<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03791242</url>
  </required_header>
  <id_info>
    <org_study_id>0199138/2018</org_study_id>
    <nct_id>NCT03791242</nct_id>
  </id_info>
  <brief_title>Ketogenic Diet and CPAP Previous Bariatric Surgery</brief_title>
  <official_title>A Prospective, Randomized, Multi-center Comparative Effectiveness Study of Apnea-Hypopnea Index Using CPAP or CPAP Plus Ketogenic Diet for Treatment of Obstructive Sleep Apnea in Patients Scheduled for Bariatric Surgery</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Roma La Sapienza</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Roma La Sapienza</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Obstructive Sleep Apnea Syndrome (OSAS) and obesity tend to coexist and are often associated&#xD;
      with arterial hypertension, dyslipidaemia, and insulin resistance [1]. Polysomnography (PSG)&#xD;
      is the standard technique for diagnosing OSAS and determining its severity [2]. The results&#xD;
      of the examination provide the Apnea-Hypopnea Index [AHI], or the Respiratory Disturbance&#xD;
      Index [RDI]), which will be used to quantify apnea and classify its severity based on an&#xD;
      international score. In general, an AHI scoring less than 5 is considered &quot;normal&quot; (5-15 mild&#xD;
      sleep apnea; &gt;15 moderate sleep apnea; ≥30 severe sleep apnea).&#xD;
&#xD;
      In order to improve those parameters in obese patients who have been diagnosed with OSAS and&#xD;
      are candidates for BS (BS), national and international guidelines recommend preoperative CPAP&#xD;
      (Continuous Positive Airway Pressure) treatment in order to reduce anaesthesia risks [3-6].&#xD;
      Furthermore, several studies report that obese OSAS patients benefit from preoperative weight&#xD;
      loss [1,7] (in terms of AHI index, night snoring and arterial hypertension).&#xD;
&#xD;
      Obese patients who are candidates for BS often go on a preoperative diet in order to decrease&#xD;
      weight and liver volume (especially of the left lobe) and correct any vitamin/mineral&#xD;
      deficiency. The results of a recently published study show that 4 weeks of Ketogenic&#xD;
      Micronutrient Enriched Diet (KMED) significantly reduce body weight, liver lobe volume and&#xD;
      vitamin/mineral deficiencies in obese patients who prepare to undergo BS [8], with resulting&#xD;
      foreseeable reduction of intraoperative complications and surgical time.&#xD;
&#xD;
      To date, there are no prospective multicenter randomized trials demonstrating whether a&#xD;
      preoperative ketogenic diet associated with CPAP use improves OSAS versus treatment with CPAP&#xD;
      alone, with the possibility of reducing the preoperative treatment period.&#xD;
&#xD;
      Aim of the study: To assess the clinical advantage in combining two preoperative strategies&#xD;
      (CPAP + KMED) compared to preoperative treatment with CPAP alone, for the reduction of&#xD;
      surgical risks in morbidly obese patients with severe OSAS who are scheduled for BS.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A recent clinical study published in 2014 on the New England Journal of Medicine found that&#xD;
      often even an initial modest body weight reduction can favourably modify apnea events and&#xD;
      severity during the night, with the latter that can be reduced by about 30% (AHI) for a 10%&#xD;
      weight reduction compared to the initial weight [1]. However, considering the average AHI&#xD;
      data reported by the authors, which do not include post-treatment information, statistical&#xD;
      elements at our disposal are insufficient to assess the &quot;effect size&quot;. Therefore, a sample of&#xD;
      65 patients per group will be needed for the evaluation of the primary endpoint (statistical&#xD;
      significance of 5% [two-tailed], 80% power, &quot;effect size&quot; 0.25, calculated using the G* Power&#xD;
      software, Düsseldorf, Germany). A total of 66 patients will be enrolled (22 patients per&#xD;
      participating site) on the baseline assumption of a dropout of 10%. Most drop-outs may result&#xD;
      from CPAP use and, in particular, discomfort experienced by the patient with tube and facial&#xD;
