<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/NCT03788915</url>
  </required_header>
  <id_info>
    <org_study_id>LIVA USouthernDenmark</org_study_id>
    <nct_id>NCT03788915</nct_id>
  </id_info>
  <brief_title>Weight Loss and Reversing T2D Through eHealth Coaching</brief_title>
  <acronym>LIVA</acronym>
  <official_title>Facilitating Weight Loss and Reversing Type 2 Diabetes (T2D) by Means of a Collaborative eHealth Lifestyle Coaching Intervention in Primary Care - A 2-year Randomised Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Southern Denmark</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Odense University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Southern Denmark</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>
      Background: Systematic reviews conclude that Internet and mobile interventions can&#xD;
      significantly change lifestyle in a short time span. The applicant has developed a&#xD;
      collaborative eHealth tool (LIVA) that has led to a significant and clinically relevant&#xD;
      weight loss of 5.4 to 7.0 kg over 12 to 20 months in primary care settings. The objective of&#xD;
      this study is to develop and evaluate a model targeting long-term effects using eHealth&#xD;
      coaching assisted by machine learning-generated advice intervention for overweight patients&#xD;
      at risk of developing diabetes as well as current type 2 diabetes (T2D) patients in a primary&#xD;
      care setting.&#xD;
&#xD;
      Methods and analysis: Randomized controlled trial with 1-year intervention and 1-year&#xD;
      maintenance. The primary outcome is weight loss and the secondary outcome is reduced HbA1c&#xD;
      level. The study will comprise 340 overweight patients of which 170 will have T2D. Individual&#xD;
      data will be obtained from clinical measurements, questionnaire data, registered from the&#xD;
      collaborative eHealth tool, as well as other registry data at baseline and at 6, 12 and 24&#xD;
      months. The core of the intervention is the establishment of an empathic relationship and&#xD;
      ongoing real-life coaching using the LIVA app (working together with native iOS and Android)&#xD;
      and Internet for patients combined with an effective coaching module supported by machine&#xD;
      learning methods. The intervention will be compared with usual care.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      1. Introduction With diseases such as Type 2 diabetes (T2D), adiposity and cardiovascular&#xD;
           diseases rapidly increasing, cost effective management is needed (World Health&#xD;
           Organization, 2017). Lifestyle improvements such as weight loss, diet and exercise&#xD;
           managed in a primary care setting has shown significant impact on reduced risk of&#xD;
           cardiovascular disease and reversing T2D for 46-56% of patients with T2D (Lean et al.,&#xD;
           2017, Johansen et al., 2017). Based on these findings, weight loss among overweight&#xD;
           patients with T2D and patients at risk of developing T2D has important clinical and&#xD;
           societal effects.&#xD;
&#xD;
           Traditional lifestyle interventions are mostly ineffective and expensive long-term.&#xD;
           Internet and mobile technology-based interventions aiming at promoting healthy&#xD;
           lifestyles have shown potential for scalability, accessibility, and cost effective use&#xD;
           in primary care settings both for overweight patients and T2D patients (Brandt et al,&#xD;
           2011, Haste et al., 2017, Komkova et al 2018). However, there is only sparse knowledge&#xD;
           about whether the beneficial effects are long-term (Afshin et al., 2016, Levine et al.,&#xD;
           2015).&#xD;
&#xD;
           Qualitative research studies comprising patients, general practitioners and the&#xD;
           healthcare professionals' perspectives suggest that the establishment of an empathic&#xD;
           relationship is key to long-term lifestyle change (Brandt et al., 2018a, 2018b and&#xD;
           2018c). An observational study among 103 diabetes patients using the collaborative&#xD;
           eHealth tool (LIVA) demonstrated a clinically significant self-reported weight loss of&#xD;
           4.7 kg among users who had been on the platform for 90+ days (Komkova et al., 2018).&#xD;
           Modelling the association between weight reduction and decreased health care costs, the&#xD;
           same study estimated that the program will save 2,667€ annually for every patient and be&#xD;
           cost effective from a municipal perspective even with only 1 year of implementation data&#xD;
           for T2D patients (Mukherjee et al., 2016, Nichols et al., 2016, Bell et al., 2014).&#xD;
&#xD;
           In the present study, the model to be tested is a lifestyle intervention using a&#xD;
           cost-effective eHealth coaching tool (LIVA) model: following an initial meeting,&#xD;
           frequent digital communication is established between health coach and patient,&#xD;
           supplemented by machine learning. Machine learning is performed using data automatically&#xD;
           gathered from patients' relevant daily lifestyle registrations such as activity level,&#xD;
           step count, diet goals fulfilment, sleep, etc. Data will be analysed to predict&#xD;
           attrition and outcome. The developed algorithms and models will then be used to increase&#xD;
           outcome and decrease dropout by supporting the health coaches with information and&#xD;
           guidance how to deliver better coaching directly and indirectly. This intervention will&#xD;
           be compared with standard lifestyle interventions in a municipality setting.&#xD;
&#xD;
        2. Study objectives and hypothesis The aim of this study is to evaluate the clinical&#xD;
           efficacy of the LIVA intervention for overweight patients at risk of developing a&#xD;
           chronic disease and overweight type 2 diabetes patients in a primary care setting. We&#xD;
           hypothesize that the LIVA intervention will lead to significant weight loss, reduced&#xD;
           HbA1C, and reduced need for medication compared to usual care.&#xD;
&#xD;
        3. Methods and analysis Study design and setting The study is a randomized controlled trial&#xD;
           with one year of intervention and one year of subsequent maintenance, with continued&#xD;
           collection of clinical and questionnaire data, where the primary endpoint is weight loss&#xD;
           and the secondary endpoint is HbA1c. The intervention is conducted in a real life&#xD;
           setting; all data management will be at the Research Unit for General Practice,&#xD;
           Department of Public Health, Primary trial sponsor, J.B. Winsløwsvej 9A, 5000 Odense C,&#xD;
           Denmark. Recruitment of patients to the study is in 8-10 municipalities within the&#xD;
           Region of Southern Denmark and the Capitol Region of Denmark. The study has been&#xD;
           registered at https://register.clinicaltrials.gov. On-boarding of patients began in&#xD;
           March 2018 and the results are expected to be accessible during 2021.&#xD;
&#xD;
           Study population and inclusion criteria Flow of patients is described in figure 1. In&#xD;
           each municipality, advertising through social media will be used to recruit eligible&#xD;
           patients for municipal preventive offers, fulfilling the inclusion criteria in the study&#xD;
           (Table 1). These patients will be contacted by phone and/ or email, and informed about&#xD;
           the study and asked to register if they accept the offer to participate.&#xD;
&#xD;
           Table 1. Inclusion and exclusion criteria&#xD;
&#xD;
           Inclusion criteria:&#xD;
&#xD;
           BMI 45 ≥ 30 kg/m2 Aged 18 -70 years&#xD;
&#xD;
           Exclusion criteria:&#xD;
&#xD;
           Fails to provide informed consent Fails to complete the initial questionnaire or&#xD;
           understand Danish No Internet access in own home through computer or smartphone Is&#xD;
           pregnant or actively trying to get pregnant Experiences mental or serious&#xD;
           life-threatening disease&#xD;
&#xD;
           The 340 eligible patients will be invited to an introduction meeting with an healthcare&#xD;
           professional with a master's in human nutrition or a clinical dietician. This&#xD;
           introductory appointment is scheduled within 7-14 days after the information material is&#xD;
           received by the patient. The patient is weighed and measured according to defined&#xD;
           clinical indicators. Blood indicators are measured through a finger prick blood sample.&#xD;
           The patient is then instructed to use a web link to complete a standard quality of life&#xD;
           questionnaire (SF-12) combined with registration of medication intake and questions&#xD;
