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

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.