Cost-effectiveness Study of a Lifestyle Change Program for the Treatment of OSA and Obesity: Hospital-Primary Care.
Condition: Obstructive Sleep Apnea of Adult; Obesity; Lifestyle; Weight Loss
MeSH terms: Apnea; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Obesity; Weight Loss
Study type: Interventional

Summary: 
      Obesity is the main risk factor for Obstructive Sleep Apnea (OSA). Nasal CPAP is the standard
      treatment for OSA, but since weight-loss programs are not usually offered to OSA patients,
      the root causes of their illness and its comorbidities are not treated. There is some
      evidence regarding improvements in OSA after weight reduction but whether weight reduction
      programs are cost-efficient has not as yet been addressed. OBJECTIVE: To determine whether an
      intensive weight-loss program, carried out in a project combining hospital and primary care
      levels, is cost-effective in the medium and long term for the treatment of obese patients
      with severe OSA undergoing CPAP treatment. More concretely, our objective is to demonstrate
      whether this program achieves sufficient improvement in OSA to allow a reduction <30/h in the
      apnea-hypopnea index in at least 25%, improving their metabolic profile and central obesity.
      METHOD: A prospective, randomized, controlled study. Control group: standard dietary
      recommendations.

      Intervention group: 0-3 months very low calorie diet, 15 days substituting three meals for
      low calorie shakes, from 15 to 120 days substituting 1 meal and from 120 days to 12 months on
      a low calorie diet while starting a progressive exercise program. Recommendations for good
      sleep habits will be given. The program will be carried out through group and individual
      sessions with the hospital dietician. After 3 months: group sessions with a nurse in the
      basic area. Group sessions led by hospital dietician. From 3 to 12 months: group sessions led
      by primary care nurse. MEASUREMENTS: At the beginning, at 3 and at 12 months: two-night home
      respiratory polygraph, actigraphy, anthropometric and blood analysis data including metabolic
      syndrome and inflammatory markers, and health related quality of life questionnaires. Direct
      and indirect costs of treatments, outpatient's consultations, incomes, emergency visits and
      patients' travel costs to medical centers.
    

Detailed description: 
      HYPOTHESIS The implementation of an intensive weight loss program, initiated under the
      supervision of an expert nutritionist and continued under the supervision of a trained
      primary care nurse can help obese patients with severe obstructive sleep apnea (OSA)
      undergoing continuous positive airway pressure (CPAP) treatment to achieve significant weight
      loss and will result in a reduction in OSA severity in a significant percentage of patients
      leading to the possibility of their ceasing CPAP treatment.

      The program will also improve the control of comorbidities, hypertension, diabetes and
      dyslipidemia and inflammation.

      OBJECTIVES

      Primary objective Assess whether a lifestyle change program, carried out in a combined and
      coordinated way with the hospital and primary care environments, can be cost-effective in the
      medium and long term for the treatment of OSA in obese patients with severe OSA who are
      already receiving CPAP treatment. In particular, to demonstrate that the program is able to
      achieve sufficient improvement in OSA to provide at least 25% of patients with a reduction of
      apnea hypopnea index (AIH <30/h).

      Secondary objectives Assess whether a lifestyle change program in obese patients with OSA who
      are already receiving CPAP treatment can achieve lower blood pressure levels, improve blood
      lipids and glycemic control and reduce C reactive protein and central obesity.

      Assess the OSA improvement predictor factors of an OSA improvement associated with weight
      loss.

      STUDY SETTING:

      The study will be performed at a tertiary hospital Sleep Unit and the Department of
      Endocrinology and Nutrition, and 5 primary care centers in the area of influence of the
      hospital. A community nurse and a referring physician will be selected at each center.

      The study has been approved by the hospital's Ethics Committee. All participants will give
      their informed written consent.

      All the study variables will be collected at baseline and the lifestyle change program will
      begin for patients in the treatment arm. Patients in the control group will continue with
      their regular visits. At three months and at one year after the beginning of treatment, sleep
      studies will be performed again and all of the other variables will be recorded for all of
      the patients. In order to prevent control group drop outs, at the end of the study, patients
      from the control group will invited to join the lifestyle change program.