           concerning the patient's sociodemographic characteristics, such as educational level,&#xD;
           labour market affiliation, questions concerning work performance, and disease history.&#xD;
&#xD;
           Randomization:&#xD;
&#xD;
           After patients have successfully completed the web questionnaire, they will be&#xD;
           randomized via an automated computer algorithm. This procedure ensures that drop-out&#xD;
           characteristics can be recorded. Patients are randomized in a 60:40 sequencing, where&#xD;
           60% of recruited patients are randomized for the intervention group while the remaining&#xD;
           40% will constitute the control group, based on sample size calculations (Please see&#xD;
           Sample size calculations, below). Randomization is controlled to ensure that 50% of&#xD;
           intervention group and controls will be overweight patients at risk of developing&#xD;
           chronic disease and the other 50% of intervention group and controls will be overweight&#xD;
           diabetes patients.&#xD;
&#xD;
           Intervention:&#xD;
&#xD;
           The intervention is summarised in Table 2. Based on results in the applicant's PhD&#xD;
           thesis, the core of the intervention is the initial establishment of an empathic&#xD;
           relationship with a healthcare professional who is a clinical dietician by profession&#xD;
           and has been working with eHealth lifestyle coaching for more than 2 years (referred to&#xD;
           as the health coach) and who delivers effective remote and/or digital coaching&#xD;
           responsive to the users' own data registrations (Brandt et al, 2018a). Patients in the&#xD;
           intervention group receive a login to the eHealth tool at a personal meeting (either&#xD;
           physical or digital) during which the health coach introduces the program. Together, the&#xD;
           patient and the health coach agree on goals for diet, physical exercise, sleep, etc.&#xD;
           (Brandt et al, 2018b). Using the app, patients fill in a daily record as well as their&#xD;
           comments, concerns and questions for the health coach, who will have access to patient&#xD;
           profiles. The health coach provides individual asynchronous advice according to the&#xD;
           patients' needs based on the patients' own real-time registrations (Brandt et al,&#xD;
           2018c); the health coach's advice is supported by artificial intelligence predictions&#xD;
           using machine learning (Holzinger A. et al, 2017). The coach advises on goal setting&#xD;
           based on the SMART model: Specific, Measurable, Attainable, Relevant, Timely, and&#xD;
           according to a predefined guideline structure (Ryan et al, 2009).&#xD;
&#xD;
           Asynchronous advice will be provided on a weekly basis during the first 6 months.&#xD;
           Subsequently, advice will be given monthly for 6 months. After 12 months, the&#xD;
           participant enters maintenance for 12 months, where the coach will still follow&#xD;
           patients' registrations and may give four to twelve coaching sessions during that year.&#xD;
           Patients can also participate in usual municipally provided preventive medicine&#xD;
           offerings, such as &quot;diabetes school&quot;, to the extent that the municipalities normally&#xD;
           provide such offers.&#xD;
&#xD;
           Conventional care (control group):&#xD;
&#xD;
           Patients randomized to the control group will be offered standard municipal secondary or&#xD;
           tertiary preventive offers.&#xD;
&#xD;
           Study endpoints and assessment:&#xD;
&#xD;
           Measurement of endpoints (weight, HbA1c etc.) will be conducted by the health coach at&#xD;
           baseline and at 6, 12 and 24 months' follow-up.&#xD;
&#xD;
           Primary outcome:&#xD;
&#xD;
           Weight loss from baseline to 12 months' follow-up.&#xD;
&#xD;
           Secondary outcome Reduction in HbA1c for all patients from baseline to 12 months for&#xD;
           patients with T2D.&#xD;
&#xD;
           Other outcomes&#xD;
&#xD;
           The following tertiary outcomes will be measured at baseline and at 12 months:&#xD;
&#xD;
             -  Retention rates among users&#xD;
&#xD;
             -  Patient waist circumference&#xD;
&#xD;
             -  Blood pressure&#xD;
&#xD;
             -  Total cholesterol, LDL, HDL and TG&#xD;
&#xD;
             -  Patients' quality of life&#xD;
&#xD;
             -  Changes in patterns of medication Apart from these outcomes, patient demographic&#xD;
                characteristics (gender, age, highest educational level) will be measured at&#xD;
                baseline.&#xD;
&#xD;
           Analysis strategy Primary analyses will be performed blinded by statisticians and&#xD;
           comprise subgroup analyses based on stratification according to patient characteristics&#xD;
           and experiences. Statistical significance will be inferred at a two-tailed and p&lt;0.05&#xD;
           significance level. All data will be accessible on the Internet in anonymised form to&#xD;
           allow full peer scrutiny and facilitate secondary research.&#xD;
&#xD;
           Sample size calculations The primary objective of this study is measurement of changes&#xD;
           in body weight and waist circumference. Weight loss in the intervention group and&#xD;
           control group will be analysed using appropriate statistical procedures. Based on a&#xD;
           recent study by Haste and colleagues evaluating a web-based weight loss intervention&#xD;
           among men with diabetes, we expect a weight loss of at least 4.5 kg at 12 months in the&#xD;
           intervention group, compared to 2.5 kg in the control group, as well as dropout rates of&#xD;
           39% among the intervention group and 57% among control group at 12 months (Haste et al.,&#xD;
           2017). A power calculation based on the standard deviations observed in the study&#xD;
           performed by Haste et al shows that to detect a difference in weight loss of 2 kg with a&#xD;
           power of 0.95% requires 55 patients in the intervention group and 32 in the control&#xD;
           group. To be able to stratify analyses according to overweight patients at risk of&#xD;
           developing chronic disease and overweight diabetes patients we will therefore recruit&#xD;
           200 (100+100) in the intervention groups and 140 (70+70) controls.&#xD;
&#xD;
        4. Ethics The intervention is not expected to cause any side effects or discomfort except&#xD;
           for the ones a change in lifestyle can bring. The only recognized risk is in relation to&#xD;
           eating disorders (pre-existing or developing during the study) and the dieticians and&#xD;
           nurses involved in the study will specifically look out for indications of this. The&#xD;
           Regional Ethical Committee (Regional Videnskabsetisk Komité) have accepted the study in&#xD;
           according to Danish law. Participant data will be handled and stored in accordance with&#xD;
           rules approved by the Danish Data Inspectorate (Datatilsynet). Permission to handle&#xD;
           individual patient data from the national registries will be obtained from patients and&#xD;
           the Danish Data Inspectorate. All data will be analysed in anonymous form.&#xD;
&#xD;
        5. Publication The results of the studies will be published in international journals in&#xD;
           accordance with the Vancouver rules. Furthermore, participants will be invited to a&#xD;
           presentation of results at the end of the study and news media will be informed.&#xD;
&#xD;
        6. Conflict of Interests Carl J. Brandt has co-founded and works as a medical consultant&#xD;
           for LIVA Healthcare A/S, the company that has developed parts of the technical platform&#xD;
           and will host some of it during the study. Carl J. Brandt works at the Research Unit for&#xD;
           General Practice and CIMT at SDU. Camilla Sortsø is working for LIVA Healthcare A/S,&#xD;
           Jens Søndergaard, Jesper B. Nielsen and Jørgen T. Lauridsen have no financial interest&#xD;
           in LIVA Healthcare A/S or any other aspects of this study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">April 16, 2018</start_date>
  <completion_date type="Anticipated">March 2021</completion_date>
  <primary_completion_date type="Anticipated">April 2019</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>Treatment</primary_purpose>
    <masking>Double (Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Weight change</measure>
    <time_frame>Baseline, 6, 12, and 24 months</time_frame>
    <description>kg</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>HbA1C change</measure>