      mask, difficult acceptance because of psychological reasons (shame or negative expectations&#xD;
      in terms of partner judgment), or subjective feeling of claustrophobic suffocation or&#xD;
      anxiety. The expected drop-out for KMED with the Ketocompleat protocol is 15%. Indeed, in&#xD;
      Schiavo et al [8] study, most patients (86%) showed high acceptability of the Ketocompleat&#xD;
      ketogenic protocol prescribed in the four weeks of preoperative treatment, and the only side&#xD;
      effect reported was mild headache with associated modest halitosis, especially during the&#xD;
      initial treatment days, which, however, did not prevent patients from continuing with the&#xD;
      protocol.&#xD;
&#xD;
      Experiment design and patient randomization&#xD;
&#xD;
      Spontaneous, prospective, comparative and multicentre trial including 66 patients with severe&#xD;
      OSAS (polysomnogram with AHI≥30) suitable for gastric bypass surgery, and randomized into 2&#xD;
      groups:&#xD;
&#xD;
      GROUP 1: 33 morbidly obese patients with severe OSAS and suitable for gastric bypass surgery,&#xD;
      who underwent 4 weeks of CPAC treatment (these patients will not be required to change their&#xD;
      eating habits) according to the standard; GROUP 2: 33 morbidly obese patients with severe&#xD;
      OSAS and BS candidates who underwent CPAC + KMED treatment for 4 weeks.&#xD;
&#xD;
      Randomization will be conducted via permuted-block design (PBD), with stratification of&#xD;
      patients based on age, gender, and enrollement site Preoperative ketogenic&#xD;
      micronutrient-enriched diet: The ketogenic diet has been used for many years in clinical&#xD;
      settings [9]. Given its safety and effectiveness in determining weight loss, associated with&#xD;
      optimal adherence and patient compliance, the ketogenic diet has recently been used by&#xD;
      several obesity surgery centers in the preoperative management of obese patients who are&#xD;
      candidates for BS [8, 10-11]. The validated Ketocompleat protocol [8] will serve as the KMED&#xD;
      of choice. In particular, the protocol will provide a diet with ketogenic characteristics&#xD;
      that patients will have to follow for breakfast, snack, lunch and snack, and replacement of&#xD;
      the evening meal with the Ketocompleat ketogenic supplement. Figure 1 shows a daily diet&#xD;
      sample.&#xD;
&#xD;
      In short, to ensure that all patients follow the same diet, the investigator will use the&#xD;
      software (https://www.eatthismuch.com) to develop two ketogenic diet plans (plan 1, days&#xD;
      1-14; plan 2, days 15-28), containing specific amounts of foods to be consumed. Each&#xD;
      ketogenic plan will comprise: 1150 to 1250 kcal/day, of which 4% carbohydrates, 71% fat, and&#xD;
      25% proteins. The composition of the supplement to use for the trial (Ketocompleat, MVMedical&#xD;
      Solutions, Serravalle, Republic of San Marino) is shown in Table 1. Ketocompleat is a&#xD;
      supplement included in the Ministry of Health's food supplement register (code 94721); given&#xD;
      its carbohydrate-free formulation, it can easily be associated to a low-carbohydrate&#xD;
      ketogenic diet. The diet plans and the Ketocompleat supplement will be provided free of&#xD;
      charge to all trial participants by MVMedical Solutions, which will have no role in designing&#xD;
      trial and patient enrollement in the different participating sites, or in processing any&#xD;
      trial-related data.&#xD;
&#xD;
      Patient adherence to the prescribed preoperative diet will be confirmed through the following&#xD;
      scientifically validated tests: 3-Day Estimated Food and Records and 72-h Recalls [8], while&#xD;
      the presence of ketone bodies in the urine (Ketur-Test, Roche Diagnostic, Milan, Italy)&#xD;
      associated with weight loss will be used as the patient compliance index. The Ketur test will&#xD;
      be performed in outpatient mode during the weekly diet check.&#xD;
&#xD;
      Polysomnography&#xD;
&#xD;
      Polysomnography is a sleep study that collects a variety of parameters and conditions, such&#xD;
      as oxygen saturation, heart rate, presence (or absence in the case of apnea) of airflow&#xD;
