<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/NCT03305939</url>
  </required_header>
  <id_info>
    <org_study_id>LIVING</org_study_id>
    <nct_id>NCT03305939</nct_id>
  </id_info>
  <brief_title>Lifestyle Intervention IN Gestational Diabetes (LIVING)</brief_title>
  <acronym>LIVING</acronym>
  <official_title>A Lifestyle Intervention Program for the Prevention of Type 2 Diabetes Mellitus Among South Asian Women With Prior Gestational Diabetes Mellitus.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The George Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Health and Medical Research Council, Australia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>All India Institute of Medical Sciences, New Delhi</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>The George Institute</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>
      Investigators have taken the learning from various programs to develop a new lifestyle&#xD;
      program (LIVING) that has a high probability of being feasible, acceptable and cost-effective&#xD;
      in the South Asian context for women with prior Gestational Diabetes Mellitus (GDM).&#xD;
      Investigators will optimize this intervention using an iterative, systems-based and&#xD;
      user-centered approach. The intervention will be delivered by auxiliary nurse midwives or&#xD;
      their equivalent in each participating hospital, representing a strategy of within-system&#xD;
      task-shifting to augment scalability and sustainability. Investigators will then evaluate&#xD;
      this in a Randomised Controlled Trial (RCT) to determine whether it will reduce the incidence&#xD;
      of Type 2 Diabetes Mellitus (T2DM), in a manner that is affordable, acceptable and scalable.&#xD;
      This project focuses on generating new knowledge around implementation of a preventive&#xD;
      strategy embedded within existing health systems, using mixed-methods evaluation to inform on&#xD;
      cost-effectiveness, acceptability and scalability. It represents a case study into&#xD;
      &quot;Integrated Innovation TM&quot; incorporating a science component (a program based on behavior&#xD;
      change theory that supports a multi-level approach to prevention by combining individually&#xD;
      targeted strategies with social support), a social component (an innovative workforce&#xD;
      strategy) and a sustainability component (a systems perspective for integration with existing&#xD;
      health system infrastructure).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Burden: Diabetes Mellitus is a major public health concern for both the developed and the&#xD;
      developing countries. Globally 246 million people are affected with diabetes, and this will&#xD;
      rise to 300 million by 2025. In India, around 25% of the 25 million pregnancies are&#xD;
      associated with GDM, and this is increasing rapidly over time. Reported prevalence rates for&#xD;
      GDM in Sri Lanka and Bangladesh are 13% and 10% respectively, although the Bangladesh&#xD;
      estimate varied from 9.7% to 12.9% when different criteria were used.&#xD;
&#xD;
      Knowledge gap: There is knowledge gap on whether a resource- and culturally-appropriate&#xD;
      lifestyle intervention program will be more effective and cost effective relative to usual&#xD;
      care in delaying or preventing incidence of T2D among women in South Asia. Evidence from&#xD;
      developed countries indicates that a low-intensity lifestyle intervention, integrated with&#xD;
      antenatal care in the health system, optimizes healthy diet and attenuates physical activity&#xD;
      decline in early pregnancy.&#xD;
&#xD;
      Study Design: An open-label parallel group pragmatic individual RCT with blinded primary&#xD;
      endpoint adjudication will be performed. The RCT will be preceded by an intervention&#xD;
      development and optimization phase.&#xD;
&#xD;
      Study Setting: This is an individual RCT in 1414 women from 24 hospitals (approx) in India&#xD;
      (700 participants from 10-12 hospitals), Bangladesh (350 participants from 4 hospitals) and&#xD;
      Sri Lanka (350 participants from 4 hospitals).&#xD;
&#xD;
      Sample Size: The inclusion of 1414 women with GDM from 24 hospitals (~60/hospital) will&#xD;
      provide 90% power (2α=0.05) to detect a relative risk of ≤0.65, assuming that the control&#xD;
      group cumulative incidence for change in glycaemic category will be at least 20% (median&#xD;
      follow-up 24 months), and allowing for 20% drop out from trial (data) follow-up. A key&#xD;
      secondary outcome is body weight; inclusion of 1414 women will provide 90% power to detect a&#xD;
      difference of 1.8kg (assuming mean body weight of 64.2kg [sd 10.4]) in a control group.&#xD;
&#xD;
      The selection process of the respondents for the full scale trial: Study staff will recruit&#xD;
      women with GDM at 24 to 34 weeks of gestation through a standard Oral Glucose tolerance test&#xD;
      (OGTT) following International Association of the Diabetes and Pregnancy Study Groups&#xD;