    <time_frame>Baseline, 6, 12 and 24 months</time_frame>
    <description>mmol/mol</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Medicine usage change</measure>
    <time_frame>Baseline, 6, 12 and 24 months</time_frame>
    <description>Registration of medicine usage by healthcare professional</description>
  </other_outcome>
  <other_outcome>
    <measure>SF-12 Quality of life change</measure>
    <time_frame>Baseline, 6, 12, and 24 months</time_frame>
    <description>Validated quality of life questionaire SF-12</description>
  </other_outcome>
  <other_outcome>
    <measure>Retention rate change</measure>
    <time_frame>Baseline, 6, 12 and 24 months</time_frame>
    <description>How many users are active in the collaborative eHealth tool/a usual care program</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">340</enrollment>
  <condition>Obesity</condition>
  <arm_group>
    <arm_group_label>Online dietician lifestyle counseling</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Online dietetic lifestyle counseling</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Usual care</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Usual care</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Online dietetic lifestyle counseling</intervention_name>
    <description>The certified clinical dieticians provide individual therapy online and offline according to their patients' needs and based on information supplied via the website &quot;www.livalife.dk&quot;. The dietician generates a daily caloric reduction plan of approximately 1600-4800 KJ based on the patients' diet record. The dietary advice will be standardized and follow the dietary guidelines given at &quot;www.livalife.dk&quot; and the Danish Health Administration (Sundhedsstyrelsen).</description>
    <arm_group_label>Online dietician lifestyle counseling</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Usual care</intervention_name>
    <description>Patients randomized to the control group will be offered to receive usual municipal secondary or tertiary preventive offers.</description>
    <arm_group_label>Usual care</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  BMI ≥ 30 kg/m2 and &lt; 45 kg/m2&#xD;
&#xD;
          -  Aged 18 -70 years&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Fails to provide informed consent&#xD;
&#xD;
          -  Fails to complete the initial questionnaire&#xD;
&#xD;
          -  No Internet access in own home through computer or smartphone&#xD;
&#xD;
          -  Is pregnant or actively trying to get pregnant&#xD;
&#xD;
          -  Experiences serious or life-threatening disease&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jens Søndergaard, Professor</last_name>
    <role>Study Director</role>
    <affiliation>University of Southern Denmark</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Research Unit for General Practice, Department for Public Health, University of Southern Denmark</name>
      <address>
        <city>Odense</city>
        <state>Region Of Southern Denmark</state>
        <country>Denmark</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Carl J Brandt, MD</last_name>
      <phone>+45 2014 1566</phone>
      <email>cbrandt@health.sdu.dk</email>
    </contact>
    <contact_backup>
      <last_name>Jens Søndergaard, PhD</last_name>
      <phone>+45 6550 3830</phone>
      <email>jsoendergaard@health.sdu.dk</email>
    </contact_backup>
    <investigator>
      <last_name>Jens Søndergaard, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Jesper B Nielsen, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Carl J Brandt, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Lægehuset i Stenstrup</name>
      <address>
        <city>Stenstrup</city>
        <zip>5700</zip>
        <country>Denmark</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jacob B Madsen, MD</last_name>
      <phone>63621015</phone>
      <email>info@laegehusetistenstrup.dk</email>
    </contact>
    <contact_backup>
      <last_name>Cees Stauvenuiter, MD</last_name>
      <phone>63621015</phone>
      <email>info@laegehusetistenstrup.dk</email>
    </contact_backup>
    <investigator>
      <last_name>Jacob B Madsen, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Cees Stavenuiter, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <link>
    <url>http://www.livahealthcare.com</url>
    <description>Liva Healthcare Collaborative eHealth solution</description>
  </link>
  <reference>
    <citation>Afshin A, Babalola D, Mclean M, Yu Z, Ma W, Chen CY, Arabi M, Mozaffarian D. Information Technology and Lifestyle: A Systematic Evaluation of Internet and Mobile Interventions for Improving Diet, Physical Activity, Obesity, Tobacco, and Alcohol Use. J Am Heart Assoc. 2016 Aug 31;5(9):e003058. doi: 10.1161/JAHA.115.003058.</citation>
    <PMID>27581172</PMID>
  </reference>
  <reference>
    <citation>Johansen MY, MacDonald CS, Hansen KB, Karstoft K, Christensen R, Pedersen M, Hansen LS, Zacho M, Wedell-Neergaard AS, Nielsen ST, Iepsen UW, Langberg H, Vaag AA, Pedersen BK, Ried-Larsen M. Effect of an Intensive Lifestyle Intervention on Glycemic Control in Patients With Type 2 Diabetes: A Randomized Clinical Trial. JAMA. 2017 Aug 15;318(7):637-646. doi: 10.1001/jama.2017.10169.</citation>
    <PMID>28810024</PMID>
  </reference>
  <reference>
    <citation>Lean ME, Leslie WS, Barnes AC, Brosnahan N, Thom G, McCombie L, Peters C, Zhyzhneuskaya S, Al-Mrabeh A, Hollingsworth KG, Rodrigues AM, Rehackova L, Adamson AJ, Sniehotta FF, Mathers JC, Ross HM, McIlvenna Y, Stefanetti R, Trenell M, Welsh P, Kean S, Ford I, McConnachie A, Sattar N, Taylor R. Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. Lancet. 2018 Feb 10;391(10120):541-551. doi: 10.1016/S0140-6736(17)33102-1. Epub 2017 Dec 5.</citation>
    <PMID>29221645</PMID>
  </reference>
  <reference>
    <citation>Brandt V, Brandt CJ, Glintborg D, Arendal C, Toubro S, Brandt K. Sustained weight loss during 20 months using a personalized interactive internet based dietician advice program in a general practice setting. International Journal on Advances in Life Sciences [Internet]. 2011; 3(1&amp;2):[23-8 pp.].</citation>
  </reference>
  <reference>
    <citation>Haste A, Adamson AJ, McColl E, Araujo-Soares V, Bell R. Web-Based Weight Loss Intervention for Men With Type 2 Diabetes: Pilot Randomized Controlled Trial. JMIR Diabetes. 2017 Jul 7;2(2):e14. doi: 10.2196/diabetes.7430.</citation>
    <PMID>30291100</PMID>
  </reference>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>June 16, 2015</study_first_submitted>
  <study_first_submitted_qc>December 24, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 28, 2018</study_first_posted>
  <last_update_submitted>December 24, 2018</last_update_submitted>
  <last_update_submitted_qc>December 24, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 28, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Southern Denmark</investigator_affiliation>
    <investigator_full_name>Carl J. Brandt</investigator_full_name>
    <investigator_title>MD, PhD, Principal investigator</investigator_title>
  </responsible_party>
  <keyword>obesity</keyword>
  <keyword>internet community</keyword>
  <keyword>treatment; preventive medicine</keyword>
  <keyword>risk perception</keyword>
  <keyword>lifestyle counseling</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Weight Loss</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>The study protocol along with the statistical analysis plan (SAP) will be published and all data from the study will be made available in a clinical study report.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>The protocol along with SAP and some of the preliminary results after 6 months will be published within 18 months from start of study.&#xD;
The clinical study report (CSR) will be published within 12 months of the end of the study.</ipd_time_frame>
    <ipd_access_criteria>Study protocol and SAP will be published in international peer review journals and the CSR will at a minimum be made available via the internet through SDU and Researchgate</ipd_access_criteria>
  </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/NCT03788915
org study id: LIVA USouthernDenmark
nct id: NCT03788915
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Background: Systematic reviews conclude that Internet and mobile interventions can
      significantly change lifestyle in a short time span. The applicant has developed a
      collaborative eHealth tool (LIVA) that has led to a significant and clinically relevant
      weight loss of 5.4 to 7.0 kg over 12 to 20 months in primary care settings. The objective of
      this study is to develop and evaluate a model targeting long-term effects using eHealth
      coaching assisted by machine learning-generated advice intervention for overweight patients
      at risk of developing diabetes as well as current type 2 diabetes (T2D) patients in a primary
      care setting.