      through mouth and nose, presence (or absence) of thoracic and abdominal movements, position&#xD;
      held by the subject during sleep, and snoring during sleep. By analysing these data, it will&#xD;
      be possible to define: number of episodes of haemoglobin desaturation during sleep&#xD;
      (desaturation index per hour - ODIindex), presence or absence of apnea during sleep,&#xD;
      differentiating between true apnea true (absence of air flow) and hypopneas (air flow&#xD;
      present, though substantially reduced), determination of &quot;obstructive&quot; &quot;central&quot; or &quot;mixed&quot;&#xD;
      apnea/hypopnea, hourly frequency of apnea/ hypopnea ( apnea/hypopnea events per hour or AHI&#xD;
      index), which allows defining the degree of severity of the disorder (disease stage), AHI in&#xD;
      supine and non-supine position (often this datum documents greater apnea frequency in the&#xD;
      supine position compared to data relating to the patient in lateral decubitus), and snoring&#xD;
      time during sleep. In order to evaluate the clinical advantage offered by the combination of&#xD;
      the two preoperative strategies (CPAP and ketogenic diet therapy) compared to CPAP&#xD;
      preoperative treatment alone, for the reduction of the surgical risk in morbidly obese OSAS&#xD;
      BS candidates, patients of both groups will undergo polysomnography before the trial and&#xD;
      after 4 weeks of CPAP alone or combined CPAP + KMED treatment. The tolerance interval for PSG&#xD;
      execution at the end of the treatment is 7 days; otherwise, patients will be considered&#xD;
      drop-outs.&#xD;
&#xD;
      CPAP-type ventilator prescription CPAP use is the gold standard for the treatment of sleep&#xD;
      apnea syndrome. The CPAP device consists of a small fan connected to the patient through a&#xD;
      tube and a facial mask (nasal or oronasal). This device provides continuous air flow that&#xD;
      maintains the airways open, preventing the collapse (closing) of the critical points&#xD;
      responsible for respiratory obstruction during sleep, thus avoiding or limiting sleep apnea.&#xD;
      Patients with severe OSAS who are BS candidates will be treated with CPAP only at night&#xD;
      (Group 1), or CPAP at night + KMED daily (Group 2), for 4 weeks.&#xD;
&#xD;
      Preoperative investigations and after 4 weeks of CPAP or CPAP + KMED treatment&#xD;
&#xD;
      In the BS Centers participating in the trial, both experimental groups will undergo the&#xD;
      following evaluation:&#xD;
&#xD;
        -  Complete blood count with WBC differential, triglycerides, total cholesterol, HDL&#xD;
           cholesterol, LDL cholesterol, triglycerides, GOT, GPT, ΥGT, nitrogen, creatinine, urea,&#xD;
           iron, ferritin, ketone bodies, baseline glucose, baseline insulin, and CRP&#xD;
&#xD;
        -  Body weight, height and BMI calculation&#xD;
&#xD;
        -  Waist and hip circumference&#xD;
&#xD;
        -  Chest X-ray&#xD;
&#xD;
        -  Blood gas analysis&#xD;
&#xD;
        -  Spirometry&#xD;
&#xD;
        -  Polysomnography&#xD;
&#xD;
      Laboratory/instrumental clinical analyses, polysomnography and CPAP will be performed in the&#xD;
      sites participating in the project; data obtained will be evaluated by a Pneumologist, while&#xD;
      the statistical analysis will be entrusted to a Biostatistician.&#xD;
&#xD;
      Inclusion criteria: patients of both sexes with BMI ≥35 with severe OSAS; age between 18-65&#xD;
      years; non-smokers or who have quit smoking for at least 3 months.&#xD;
&#xD;
      Exclusion criteria: kidney and/or liver conditions that would make a KMED diet unsuitable&#xD;
      (creatinine levels &gt;1.8 mg/dL or liver enzyme levels (glutamic pyruvic transaminase [GPT] or&#xD;
      glutamic oxaloacetic transaminase [GOT]) less than three times over the upper normal&#xD;
      threshold, and psychological problems that would make CPAP treatment problematic. Patients&#xD;
      with obesity &gt;60 BMI.&#xD;
&#xD;
      Primary endpoint: evaluate the effect of combined (CPAP + KMED) therapy vs CPAP on the AHI&#xD;
      after 4 weeks. Secondary end points: evaluate CRP levels, arterial pressure and lipid panel&#xD;