      (IADPSG) criteria. If a patient has undergone assessment of glycaemic status prior to 24&#xD;
      weeks' gestation, an OGTT is performed to confirm the diagnosis between 24 and 34 weeks'&#xD;
      gestation, unless she is treated with an oral hypoglycaemic drug and/or insulin before 24&#xD;
      weeks, and satisfies the IADPSG criteria for diagnosis of GDM. If only Fasting Plasma Glucose&#xD;
      (FPG) was done at 24-34 weeks, then the patient is categorized as GDM/overt diabetes/ normal&#xD;
      on the basis of FPG value alone.&#xD;
&#xD;
      The inclusion criteria are the absence of T2DM (i.e. confirmation of Normal Glucose Tolerance&#xD;
      (NGT), Impaired Fasting Glucose (IFG) or Impaired Glucose Tolerance (IGT)) at 3 to 18 months&#xD;
      post-partum OGTT.&#xD;
&#xD;
      Program specific training: Site training will occur prior to enrollment of study&#xD;
      participants. Training will be done either by the Central Coordinating Center (CCC) directly&#xD;
      or through a trained member at the Regional Coordinating Center (RCC).Prior to finalizing the&#xD;
      intervention, it will be optimized in a substantive formative phase in each participating&#xD;
      country, to develop the training module and finalize the content and mode of intervention&#xD;
      delivery. In each participating country, a barriers analysis through formative phase has been&#xD;
      conducted to understand local contextual factors.&#xD;
&#xD;
      For stage 2: After 3 to 18 months of delivery childbirth, each individual respondent who&#xD;
      consented at stage 1 to be contacted for participation in the study will be approached again&#xD;
      for a post-partum OGTT. Those who will be diagnosed as Impaired Glucose Tolerance (IGT) or&#xD;
      Impaired fasting Glucose (IFG) or with normal glycaemic status, and satisfy all inclusion&#xD;
      criteria, will be enrolled in the study for the next 3 years. Those individuals diagnosed&#xD;
      with T2DM will be excluded from the study and will be referred to the usual care of an&#xD;
      endocrinologist.&#xD;
&#xD;
      Assignment of interventions: Allocation procedure (Randomization):&#xD;
&#xD;
      Participants will be recruited and then randomly allocated to intervention and control arms&#xD;
      by central concealed randomization. Randomization will be conducted through a central,&#xD;
      computer-based randomization service, and will be stratified by country; site and use of&#xD;
      insulin during pregnancy.&#xD;
&#xD;
      Blinding: By necessity, neither site investigators nor participants will be blinded to&#xD;
      allocation (intervention vs. usual care). However, all central study staff, statisticians and&#xD;
      outcome adjudicators will remain blinded until final database lock.&#xD;
&#xD;
      Study arms: The intervention will include 4 face-to-face group sessions combined with remote&#xD;
      on-going support, and an intensification offering when needed. However depending on outcomes&#xD;
      during the optimization phase, the balance of face-to-face and remote contact might vary&#xD;
      substantially overall and between countries. The intervention group will be linked up with&#xD;
      the facilitator and will be followed up by the outcome assessor. Face-to-face sessions will&#xD;
      be delivered by a trained facilitator using the existing Help-her training program optimized&#xD;
      for each country. Eligible and consenting women will attend group sessions comprising not&#xD;
      more than 10 women and will have baseline measures assessed prior to the commencement of the&#xD;
      program. During session 1 the respondents will receive a program specific user manual and&#xD;
      over the following weeks work through the behavioral skills sessions with the intervention&#xD;
      facilitator. The participant manuals developed for the PregDiabCare pilot will undergo minor&#xD;
      adaption for use in each country. Each session will last for 90 minutes. Following the face&#xD;
      to face visits participants will also receive reminders and motivational messages related to&#xD;
      small actionable behaviors delivered using mobile text /voice messages adapted from the World&#xD;
      Health Organisation (WHO) Be He@lthy Be MOBILE manual.&#xD;
&#xD;
      In addition, at 26 weeks from the commencement of the intervention, women will undergo a&#xD;
      review of progress. Program intensification will be offered to women who gain more than 2% of&#xD;
      baseline weight (which accounts for transient weight fluctuations) will receive two&#xD;
      intensification sessions of individualized coaching, and monthly phone coaching for the&#xD;
      remaining 6 months, delivered by the trained facilitators. All phases of the program focus on&#xD;
      self-management through small, feasible, and sustainable changes, by building knowledge and&#xD;
      skills across 3 themes (1) simple healthy eating and moderate physical activity messages; 2)&#xD;