      Methods and analysis: Randomized controlled trial with 1-year intervention and 1-year
      maintenance. The primary outcome is weight loss and the secondary outcome is reduced HbA1c
      level. The study will comprise 340 overweight patients of which 170 will have T2D. Individual
      data will be obtained from clinical measurements, questionnaire data, registered from the
      collaborative eHealth tool, as well as other registry data at baseline and at 6, 12 and 24
      months. The core of the intervention is the establishment of an empathic relationship and
      ongoing real-life coaching using the LIVA app (working together with native iOS and Android)
      and Internet for patients combined with an effective coaching module supported by machine
      learning methods. The intervention will be compared with usual care.
1. Introduction With diseases such as Type 2 diabetes (T2D), adiposity and cardiovascular
           diseases rapidly increasing, cost effective management is needed (World Health
           Organization, 2017). Lifestyle improvements such as weight loss, diet and exercise
           managed in a primary care setting has shown significant impact on reduced risk of
           cardiovascular disease and reversing T2D for 46-56% of patients with T2D (Lean et al.,
           2017, Johansen et al., 2017). Based on these findings, weight loss among overweight
           patients with T2D and patients at risk of developing T2D has important clinical and
           societal effects.

           Traditional lifestyle interventions are mostly ineffective and expensive long-term.
           Internet and mobile technology-based interventions aiming at promoting healthy
           lifestyles have shown potential for scalability, accessibility, and cost effective use
           in primary care settings both for overweight patients and T2D patients (Brandt et al,
           2011, Haste et al., 2017, Komkova et al 2018). However, there is only sparse knowledge
           about whether the beneficial effects are long-term (Afshin et al., 2016, Levine et al.,
           2015).

