Weight-loss Treatment Through Smartphone-assisted Dietary Coaching

Recruitment process will be conducted in two parts. During the first part potential participants will be recruited:

• At the obesity centre during the current obesity consultation
• During regularly information events at the obesity centre flyers will be handed out.
• During training courses for general practitioner at the obesity centre flyers will be handed out.
• Through the network Medical AdiNetwork flyers will be send to general practitioner.
• Advertisement: via website Oviva, Berne University of Applied Science, Zentrum für Adipositas- und Stoffwechselmedizin Winterthur (ZAS) GmbH; Newspaper "Winterthur Stadt Anzeiger".

Participants receive written and verbal information about the study. After participants have given informed consent for participation the second phase (screening process) take place. The researchers determine eligibility of participants based on the inclusion and exclusion criteria at the Zentrum für Adipositas- und Stoffwechselmedizin Winterthur GmbH.

Description of variables:

Weight: Measurement take place in the morning, using a clinically validated and calibrated scale (Seca mBCA 515, medical Body Composition Analyzer). The participant should be clothed lightly, without shoes. Weight is recorded within 0.01 kg.

BMI is calculated by dividing body weight (in kilograms) by height (in meters)2 Height is measured using a calibrated stadiometer (Forma Seca). The subject stands erect with feet positioned on the floor board of the stadiometer. Heels, buttocks, and back of head touch the back board of the stadiometer with arms by sides.

Waist circumference: For the measurement the tape will be located midway between the lower rib and iliac crest. Each measurement is performed twice and recorded within 0.5 cm. If the difference between the measurements is greater than 1 cm, a third measurement will be performed, and the mean of the two closest measurements will be calculated. The participant stand with feet close together, wear little clothing, should be relaxed, and the measurements should be taken at the end of a normal expiration.

Body fat will be measured by Bioelectrical impedance analysis (Seca mBCA 515, medical Body Composition Analyzer). Participants will be asked not to eat, not to drink, not to smoke and not to do any sport 1h before BIA measurement. They were also asked not to consume caffeine or alcohol and other drugs 24 hours before. Bladder should be emptied before measurement. Participants are lightly dressed during measurement and wear no tights. Measurement while Standing.

Laboratory parameters: Subjects have to be fasting over night (8 hours), abstained from smoking, alcohol ingestion, caffeine-containing beverages, and vigorous exercise 48 h before the experiments. The investigators inserted one venous catheter in a large antecubital vein for blood sampling at week 0, 12 and 52.

Blood glucose: filling in a small fluoride containing tube to put aside in the refrigerator at 5°C. Standard value: < 5.6 mmol/l.

HbA1c: filling in a small EDTA containing tube to put aside in the refrigerator at 5°C. Standard value: <5.6%.

Triglyceride: filling in a special tube for centrifugation (10 min at 6000 rpm) for extraction of blood serum to put aside in the refrigerator at 5°C. Standard value: < 2.26 mmol/l.

Insulin: filling in a special tube for centrifugation (10 min at 6000 rpm) for extraction of blood serum to put aside in the refrigerator at 5°C. Standard value: 2.6-24.9 mIU/l.

HDL-Cholesterol: filling in a special tube for centrifugation (10 min at 6000 rpm) for extraction of blood serum to put aside in the refrigerator at 5°C. Standard value: > 1.69 mmol/l (no cardiovascular risk); 1.15-1.68 mmol/l (moderate cardiovascular risk); < 1.14 mmol/l (high cardiovascular risk)

Beta-HCG filling in serum tube with seperating gel. Standard value: <5 U/I.

Vital signs: Blood pressure and heart rate will be investigated by the method of Riva Rocci with a special measuring instrument (Firma boso-medicus SN 768 00 440 729 Bosch+Sohn GmbH und Co) and a stethoscope. The patient has to be sit down for more then 15 min. These measurements will be carried out 3 times in a row and the mean value will be used.

Statistical Analysis

The following statistical hypotheses will be tested for the primary outcome:

Null hypothesis: Change in weight from baseline to week 52 = 0 Alternative hypothesis: Change in weight from baseline to week 52 ≠ 0 The sample size calculation was based on the statistical hypotheses. Using a two-sided Wilcoxon signed-rank test with significance level 0.05 and power 80%, a sample size of 36 is needed to detect a weight change from baseline to week 52 of 0.5 standard deviation, which corresponds to a medium effect size according to Cohen. To account for drop-outs 50 patients will be enrolled in the study

The following analysis populations will be used:

• Intention-to-treat (ITT) Population.
• Per protocol (PP) Population.