      behavioral skills such as problem-solving / goal-setting / self-monitoring; and 3) enhancing&#xD;
      internal motivation, self-efficacy, and self-management.&#xD;
&#xD;
      All participants will undergo six monthly follow up, including data collection by using&#xD;
      specific case record forms (CRF) and blood sample collection to check the blood glucose level&#xD;
      using HbA1c and OGTT at alternate 6 month follow up visits. If the HbA1c value is more than&#xD;
      6.5%, the participant is called for an OGTT. Participants who develop T2DM will not be&#xD;
      followed up further. Participants who change glycaemic category but do not develop T2DM, as&#xD;
      well as participants who continue in their glycaemic category, will be followed up.&#xD;
&#xD;
      Control group participants will be referred to their usual doctor for ongoing management,&#xD;
      with no attempt made to influence this. Any abnormal OGTT results during follow up will be&#xD;
      provided to the patient and their doctor. This is entirely consistent with current usual&#xD;
      care.&#xD;
&#xD;
      Primary outcome: Proportion of women with change of glycaemic category, at or prior to final&#xD;
      visit; from Normal Glucose Tolerance to Impaired Fasting Glucose (IFG) or Impaired Glucose&#xD;
      Tolerance (IGT) or T2DM; or Impaired Fasting Glucose (IFG) or Impaired Glucose Tolerance&#xD;
      (IGT) to Type 2 Diabetes Mellitus (T2DM).&#xD;
&#xD;
      Secondary outcomes: Mean change in fasting blood glucose, mean change in body weight ,mean&#xD;
      change in waist circumference (cm), changes in mean systolic blood pressure (SBP),mean change&#xD;
      in physical activity level , change in diet.&#xD;
&#xD;
      Data collection methods: Data will be collected at randomization and 6 monthly intervals&#xD;
      thereafter, involving a brief case record form, with additional OGTT and HbA1c tests,&#xD;
      alternately conducted at the follow up 6 monthly visits and both tests at the End of Study&#xD;
      visit. Data will be captured electronically and data management will strictly comply with&#xD;
      International Conference on Harmonisation - Good Clinical Practice (ICH-GCP) guidelines,&#xD;
      utilizing Standard Operating Procedures established at participating institutes. Monitoring&#xD;
      will be used to ensure quality and completeness of data, with an emphasis on central&#xD;
      statistical monitoring to minimize costs.&#xD;
&#xD;
      Data Analysis plan: Analysis will be based on the principle of intention-to-treat. The&#xD;
      effectiveness of the study intervention on the primary outcomes will be determined using Cox&#xD;
      models for survival data, with censoring of participants who develop a subsequent pregnancy&#xD;
      or type 2 DM during follow-up. Analyses of secondary outcomes will be conducted using&#xD;
      standard statistical procedures applicable to dichotomous, categorical or continuous data as&#xD;
      appropriate. However, any country level change detected during the analyses will be reported.&#xD;
&#xD;
      Research Ethics Approval: Ethics approval has been obtained from a number of ethics&#xD;
      committees, including the University of Sydney Human Research Ethics Committee. In India,&#xD;
      approvals from the Health Ministry Screening Committee and the All India Institute of Medical&#xD;
      Sciences (Central Coordinating Centre) have been obtained as have approvals from each&#xD;
      participating hospital. In Sri Lanka, approval has been obtained from the Ethics Review&#xD;
      Committee, Faculty of Medicine, University of Kelaniya, which is accredited by the Ministry&#xD;
      of Health. In Bangladesh, ethics committee approval from icddr,b has been obtained to allow&#xD;
      involvement of all hospitals. The trial is registered with the Clinical Trials Registries of&#xD;
      India and Sri Lanka.&#xD;
&#xD;
      Consent: Participants willing to take part in the study will be consented by trial centres&#xD;
      using a two-stage consent process with written informed consent being obtained both at&#xD;
      initial engagement during pregnancy, as well as prior to randomisation. Participants will be&#xD;
      given adequate explanation about the study and will be given ample time to consider their&#xD;
      trial participation. They will be given the opportunity to ask questions about the trial and&#xD;
      what their participation involves, and will receive clarification from the investigator and&#xD;
      other study staff. A written informed consent form (using appropriately translated versions&#xD;
      where appropriate) will be signed and personally dated by the subject or by the subject's&#xD;
      legally acceptable representative, and by the person who conducted the informed consent&#xD;
      discussion. If a subject is unable to read or if a legally acceptable representative is&#xD;
      unable to read, an impartial witness should be present during the entire informed consent&#xD;
