAP if necessary.

DESIGN:

Multi-center study (with the participation of 3 centers), with an initial part (A) that is an observational prospective case-control study coordinated by the Hospital Universitari de Bellvitge. Based on the polysomnography performed on all patients who fulfill the inclusion criteria, the patients will be put into two groups: CASES: patients with OSA (AHI >= 15) and CONTROLS: Non-OSA (AHI < 15). We will analyze whether metabolic syndrome is present or not and the different determinations depending on whether or not the patients have OSA. In the second part of the study (B) coordinated by the Hospital de la Santa Creu i Sant Pau we will analyze the treatment response of OSA patients with AHI >= 30 to CPAP with a prospective, controlled and randomized study of parallel groups, in which CPAP treatment will be compared with conservative treatment in the form of a diet.

Sample Size:

In the observational study (part A), based on previous studies and accepting an alpha risk of 0.05 and a beta risk of 0.20 in bilateral contrast, we calculated that 39 subjects are needed in each group to detect a difference greater than or equal to 0.32 between them. A proportion of 0.55 is assumed in one of the groups. The dropout rate for the study has been estimated at 10%. The ARCCOSINE approximation has been used.

In the treatment response study (part B), 63 subjects are needed in each group to detect a difference that is greater or equal to 1 units of HOMA, assuming a standard deviation of 1.90 based on previous studies. The dropout rate for the study has been estimated at 10%.

STUDY VARIABLES:

1. Anthropometric and demographic data: age, sex, weight, height, BMI, neck circumference. Time between when patient became obese and recruitment date (period of obesity).

2. Measures of central obesity: waist circumference (above the superior border of the iliac crest). The body mass index will be determined by dividing the weight in kilograms by the height in meters squared. The waist/hip ratio will be measured.

3. Body fat composition will be measured with electrical bioimpedance using the Bioimpedance Meter BIA 101 (Akern Bioresearch, Florence, Italy), with an analyzer for bioimpedance of the vectors R (resistance) and Xc (reactance) with reference values for obese subjects (Piccoli A. et al. Int. Journ. Of Obesity 1998; 22:97-104).

4. General clinical questionnaire: cardiovascular risk factors and co-morbidity.

5. Self-assessment of daytime sleepiness. This will be analyzed using the Epworth scale (MW Johns, Sleep 1991, 14;540).

6. Degree of sleepiness according to the definition of the American Thoracic Society: classification into three categories: light, moderate and severe somnolence.

7. Hours of sleep: this will be analyzed using a sleep diary that will be kept during a period of 15 consecutive days. In addition, basic questions will be asked of each patient while obtaining the medical history about the usual hours of sleep on working days and weekends and holidays.

8. Physical activity questionnaire: international self-administered questionnaire of physical activity, short version. International physical activity questionnaire (IPAQ) www.ipaq.ki.se.

9. Questionnaire on quality of life in patients with sleep apnea Quebec Sleep Questionnaire (QSQ), self-administered, version translated into Spanish. (Y Lacasse, Thorax 2004).

10. Respiratory Function Study: maximum F/V loop performed with Datospir 500 spirometer (SIBEL, Barcelona), in accordance with the norms and reference values of the SEPAR (Roca et al. Bull Eur Physiopathol Respir, 1986, 22: 217-24). In addition to the spirometric variables (FVC; FEV1, FEV1/FVC,PEF), MIF50, MEF50/MIF50, PEF/FEV1 FEV0,5/FEV1, VVM/FEV1 will also be assessed. Static lung volumes. Helium dilution technique in accordance with the norms and reference values of the SEPAR (Roca el al. Bull Eur Physiopathology Respir, 1986, 22: 217-224). Arterial gases will be taken at rest while the subject is seated and breathing room air and they will be evaluated using the established recommendations (SEPAR working group for the practice of arterial gasometry (Arch. Bronconeumol 1998: 34: 142-151).

11. Conventional Polysomnography (PSG). This will be performed over an entire night using a Compumedics Siesta Polysomnograph (Compumedics, Melbourne, Australia). It will include 2 electroencephalogram channels, 2 electro-oculography channels, chin electromyography, oronasal flow measured by a thermistor and nasal canula, thoracic and abdominal excursion bands, oxyhaemoglobin saturation (SpO2) measured with a finger probe, electrocardiogram, anterior tibial electromyogram, sound recording for snores, and a body position sensor. The criteria of Rechtstaffen and Kales will be used for visual scoring of sleep stages. The minimum recording time is 6 hours and the minimum sleep time is 3 hours. Definition of apnea: absence of flow for at least 10 seconds. Definition of hypopnea: any reduction of flow with a minimum duration of at least 10 seconds that is accompanied by a desaturation (greater or equal to 3%) and/or a transitory awakening or arousal (with arousal defined according to ASDA criteria: Sleep, 1992; 15: 173-184). Definition of hypoventilation: prolonged periods of arterial desaturation not preceded by episodes of respiratory events. The following data will be recorded: number of apnea/hypopnea episodes per hour (AHI), percentage of time in apnea and/or hypopnea, number of arousals/hour, sleep efficiency (total sleep time/length of recording), percentage of time in phases 1, 2, 3-4 and REM, initial oxyhemoglobin saturation, average of oxyhemoglobin saturation, minimum saturation, time with saturation of oxyhemoblobin under 90 % (CT90) and 85 % (CT85).