           Qualitative research studies comprising patients, general practitioners and the
           healthcare professionals' perspectives suggest that the establishment of an empathic
           relationship is key to long-term lifestyle change (Brandt et al., 2018a, 2018b and
           2018c). An observational study among 103 diabetes patients using the collaborative
           eHealth tool (LIVA) demonstrated a clinically significant self-reported weight loss of
           4.7 kg among users who had been on the platform for 90+ days (Komkova et al., 2018).
           Modelling the association between weight reduction and decreased health care costs, the
           same study estimated that the program will save 2,667€ annually for every patient and be
           cost effective from a municipal perspective even with only 1 year of implementation data
           for T2D patients (Mukherjee et al., 2016, Nichols et al., 2016, Bell et al., 2014).

           In the present study, the model to be tested is a lifestyle intervention using a
           cost-effective eHealth coaching tool (LIVA) model: following an initial meeting,
           frequent digital communication is established between health coach and patient,
           supplemented by machine learning. Machine learning is performed using data automatically
           gathered from patients' relevant daily lifestyle registrations such as activity level,
           step count, diet goals fulfilment, sleep, etc. Data will be analysed to predict
           attrition and outcome. The developed algorithms and models will then be used to increase
           outcome and decrease dropout by supporting the health coaches with information and
           guidance how to deliver better coaching directly and indirectly. This intervention will
           be compared with standard lifestyle interventions in a municipality setting.