      (total cholesterol, HDL, LDL and triglycerides) in the two study groups.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 21, 2019</start_date>
  <completion_date type="Actual">May 19, 2021</completion_date>
  <primary_completion_date type="Actual">March 19, 2021</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Single (Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Apnea Hypopnea Index</measure>
    <time_frame>0 - 4 weeks</time_frame>
    <description>evaluate the effect of combined (CPAP + KMED) therapy vs CPAP on the AHI after 4 weeks</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Blood exam</measure>
    <time_frame>0 - 4 weeks</time_frame>
    <description>C-reactive protein</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Arterial Pressure</measure>
    <time_frame>0 - 4 weeks</time_frame>
    <description>arterial pressure measure</description>
  </other_outcome>
  <other_outcome>
    <measure>Blood exam</measure>
    <time_frame>0 - 4 weeks</time_frame>
    <description>Lipid pattern</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">66</enrollment>
  <condition>Obstructed Sleep Apnea Syndrome in Patient Candidate to Baratric Surgery</condition>
  <arm_group>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>33 morbidly obese patients with severe OSAS and suitable for gastric bypass surgery, who underwent 4 weeks of CPAC treatment (these patients will not be required to change their eating habits) according to the standard</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>33 morbidly obese patients with severe OSAS and BS candidates who underwent CPAC + KMED treatment for 4 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Cpap and ketogenic diet</intervention_name>
    <description>Patients with severe OSAS who are BS candidates will be treated with CPAP only at night (Group 1), or CPAP at night + KMED daily (Group 2), for 4 weeks</description>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_label>Group 2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  BMI ≥35 Kg/m2&#xD;
&#xD;
          -  Severe OSAS&#xD;
&#xD;
          -  Non-smokers or who have quit smoking for at least 3 months&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  kidney and/or liver conditions that would make a KMED diet unsuitable (creatinine&#xD;
             levels &gt;1.8 mg/dL or liver enzyme levels (glutamic pyruvic transaminase [GPT] or&#xD;
             glutamic oxaloacetic transaminase [GOT]) less than three times over the upper normal&#xD;
             threshold&#xD;
&#xD;
          -  psychological problems that would make CPAP treatment problematic&#xD;
&#xD;
          -  BMI &gt; 60 Kg/m2&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>ICOT Hospital</name>
      <address>
        <city>Latina</city>
        <zip>04100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>June 2021</verification_date>
  <study_first_submitted>December 28, 2018</study_first_submitted>
  <study_first_submitted_qc>December 28, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">January 2, 2019</study_first_posted>
  <last_update_submitted>June 22, 2021</last_update_submitted>
  <last_update_submitted_qc>June 22, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 25, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Roma La Sapienza</investigator_affiliation>
    <investigator_full_name>Gianfranco Silecchia</investigator_full_name>
    <investigator_title>MD PhD Prof. G. Silecchia</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sleep Apnea Syndromes</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03791242
org study id: 0199138/2018
nct id: NCT03791242
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Obstructive Sleep Apnea Syndrome (OSAS) and obesity tend to coexist and are often associated
      with arterial hypertension, dyslipidaemia, and insulin resistance [1]. Polysomnography (PSG)
      is the standard technique for diagnosing OSAS and determining its severity [2]. The results
      of the examination provide the Apnea-Hypopnea Index [AHI], or the Respiratory Disturbance
      Index [RDI]), which will be used to quantify apnea and classify its severity based on an
      international score. In general, an AHI scoring less than 5 is considered "normal" (5-15 mild
      sleep apnea; >15 moderate sleep apnea; ≥30 severe sleep apnea).