The primary outcome will be analyzed based on the ITT population. A supportive analysis based on the PP population will be performed. For the primary outcome, the change in weight will be calculated from baseline to week 52. The null hypothesis will be tested using a two-sided Wilcoxon signed-rank test with significance level 0.05. All outcomes will be analyzed based on the ITT population. Supportive analyses based on the PP population will be performed. For all secondary outcomes the changes will be calculated from baseline to the specified time points. The changes over the whole observation period will be investigated using non-parametric ANOVA methods for longitudinal data. Post-hoc tests for changes at all measured time points may be performed using Wilcoxon signed-rank tests. Correlations between outcome variables will be investigated using Spearman's rank correlation coefficient. Two-tailed tests with significance level 0.05 will be used for all analyses. No adjustment for multiple testing will be performed. All outcome variables will be summarized using descriptive statistics. All analyses will be performed using the latest version of R (http://www.r-project.org).

No imputation of missing data will be performed. A row denoted "Missing" will be included in count tabulations if necessary to account for drop-outs and missing values. For continuous variables a column with the number of available observations will be added. Patients lost to follow-up before reaching the primary outcome will not be replaced. The expected drop-out rate has been accounted for in the sample size calculation.

Data Management

• for smartphone assisted coaching: Data entry by users (both the patient and the dietitian) are always validated used predefined patterns and range checks. If for any reason something goes wrong the user is informed about the unsuccessful data entry and might be (depending on the severity of the error) forced to login to the respective system again to assert that no inconsistent state is displayed to the user. Data is kept consistent by validity checks defined by dietitians and is stored in a highly structured and consistency-constrained database hosted by a medical infrastructure provider.
• On-site clinical data management: All data are acquired by 2 persons (study nurse and clinical subinvestigator) and are electronically immigrated from different equipment in our electronically database. Data can than extracted for CRF and data analysis. The patient key list will be archived at the clinic site, only the PI has the insight.
• All electronic data will be transferred via secure connections and stored in a secure facility, according to regulations for sensitive private information.

Adverse or serious adverse events are not expected in this kind of intervention. But if happen, these events will be described in the CRF, because they may be happened non-causal.

Quality assurance: All study personnel will be instructed by the PI for all study procedures. The PI will furthermore ensure on-going correct data collection at the obesity center and the Sponsor will ensure Oviva technical functionality and coaching operations. All study data will be archived for a minimum of 10 years after study termination or premature termination of the clinical trial.

Follow standardized procedures and in accordance with the provisions blood samples are generally stored at 5 degree celsius. Default storage: Blood samples (EDTA) for seven days; Blood serum for one year. Afterwards, blood samples are destroyed.

If the subject withdraws consent, the blood samples will be analyzed and afterwards destroyed immediately. Data will be analyzed and anonymised.

Monitoring: The monitor will visit the PI and study centre at periodic intervals, in addition to maintaining necessary telephonic and written communication. The monitor will maintain current personal knowledge of the study through observation, review of study records and source documentation and discussion of the conduct of the study with the PI and their study team.

• An initiation visit will be performed before starting recruitment to ensure that the site personnel have been thoroughly trained and the site is provided with all clinical trial supplies.
• The first monitoring visit will be conducted in March 2016 shortly after the first participant has been enrolled to ensure that criteria for inclusion and exclusion have been met and that all protocol procedures are being followed appropriately. All patients enrolled will be verified to have met all inclusion criteria.
• Subsequent monitoring visits: Study Site will be monitored approximately 3 times depending on the demands of the study (week 12, week 52, and week 104).
• Closure of Study: A Site Close-Out Visit will be conducted after all participants have completed the study and all queries have been answered. At this visit the monitors will ensure that all trial documentation is in place, and will discuss archiving procedures with the site.
• Communication between visits: Between monitoring visits, investigators will be telephoned regularly by the monitors to verify patient enrolment status, review study progress, answer protocol questions, CRF completion status and queries, and to ensure that the study proceeds in a timely manner.

Change Management: Basically, study will be conducted in compliance with the study protocol. If deviations are necessary, like changes to eligibility criteria, study design, recruitment, assessment, intervention, outcomes, analyses) the proposed amendment will be submitted well-founded to the sponsor. All investigators can make written suggestions in this regard after consulting principal investigator. A written consent will be obtained from the sponsor.

Substantial amendments are only implemented after approval of the CEC. Under emergency circumstances, deviations from the protocol to protect the rights, safety and well-being of human subjects may proceed without prior approval of the sponsor and the CEC. Such deviations will be documented and reported to the sponsor and the CEC as soon as possible.

All Non-substantial amendments are communicated to the CEC within the Annual Safety Report (ASR). Changes in the protocol are performed by the PI. The written correspondence is kept in the Investigator Site File.