        2. Study objectives and hypothesis The aim of this study is to evaluate the clinical
           efficacy of the LIVA intervention for overweight patients at risk of developing a
           chronic disease and overweight type 2 diabetes patients in a primary care setting. We
           hypothesize that the LIVA intervention will lead to significant weight loss, reduced
           HbA1C, and reduced need for medication compared to usual care.

        3. Methods and analysis Study design and setting The study is a randomized controlled trial
           with one year of intervention and one year of subsequent maintenance, with continued
           collection of clinical and questionnaire data, where the primary endpoint is weight loss
           and the secondary endpoint is HbA1c. The intervention is conducted in a real life
           setting; all data management will be at the Research Unit for General Practice,
           Department of Public Health, Primary trial sponsor, J.B. Winsløwsvej 9A, 5000 Odense C,
           Denmark. Recruitment of patients to the study is in 8-10 municipalities within the
           Region of Southern Denmark and the Capitol Region of Denmark. The study has been
           registered at https://register.clinicaltrials.gov. On-boarding of patients began in
           March 2018 and the results are expected to be accessible during 2021.

           Study population and inclusion criteria Flow of patients is described in figure 1. In
           each municipality, advertising through social media will be used to recruit eligible
           patients for municipal preventive offers, fulfilling the inclusion criteria in the study
           (Table 1). These patients will be contacted by phone and/ or email, and informed about
           the study and asked to register if they accept the offer to participate.

           Table 1. Inclusion and exclusion criteria

           Inclusion criteria:

           BMI 45 ≥ 30 kg/m2 Aged 18 -70 years

           Exclusion criteria:

           Fails to provide informed consent Fails to complete the initial questionnaire or
           understand Danish No Internet access in own home through computer or smartphone Is
           pregnant or actively trying to get pregnant Experiences mental or serious
           life-threatening disease

           The 340 eligible patients will be invited to an introduction meeting with an healthcare
           professional with a master's in human nutrition or a clinical dietician. This
           introductory appointment is scheduled within 7-14 days after the information material is
           received by the patient. The patient is weighed and measured according to defined
           clinical indicators. Blood indicators are measured through a finger prick blood sample.
           The patient is then instructed to use a web link to complete a standard quality of life
           questionnaire (SF-12) combined with registration of medication intake and questions
           concerning the patient's sociodemographic characteristics, such as educational level,
           labour market affiliation, questions concerning work performance, and disease history.

           Randomization:

           After patients have successfully completed the web questionnaire, they will be
           randomized via an automated computer algorithm. This procedure ensures that drop-out
           characteristics can be recorded. Patients are randomized in a 60:40 sequencing, where
           60% of recruited patients are randomized for the intervention group while the remaining
           40% will constitute the control group, based on sample size calculations (Please see
           Sample size calculations, below). Randomization is controlled to ensure that 50% of
           intervention group and controls will be overweight patients at risk of developing
           chronic disease and the other 50% of intervention group and controls will be overweight
           diabetes patients.