      Sample size estimation is based on comparing the percentage of patients that meet the primary
      outcome definition (patients who achieve an apnea hypopneas index (AHI) under 30
      apneas-hypopneas per hour after 12 months of intervention) in two randomized groups. In the
      literature, no effect beyond 5% in AHI reduction has been observed with a regular dietary
      recommendation. So, in the control group, the expected percentage of patients that will meet
      the primary outcome is 2%. Kuna et al (Sleep 2013 36(5):64) observed a reduction in AHI to
      under 30 apneas-hypopneas per hour in 50% of patients undergoing an intensive diet
      intervention. In the investigators' context, with a severe population with a higher AHI at
      baseline, the investigators expect to reduce the apnea-hypopnea index (AHI) to under 30
      apneas-hypopneas per hour in 25 % of patients undergoing the intervention.

      Therefore, 90 patients (45 in each group) are required in order to have an 80% chance of
      detecting an increase in the primary outcome measure from 2% in the control group to 25% in
      the experimental group, with a significance of 5%. This estimation takes into account a
      dropout rate of 10%. The investigators will use an uncorrected chi-squared statistic to
      evaluate the null hypothesis that the primary outcome measures for experimental and control
      subjects are equal.

      Lifestyle Change Program:

      The life style change program will consist of two stages. The first will consist of a 3-month
      period of intensive diet and progressive exercise with biweekly consultations with a
      nutritionist (in groups or individually). The second stage will last for 9 months, until
      completion, with a diet that is progressively higher in calories, with more intense exercise,
      under the supervision of a community nurse. Five community nurses from the area of influence
      of our center will participate in a 6-hour course on nutrition and lifestyle interventions in
      which they will become familiarized with the educational materials used in primary care group
      visits. In the second stage, the group visits performed in primary care will reinforce the
      main hygienic-dietetic concepts introduced previously in the nutritionist sessions. After
      each group visit, a telephone meeting between the nutritionist and the community clinical
      nurse will be held to resolve doubts.

      Diet: First Phase: 3 months.

        -  First 15 days: Very low calorie diet. A diet that is very low in calories will be
           started (600-800 Kcal, based on gender and level of physical activity) with low calorie
           shakes that will substitute the three main meals (breakfast, lunch and dinner) and the
           necessary food to make up the total calorie intake.

        -  Up to week 12: 1200 Kcal diet with a low calorie shake replacing dinner. Exercising
           begins. Every nutrition session will last from 60 to 90 minutes and will be conducted by
           a nutritionist.

      The nutritionist will follow up on compliance with the program and monitor for potential
      adverse events at each visit. Also at each visit, the nutritionist will provide advice on
      diet and lifestyle, with a special emphasis on diet and exercise. Visits with the
      nutritionist will be biweekly group or individual. Group consultation will include 4 to 10
      patients. (see Chart 1 attached).

      At three months into the intervention, patients will be given dietary guidelines of 1200-1500
      kcal. These will be adapted individually by the dietician according to the nutritional
      requirements estimated by applying the Mifflin-St Jeor/Harris Benedict, formula without the
      hypercaloric shake. Calories intake will be based on the Mediterranean diet with the
      following percentages of macronutrients: 15-20 % Proteins,44-55 % carbohydrates and a maximum
      of 35% lipids (<7% saturated fatty acids <7%, 15-20% monounsaturated fatty acids, <7%
      polyunsaturated faty acids according Spanish obesity society (SEEDO).

      Second phase: 3 months to 1 year. Follow up at the Primary Health Centre (CAP) by a nursing
      team.Visits will take place every 1,5 months maintaining a group format in each center with
      an individual consultation with the nutritionist at 9 months.

      The nurse responsible for the group will lead the group sessions in which the objectives of
      the treatment will be reinforced and will record patients' anthropometric data at each
      session.

      Exercise Each training session will consist of stretching, 5-10' of warm-up (50-60% of the
      maximum HR), 40-50' of aerobic exercise performed at 70-80% of the maximum heart rate and
      5-10 'of cooling down (50-60% of the maximum HR). The practice of at least 150 minutes / week
      of moderate activity according to World Health Organization (WHO) recommendations (World
      Recommendations on Physical Activity for Health WHO-Geneva 2009) will be advised. If during
      the exercise program there are musculoskeletal complaints that are considered relevant (an
      Visual Analog Scale for pain (VAS) score ≥4 on three consecutive occasions) they will be
      visited by the rehabilitation service. In order to promote the practice of physical exercise
      and the acquisition of this habit, Discounts will be offered for local municipal gyms that
      will offer adequate physical exercise programs for obese people, monitored by
      physiotherapists or technicians.