      In order to improve those parameters in obese patients who have been diagnosed with OSAS and
      are candidates for BS (BS), national and international guidelines recommend preoperative CPAP
      (Continuous Positive Airway Pressure) treatment in order to reduce anaesthesia risks [3-6].
      Furthermore, several studies report that obese OSAS patients benefit from preoperative weight
      loss [1,7] (in terms of AHI index, night snoring and arterial hypertension).

      Obese patients who are candidates for BS often go on a preoperative diet in order to decrease
      weight and liver volume (especially of the left lobe) and correct any vitamin/mineral
      deficiency. The results of a recently published study show that 4 weeks of Ketogenic
      Micronutrient Enriched Diet (KMED) significantly reduce body weight, liver lobe volume and
      vitamin/mineral deficiencies in obese patients who prepare to undergo BS [8], with resulting
      foreseeable reduction of intraoperative complications and surgical time.

      To date, there are no prospective multicenter randomized trials demonstrating whether a
      preoperative ketogenic diet associated with CPAP use improves OSAS versus treatment with CPAP
      alone, with the possibility of reducing the preoperative treatment period.

      Aim of the study: To assess the clinical advantage in combining two preoperative strategies
      (CPAP + KMED) compared to preoperative treatment with CPAP alone, for the reduction of
      surgical risks in morbidly obese patients with severe OSAS who are scheduled for BS.
A recent clinical study published in 2014 on the New England Journal of Medicine found that
      often even an initial modest body weight reduction can favourably modify apnea events and
      severity during the night, with the latter that can be reduced by about 30% (AHI) for a 10%
      weight reduction compared to the initial weight [1]. However, considering the average AHI
      data reported by the authors, which do not include post-treatment information, statistical
      elements at our disposal are insufficient to assess the "effect size". Therefore, a sample of
      65 patients per group will be needed for the evaluation of the primary endpoint (statistical
      significance of 5% [two-tailed], 80% power, "effect size" 0.25, calculated using the G* Power
      software, Düsseldorf, Germany). A total of 66 patients will be enrolled (22 patients per
      participating site) on the baseline assumption of a dropout of 10%. Most drop-outs may result
      from CPAP use and, in particular, discomfort experienced by the patient with tube and facial
      mask, difficult acceptance because of psychological reasons (shame or negative expectations
      in terms of partner judgment), or subjective feeling of claustrophobic suffocation or
      anxiety. The expected drop-out for KMED with the Ketocompleat protocol is 15%. Indeed, in
      Schiavo et al [8] study, most patients (86%) showed high acceptability of the Ketocompleat
      ketogenic protocol prescribed in the four weeks of preoperative treatment, and the only side
      effect reported was mild headache with associated modest halitosis, especially during the
      initial treatment days, which, however, did not prevent patients from continuing with the
      protocol.

      Experiment design and patient randomization

      Spontaneous, prospective, comparative and multicentre trial including 66 patients with severe
      OSAS (polysomnogram with AHI≥30) suitable for gastric bypass surgery, and randomized into 2
      groups:

      GROUP 1: 33 morbidly obese patients with severe OSAS and suitable for gastric bypass surgery,
      who underwent 4 weeks of CPAC treatment (these patients will not be required to change their
      eating habits) according to the standard; GROUP 2: 33 morbidly obese patients with severe
      OSAS and BS candidates who underwent CPAC + KMED treatment for 4 weeks.

      Randomization will be conducted via permuted-block design (PBD), with stratification of
      patients based on age, gender, and enrollement site Preoperative ketogenic
      micronutrient-enriched diet: The ketogenic diet has been used for many years in clinical
      settings [9]. Given its safety and effectiveness in determining weight loss, associated with
      optimal adherence and patient compliance, the ketogenic diet has recently been used by
      several obesity surgery centers in the preoperative management of obese patients who are
      candidates for BS [8, 10-11]. The validated Ketocompleat protocol [8] will serve as the KMED
      of choice. In particular, the protocol will provide a diet with ketogenic characteristics
      that patients will have to follow for breakfast, snack, lunch and snack, and replacement of
      the evening meal with the Ketocompleat ketogenic supplement. Figure 1 shows a daily diet
      sample.

      In short, to ensure that all patients follow the same diet, the investigator will use the
      software (https://www.eatthismuch.com) to develop two ketogenic diet plans (plan 1, days
      1-14; plan 2, days 15-28), containing specific amounts of foods to be consumed. Each
      ketogenic plan will comprise: 1150 to 1250 kcal/day, of which 4% carbohydrates, 71% fat, and
      25% proteins. The composition of the supplement to use for the trial (Ketocompleat, MVMedical
      Solutions, Serravalle, Republic of San Marino) is shown in Table 1. Ketocompleat is a
      supplement included in the Ministry of Health's food supplement register (code 94721); given
      its carbohydrate-free formulation, it can easily be associated to a low-carbohydrate
      ketogenic diet. The diet plans and the Ketocompleat supplement will be provided free of
      charge to all trial participants by MVMedical Solutions, which will have no role in designing
      trial and patient enrollement in the different participating sites, or in processing any
      trial-related data.

      Patient adherence to the prescribed preoperative diet will be confirmed through the following
      scientifically validated tests: 3-Day Estimated Food and Records and 72-h Recalls [8], while
      the presence of ketone bodies in the urine (Ketur-Test, Roche Diagnostic, Milan, Italy)
      associated with weight loss will be used as the patient compliance index. The Ketur test will
      be performed in outpatient mode during the weekly diet check.

      Polysomnography

      Polysomnography is a sleep study that collects a variety of parameters and conditions, such
      as oxygen saturation, heart rate, presence (or absence in the case of apnea) of airflow
      through mouth and nose, presence (or absence) of thoracic and abdominal movements, position
      held by the subject during sleep, and snoring during sleep. By analysing these data, it will
      be possible to define: number of episodes of haemoglobin desaturation during sleep
      (desaturation index per hour - ODIindex), presence or absence of apnea during sleep,
      differentiating between true apnea true (absence of air flow) and hypopneas (air flow
      present, though substantially reduced), determination of "obstructive" "central" or "mixed"
      apnea/hypopnea, hourly frequency of apnea/ hypopnea ( apnea/hypopnea events per hour or AHI
      index), which allows defining the degree of severity of the disorder (disease stage), AHI in
      supine and non-supine position (often this datum documents greater apnea frequency in the
      supine position compared to data relating to the patient in lateral decubitus), and snoring
      time during sleep. In order to evaluate the clinical advantage offered by the combination of
      the two preoperative strategies (CPAP and ketogenic diet therapy) compared to CPAP
      preoperative treatment alone, for the reduction of the surgical risk in morbidly obese OSAS
      BS candidates, patients of both groups will undergo polysomnography before the trial and
      after 4 weeks of CPAP alone or combined CPAP + KMED treatment. The tolerance interval for PSG
      execution at the end of the treatment is 7 days; otherwise, patients will be considered
      drop-outs.