12. Blood tests: a blood sample will be taken from all patients to determine their biochemical profile and full general blood count, lipid profile (Triglycerides, cholesterol (total cholesterol, HDL, VDL, LDL), glycosylated hemoglobin, insulin, leptin, TNF alpha, TNF alpha soluble receptors 1 and 2, IL-6, IL-8 and adiponectin.

13. Measurement of blood pressure: The morning after the PSG is carried out 2 blood pressure measurements will be taken at rest in a supine position, separated by 5 minutes, and additional measurements will be made if there is a difference of more than 5 mmHg between them. In accordance with the rules of the Sociedad Española de Hipertensión. (Hipertension 2005; 22 supl 2: 16-20)

14. Calculation of insulin resistance: This will be performed using the HOMA calculation (Homeostasis Model Assessment) modeled by Matthews et al (Diabetologia 1985; 28: 412-419.).

15. Glucose tolerance measurements: In those patients without recognized diabetes mellitus, a glucose load will be given after 12 hours of fasting, by administering 75 g of glucose and determining glucose levels at 0 and 120 minutes.

16. Metabolic Syndrome: The percentage of Metabolic Syndrome will be defined for each of the groups, with Metabolic Syndrome defined in accordance with international criteria (Adult Treatment Panel III. JAMA 2001; 2486-2497) as the existence of the following three conditions: 1) Central obesity: waist > 88 cm in women, > 102 cm in men, 2) Arterial hypertension: AHT greater than or equal to 130/85 mmHg or treatment, 3) Hyperglycemia: plasma glucose > 6.1 mmol/L, 4) Hypertriglyceridemia: TG greater than 1.7 mmol/L, 5) Hypo-HDL: HDL less than 1.3 mmol/L in men and 1 mmol/L in women. A metabolic index will be established for each subject that will define the number of individual components of Metabolic Syndrome they present.

PROCEDURE:

Part A: All patients from the obesity surgery program of the Endocrinology service that fulfill the inclusion criteria will be recruited. Patients will be assigned to groups according to the result of the polysomnography. Patients with AHI >= 15 will be considered OSA and all other patients non-OSA until there are 39 patients in each group, in accordance with the sample calculation. Thus all patients will be evaluated at baseline according to their condition of OSA/non-OSA.

Part B: Subsequently, the patients with severe OSA (AHI>=30) who do not fulfill the specific exclusion criteria for part B will randomized into the group for treatment with CPAP and diet or the group for conservative treatment (diet). The patients will be evaluated after 6 and 12 weeks from the start of treatment (CPAP and diet vs. diet). The variables will be determined at baseline and after 12 weeks.

STATISTICAL ANALYSIS:

A descriptive analysis of the sample will be carried out in accordance with central tendency measures (mean, median) and dispersion measures (standard deviation and interquartile range) in accordance with normality criteria (Kolmogorov-Smirnov test). Then a comparative study will be performed between the groups using chi-square test or Fisher's exact test as appropriate to the qualitative variables; and Student's t test or the Mann-Whitney U test will be used for the quantitative variables according to normality criteria.

The percentages of metabolic syndrome in the OSA and non-OSA patients, as well as the percentages of OSA in the groups with and without metabolic syndrome will be compared. The differences in metabolic syndrome and the metabolic index will be analyzed according to the severity of the OSA. This will initially be carried out through the univariate analysis of the variables gathered in the group of patients and the control groups, and those variables that have an association with p-value < 0.10, and that do not interact among themselves will be considered in a binary logistic regression model.

In the second part of the study, after 12 weeks of CPAP treatment, the variables from the baseline and final situation will be compared with the parametric or non-parametric tests as appropriate depending on their normality.

The analysis will be carried out using the statistical package SPSS 15.0 (Illinois, Chicago), and a p-value < 0.05 will be considered statistically significant in all cases.

Study Design

Allocation: Randomized, Control: Active Control, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Conditions

Metabolic Syndrome

Intervention

CPAP, Diet

Location

Hospital Universitari de Bellvitge
Hospitalet de Llobregat
Barcelona
Spain
08907

Status

Active, not recruiting

Source

Hospital Universitari de Bellvitge

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-07-23T21:11:25-0400

Clinical Trials [2699 Associated Clinical Trials listed on BioPortfolio]

Impact of a Nutritional Intervention on Type1 Diabetes Adult With Metabolic Syndrome

Recent studies have found that up to 45 % of patients with type 1 diabetes have metabolic syndrome, a cluster of conditions (abdominal obesity, hypertension, dyslipidemia, insulin resistan...