      Control group: Patients will be managed according to the usual recommendations: The common
      written diet (designed by a hospital nutritionist) and an exercise advice will be given
      according to patient age and level of activity, without any other assessment or additional
      visits. Visits to the Sleep Disorders Unit will be scheduled to coincide with the assessments
      at 3 and 12 months, the same as for the intervention group.

      Criteria for withdrawal from the study:

        -  Onset of osteoarticular pain that prevents a patient from continuing to exercise

        -  A patient's continued refusal to follow the recommended guidelines.

      ETHICAL ISSUES: The study will be conducted in accordance with the principles of the
      Declaration of Helsinki, as well as of the Data Protection Act (Law 15/1999). All patients
      will be asked to provide informed consent, in accordance with the rules of the Ethics
      Committee at our institution. Since all of the patients will be receiving CPAP treatment,
      there should be no ethical concerns about evaluating the effectiveness of an alternative
      treatment that in principle is less effective than CPAP, in patients with severe OSA.

      STATISTICAL ANALYSIS:

      In order to evaluate the effectiveness of a change in lifestyle (diet and exercise) in obese
      patients with OSA, we will first perform a descriptive analysis of the demographic variables
      and baseline characteristics according to the number of cases and percentages for the
      qualitative variables and we will use measures of central tendency (mean, median) and
      dispersion (standard deviation and interquartile range) for the quantitative variables. In
      order to address the primary and secondary objectives of this study, we will run an
      inferential analysis comparing data at baseline, at 3 months and at one year in the two
      treatment groups. Tests for independent samples will be used in every case comparing the
      control and experimental groups). Either the chi-square test or Fisher's exact test will be
      used, as appropriate, to compare categorical variables and Student's T-test will be used to
      compare continuous variables; if the variable under study does not meet the conditions for
      the applicability of parametric tests, a non-parametric alternative, the Mann Whitney U test,
      will be used. An estimate of treatment effect in relation to the primary and secondary
      endpoints will be obtained from the confidence interval (95% CI) of the difference between
      means and percentages, as appropriate. The efficacy assessment will be based on an analysis
      of the per protocol populations (PP) and intention-to-treat (ITT), with the ITT population
      being the main analysis. For the population analysis using ITT, the missing data will be
      filled in and a sensitivity analysis will be conducted if more than one method of imputation
      is used. The PP population will be determined in accordance with compliance with visits, as
      well as with diet and exercise. A safety assessment will be made by identifying the adverse
      effects that are considered to be most significant due to their frequency or severity. In all
      cases, the significance level used will be 5% <0.05) with a bilateral approach. The
      statistical software used for the analysis will be IBM SPSS Statistics 21.

      We will carry out two cost-effectiveness analyses, since we will use two effectiveness
      variables, The Short Form-36 Health Survey (SF-36) and the % decrease in AHI below 30, in the
      population studied in patients with severe OSA with a one-year follow-up. At first the
      database will be cleaned up and the cost allocation will be carried out by applying the
      flowchart. Then the analysis will determine the cost-effectiveness ratios (ICERs)
      acceptability curves, confidence ellipses and sensitivity analysis. A study of the costs will
      also be carried out taking into account the different hidden items.
    

Intervention name(s): Intensive weigh-loss program; Standard Dietary recommendations
Intervention type(s): Behavioral; Behavioral
Intervention description(s): Intervention group: Intensive weight-loss program: 0-3 months very low calorie diet, 15 days substituting three meals for low calorie shakes, from 15 to 120 days substituting 1 meal and from 120 days to 12 months on a low calorie diet while starting a progressive exercise programme. Recommendations for good sleep habits will be given. The program will be carried out through group and individual sessions with the hospital dietician. After 3 months: group sessions with a nurse in the basic area. Group sessions led by hospital dietician. From 3 to 12 months: group sessions led by primary care nurse.; Patients will be managed according to the usual recommendations: The common written diet (designed by a hospital nutritionist) and an exercise advice will be given according to patient age and level of activity, without any other assessment or additional visits.
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Controled Trial
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Obstructive sleep apnea; Obesity; Weight loss program; Exercise; CPAP treatment