      CPAP-type ventilator prescription CPAP use is the gold standard for the treatment of sleep
      apnea syndrome. The CPAP device consists of a small fan connected to the patient through a
      tube and a facial mask (nasal or oronasal). This device provides continuous air flow that
      maintains the airways open, preventing the collapse (closing) of the critical points
      responsible for respiratory obstruction during sleep, thus avoiding or limiting sleep apnea.
      Patients with severe OSAS who are BS candidates will be treated with CPAP only at night
      (Group 1), or CPAP at night + KMED daily (Group 2), for 4 weeks.

      Preoperative investigations and after 4 weeks of CPAP or CPAP + KMED treatment

      In the BS Centers participating in the trial, both experimental groups will undergo the
      following evaluation:

        -  Complete blood count with WBC differential, triglycerides, total cholesterol, HDL
           cholesterol, LDL cholesterol, triglycerides, GOT, GPT, ΥGT, nitrogen, creatinine, urea,
           iron, ferritin, ketone bodies, baseline glucose, baseline insulin, and CRP

        -  Body weight, height and BMI calculation

        -  Waist and hip circumference

        -  Chest X-ray

        -  Blood gas analysis

        -  Spirometry

        -  Polysomnography

      Laboratory/instrumental clinical analyses, polysomnography and CPAP will be performed in the
      sites participating in the project; data obtained will be evaluated by a Pneumologist, while
      the statistical analysis will be entrusted to a Biostatistician.

      Inclusion criteria: patients of both sexes with BMI ≥35 with severe OSAS; age between 18-65
      years; non-smokers or who have quit smoking for at least 3 months.

      Exclusion criteria: kidney and/or liver conditions that would make a KMED diet unsuitable
      (creatinine levels >1.8 mg/dL or liver enzyme levels (glutamic pyruvic transaminase [GPT] or
      glutamic oxaloacetic transaminase [GOT]) less than three times over the upper normal
      threshold, and psychological problems that would make CPAP treatment problematic. Patients
      with obesity >60 BMI.

      Primary endpoint: evaluate the effect of combined (CPAP + KMED) therapy vs CPAP on the AHI
      after 4 weeks. Secondary end points: evaluate CRP levels, arterial pressure and lipid panel
      (total cholesterol, HDL, LDL and triglycerides) in the two study groups.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Single (Investigator)
measure: Apnea Hypopnea Index
time frame: 0 - 4 weeks
description: evaluate the effect of combined (CPAP + KMED) therapy vs CPAP on the AHI after 4 weeks
measure: Blood exam
time frame: 0 - 4 weeks
description: C-reactive protein
measure: Arterial Pressure
time frame: 0 - 4 weeks
description: arterial pressure measure
measure: Blood exam
time frame: 0 - 4 weeks
description: Lipid pattern
arm group label: Group 1
arm group type: Active Comparator
description: 33 morbidly obese patients with severe OSAS and suitable for gastric bypass surgery, who underwent 4 weeks of CPAC treatment (these patients will not be required to change their eating habits) according to the standard
arm group label: Group 2
arm group type: Active Comparator
description: 33 morbidly obese patients with severe OSAS and BS candidates who underwent CPAC + KMED treatment for 4 weeks
intervention type: Device
intervention name: Cpap and ketogenic diet
description: Patients with severe OSAS who are BS candidates will be treated with CPAP only at night (Group 1), or CPAP at night + KMED daily (Group 2), for 4 weeks
arm group label: Group 1
arm group label: Group 2
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
facility: 
country: Italy
responsible party type: Principal Investigator
investigator affiliation: University of Roma La Sapienza
investigator full name: Gianfranco Silecchia
investigator title: MD PhD Prof. G. Silecchia
mesh term: Sleep Apnea Syndromes
sharing ipd: Undecided