Prevalence of Metabolic Syndrome in Obstructive Sleep Apnea (OSA) and Effect of Treatment With Continuous Positive Airway Pressure (Auto-CPAP) on Metabolic Syndrome

Metabolic syndrome is a constellation of risk factors for cardiovascular disease. The prevalence of metabolic syndrome in persons with obstructive sleep apnea syndrome (OSAS) is known to b...

Wholegrain Cereal Diet and Insulin Sensitivity

A diet with the multiple beneficial characteristics of whole grains and, more in general, of "healthy cereals" favorably influences glucose and insulin metabolism in subjects with metaboli...

Effects of Low and Moderate Fat Diets on Lipids, Inflammation and Vascular Reactivity in the Metabolic Syndrome

The metabolic syndrome consists of five concurrent conditions which increase risk of heart disease, stroke, and diabetes. Persons with the metabolic syndrome usually have high triglyceride...

Methionine-Restriction Diet (MRD) in Obese Adults With Metabolic Syndrome

The purpose of this study is to determine if limiting dietary methionine (MET), one of the 10 essential amino acids (which make up proteins), causes weight loss and/or improves glucose met...

PubMed Articles [10341 Associated PubMed Articles listed on BioPortfolio]

Exercise, diet and educational interventions for metabolic syndrome in persons with schizophrenia: A systematic review.

Individuals with major psychotic disorders such as schizophrenia are at increased risk for developing metabolic syndrome due to lifestyle- and treatment-related factors. Numerous interventions have be...

Influence of a structured follow-up on CPAP adherence in patients with an OSAS.

Continuous positive airway pressure (CPAP) therapy is the reference therapy for moderate and severe obstructive sleep apnea syndrome (OSAS). However, CPAP adherence is dissatisfying. We analyzed influ...

A ketogenic diet reduces metabolic syndrome-induced allodynia and promotes peripheral nerve growth in mice.

Current experiments investigated whether a ketogenic diet impacts neuropathy associated with obesity and prediabetes. Mice challenged with a ketogenic diet were compared to mice fed a high-fat diet or...

Diet associated with exercise improves baroreflex control of sympathetic nerve activity in metabolic syndrome and sleep apnea patients.

We tested the hypothesis that (i) diet associated with exercise would improve arterial baroreflex (ABR) control in metabolic syndrome (MetS) patients with and without obstructive sleep apnea (OSA) and...

Metabolic syndrome and psoriasis: a study in 97 patients.

Psoriasis is associated with higher prevalence of metabolic syndrome (MS). The prevalence of MS varies according to the studied population as it suffers influence of genetics, aging, sedentary behavio...

Medical and Biotech [MESH] Definitions

A diet that contains limited amounts of fat with less than 30% of calories from all fats and less than 10% from saturated fat. Such a diet is used in control of HYPERLIPIDEMIAS. (From Bondy et al, Metabolic Control and Disease, 8th ed, pp468-70; Dorland, 27th ed)

A cluster of metabolic risk factors for CARDIOVASCULAR DISEASES and TYPE 2 DIABETES MELLITUS. The major components of metabolic syndrome X include excess ABDOMINAL FAT; atherogenic DYSLIPIDEMIA; HYPERTENSION; HYPERGLYCEMIA; INSULIN RESISTANCE; a proinflammatory state; and a prothrombotic (THROMBOSIS) state. (from AHA/NHLBI/ADA Conference Proceedings, Circulation 2004; 109:551-556)

A cluster of symptoms that are risk factors for CARDIOVASCULAR DISEASES and TYPE 2 DIABETES MELLITUS. The major components of metabolic syndrome include ABDOMINAL OBESITY; atherogenic DYSLIPIDEMIA; HYPERTENSION; HYPERGLYCEMIA; INSULIN RESISTANCE; a proinflammatory state; and a prothrombotic (THROMBOSIS) state.

A diet that contains limited amounts of CARBOHYDRATES. This is in distinction to a regular DIET.

Regular course of eating and drinking adopted by a person or animal. This does not include DIET THERAPY, a specific diet prescribed in the treatment of a disease.

More From BioPortfolio on "Impact of Obstructive Sleep Apnea Syndrome on Metabolic Syndrome in Severe Obesity"

Advertisement
Quick Search
Advertisement
Advertisement

 

Relevant Topics

Sleep Disorders
Sleep disorders disrupt sleep during the night, or cause sleepiness during the day, caused by physiological or psychological factors. The common ones include snoring and sleep apnea, insomnia, parasomnias, sleep paralysis, restless legs syndrome, circa...

Obesity
Obesity is the condition in which excess fat has accumulated in the body (mostly in subcutaneous tissues). clinical obesity is considered to be present when a person has a BMI of over 30 (Oxford Dictionary of Medicine). It is becoming increasing common i...


Searches Linking to this Trial