           Intervention:

           The intervention is summarised in Table 2. Based on results in the applicant's PhD
           thesis, the core of the intervention is the initial establishment of an empathic
           relationship with a healthcare professional who is a clinical dietician by profession
           and has been working with eHealth lifestyle coaching for more than 2 years (referred to
           as the health coach) and who delivers effective remote and/or digital coaching
           responsive to the users' own data registrations (Brandt et al, 2018a). Patients in the
           intervention group receive a login to the eHealth tool at a personal meeting (either
           physical or digital) during which the health coach introduces the program. Together, the
           patient and the health coach agree on goals for diet, physical exercise, sleep, etc.
           (Brandt et al, 2018b). Using the app, patients fill in a daily record as well as their
           comments, concerns and questions for the health coach, who will have access to patient
           profiles. The health coach provides individual asynchronous advice according to the
           patients' needs based on the patients' own real-time registrations (Brandt et al,
           2018c); the health coach's advice is supported by artificial intelligence predictions
           using machine learning (Holzinger A. et al, 2017). The coach advises on goal setting
           based on the SMART model: Specific, Measurable, Attainable, Relevant, Timely, and
           according to a predefined guideline structure (Ryan et al, 2009).

           Asynchronous advice will be provided on a weekly basis during the first 6 months.
           Subsequently, advice will be given monthly for 6 months. After 12 months, the
           participant enters maintenance for 12 months, where the coach will still follow
           patients' registrations and may give four to twelve coaching sessions during that year.
           Patients can also participate in usual municipally provided preventive medicine
           offerings, such as "diabetes school", to the extent that the municipalities normally
           provide such offers.

           Conventional care (control group):

           Patients randomized to the control group will be offered standard municipal secondary or
           tertiary preventive offers.

           Study endpoints and assessment:

           Measurement of endpoints (weight, HbA1c etc.) will be conducted by the health coach at
           baseline and at 6, 12 and 24 months' follow-up.

           Primary outcome:

           Weight loss from baseline to 12 months' follow-up.

           Secondary outcome Reduction in HbA1c for all patients from baseline to 12 months for
           patients with T2D.

           Other outcomes

           The following tertiary outcomes will be measured at baseline and at 12 months:

             -  Retention rates among users

             -  Patient waist circumference

             -  Blood pressure

             -  Total cholesterol, LDL, HDL and TG

             -  Patients' quality of life

             -  Changes in patterns of medication Apart from these outcomes, patient demographic
                characteristics (gender, age, highest educational level) will be measured at
                baseline.

           Analysis strategy Primary analyses will be performed blinded by statisticians and
           comprise subgroup analyses based on stratification according to patient characteristics
           and experiences. Statistical significance will be inferred at a two-tailed and p<0.05
           significance level. All data will be accessible on the Internet in anonymised form to
           allow full peer scrutiny and facilitate secondary research.

           Sample size calculations The primary objective of this study is measurement of changes
           in body weight and waist circumference. Weight loss in the intervention group and
           control group will be analysed using appropriate statistical procedures. Based on a
           recent study by Haste and colleagues evaluating a web-based weight loss intervention
           among men with diabetes, we expect a weight loss of at least 4.5 kg at 12 months in the
           intervention group, compared to 2.5 kg in the control group, as well as dropout rates of
           39% among the intervention group and 57% among control group at 12 months (Haste et al.,
           2017). A power calculation based on the standard deviations observed in the study
           performed by Haste et al shows that to detect a difference in weight loss of 2 kg with a
           power of 0.95% requires 55 patients in the intervention group and 32 in the control
           group. To be able to stratify analyses according to overweight patients at risk of
           developing chronic disease and overweight diabetes patients we will therefore recruit
           200 (100+100) in the intervention groups and 140 (70+70) controls.

        4. Ethics The intervention is not expected to cause any side effects or discomfort except
           for the ones a change in lifestyle can bring. The only recognized risk is in relation to
           eating disorders (pre-existing or developing during the study) and the dieticians and
           nurses involved in the study will specifically look out for indications of this. The
           Regional Ethical Committee (Regional Videnskabsetisk Komité) have accepted the study in
           according to Danish law. Participant data will be handled and stored in accordance with
           rules approved by the Danish Data Inspectorate (Datatilsynet). Permission to handle
           individual patient data from the national registries will be obtained from patients and
           the Danish Data Inspectorate. All data will be analysed in anonymous form.

        5. Publication The results of the studies will be published in international journals in
           accordance with the Vancouver rules. Furthermore, participants will be invited to a
           presentation of results at the end of the study and news media will be informed.

        6. Conflict of Interests Carl J. Brandt has co-founded and works as a medical consultant
           for LIVA Healthcare A/S, the company that has developed parts of the technical platform
           and will host some of it during the study. Carl J. Brandt works at the Research Unit for
           General Practice and CIMT at SDU. Camilla Sortsø is working for LIVA Healthcare A/S,
           Jens Søndergaard, Jesper B. Nielsen and Jørgen T. Lauridsen have no financial interest
           in LIVA Healthcare A/S or any other aspects of this study.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Investigator, Outcomes Assessor)
measure: Weight change
time frame: Baseline, 6, 12, and 24 months
description: kg
measure: HbA1C change
time frame: Baseline, 6, 12 and 24 months
description: mmol/mol
measure: Medicine usage change
time frame: Baseline, 6, 12 and 24 months
description: Registration of medicine usage by healthcare professional
measure: SF-12 Quality of life change
time frame: Baseline, 6, 12, and 24 months
description: Validated quality of life questionaire SF-12
measure: Retention rate change
time frame: Baseline, 6, 12 and 24 months
description: How many users are active in the collaborative eHealth tool/a usual care program
arm group label: Online dietician lifestyle counseling
arm group type: Active Comparator
description: Online dietetic lifestyle counseling
arm group label: Usual care
arm group type: Placebo Comparator
description: Usual care
intervention type: Behavioral
intervention name: Online dietetic lifestyle counseling
description: The certified clinical dieticians provide individual therapy online and offline according to their patients' needs and based on information supplied via the website "www.livalife.dk". The dietician generates a daily caloric reduction plan of approximately 1600-4800 KJ based on the patients' diet record. The dietary advice will be standardized and follow the dietary guidelines given at "www.livalife.dk" and the Danish Health Administration (Sundhedsstyrelsen).
arm group label: Online dietician lifestyle counseling
intervention type: Behavioral
intervention name: Usual care
description: Patients randomized to the control group will be offered to receive usual municipal secondary or tertiary preventive offers.
arm group label: Usual care
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Jens Søndergaard, Professor
role: Study Director
affiliation: University of Southern Denmark
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
country: Denmark
url: http://www.livahealthcare.com
description: Liva Healthcare Collaborative eHealth solution
citation: Afshin A, Babalola D, Mclean M, Yu Z, Ma W, Chen CY, Arabi M, Mozaffarian D. Information Technology and Lifestyle: A Systematic Evaluation of Internet and Mobile Interventions for Improving Diet, Physical Activity, Obesity, Tobacco, and Alcohol Use. J Am Heart Assoc. 2016 Aug 31;5(9):e003058. doi: 10.1161/JAHA.115.003058.
PMID: 27581172
citation: Johansen MY, MacDonald CS, Hansen KB, Karstoft K, Christensen R, Pedersen M, Hansen LS, Zacho M, Wedell-Neergaard AS, Nielsen ST, Iepsen UW, Langberg H, Vaag AA, Pedersen BK, Ried-Larsen M. Effect of an Intensive Lifestyle Intervention on Glycemic Control in Patients With Type 2 Diabetes: A Randomized Clinical Trial. JAMA. 2017 Aug 15;318(7):637-646. doi: 10.1001/jama.2017.10169.
PMID: 28810024
citation: Lean ME, Leslie WS, Barnes AC, Brosnahan N, Thom G, McCombie L, Peters C, Zhyzhneuskaya S, Al-Mrabeh A, Hollingsworth KG, Rodrigues AM, Rehackova L, Adamson AJ, Sniehotta FF, Mathers JC, Ross HM, McIlvenna Y, Stefanetti R, Trenell M, Welsh P, Kean S, Ford I, McConnachie A, Sattar N, Taylor R. Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. Lancet. 2018 Feb 10;391(10120):541-551. doi: 10.1016/S0140-6736(17)33102-1. Epub 2017 Dec 5.
PMID: 29221645
citation: Brandt V, Brandt CJ, Glintborg D, Arendal C, Toubro S, Brandt K. Sustained weight loss during 20 months using a personalized interactive internet based dietician advice program in a general practice setting. International Journal on Advances in Life Sciences [Internet]. 2011; 3(1&2):[23-8 pp.].
citation: Haste A, Adamson AJ, McColl E, Araujo-Soares V, Bell R. Web-Based Weight Loss Intervention for Men With Type 2 Diabetes: Pilot Randomized Controlled Trial. JMIR Diabetes. 2017 Jul 7;2(2):e14. doi: 10.2196/diabetes.7430.
PMID: 30291100
responsible party type: Principal Investigator
investigator affiliation: University of Southern Denmark
investigator full name: Carl J. Brandt
investigator title: MD, PhD, Principal investigator
mesh term: Weight Loss
sharing ipd: Yes
ipd description: The study protocol along with the statistical analysis plan (SAP) will be published and all data from the study will be made available in a clinical study report.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Clinical Study Report (CSR)
ipd time frame: The protocol along with SAP and some of the preliminary results after 6 months will be published within 18 months from start of study.
The clinical study report (CSR) will be published within 12 months of the end of the study.
ipd access criteria: Study protocol and SAP will be published in international peer review journals and the CSR will at a minimum be made available via the internet through SDU and Researchgate