      discussion and must attest the written informed consent form. A copy of the signed written&#xD;
      informed consent form will be given to the trial participant.&#xD;
&#xD;
      Donor: The study is funded under Global Alliance for Chronic Diseases (GACD) Grant&#xD;
      (APP1093171) by National Health and Medical Research Council of Australia (NHMRC) and Indian&#xD;
      Council of Medical Research (ICMR) GACD Grant.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 1, 2017</start_date>
  <completion_date type="Actual">January 31, 2021</completion_date>
  <primary_completion_date type="Actual">January 31, 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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of women with a change of glycaemic category, at or prior to final visit</measure>
    <time_frame>3 years</time_frame>
    <description>From Normal Glucose Tolerance to Impaired Fasting Glucose (IFG) or Impaired Glucose Tolerance (IGT) or T2DM; or Impaired Fasting Glucose (IFG) or Impaired Glucose Tolerance (IGT) to Type 2 Diabetes Mellitus (T2DM).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in fasting blood glucose as assessed by OGTT</measure>
    <time_frame>3 years</time_frame>
    <description>Mean Change in fasting blood glucose status during the study period among the respondents</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in body weight as assessed by the standard study weighing scale</measure>
    <time_frame>3 years</time_frame>
    <description>Mean change in body weight during the study period among the respondents.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in waist circumference (in cm) as assessed by the standard study measuring tape</measure>
    <time_frame>3 years</time_frame>
    <description>Mean change in waist circumference (in cm) during the study period among the respondents.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in systolic blood pressure (SBP) as assessed by Omron BP measuring machine</measure>
    <time_frame>3 years</time_frame>
    <description>Changes in mean systolic blood pressure (SBP) during the study period among the respondents.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in physical activity level as assessed by Modified Global Physical Activity Questionnaire (MGPAQ)</measure>
    <time_frame>3 years</time_frame>
    <description>Mean change in physical activity level during the study period among the respondents.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in dietary habits as assessed by Intake 24 (a 24-hour recall questionnaire)</measure>
    <time_frame>3 years</time_frame>
    <description>Mean change in dietary practice during the study period among the respondents.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">1612</enrollment>
  <condition>Gestational Diabetes Mellitus in Pregnancy</condition>
  <arm_group>
    <arm_group_label>Intervention</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants randomized in to the intervention group will receive group sessions, monthly phone calls, and telephonic prompts (text/voice recording).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Control group participants will be referred to their usual doctor for ongoing management, with no attempt made to influence this. They will not get any part of the intervention but will receive the usual care (if any exists). Any abnormal OGTT results during the follow-up visits will be provided to the patient and their doctor. This is entirely consistent with current usual care.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Life style Intervention</intervention_name>
    <description>The intervention will include 4 face-to-face group sessions in the first 6 months, followed by remote support strategies and intensification counseling sessions when needed. Ongoing support and contact shown to be important in supporting behavior change will consist of reminders, and motivational messages for small actionable behaviors, delivered using mobile text or voice messages. Program intensification will be offered to women who fail to meet their weight goals by the 6 month time point. All phases of the program focus on self- management across 3 themes&#xD;
simple healthy eating and moderate physical activity messages;&#xD;
behavioral skills such as problem solving/goal setting/self-monitoring; and&#xD;
enhancing internal motivation, self-efficacy and self-management. The program is deliberately not prescriptive, and has a focus on sustainable behaviors and local context.</description>
    <arm_group_label>Intervention</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  The inclusion criteria will be the absence of T2DM (i.e. confirmation of NGT, IFG or&#xD;
             IGT) at 3 to 18 months post-partum OGTT.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Exclusion criteria will be limited to:&#xD;
&#xD;
        Travel time to hospital more than 2 hours (unless individual circumstances will not impede&#xD;
        hospital attendance for study visits), lack of access to a mobile telephone, use of&#xD;
        steroids during pregnancy (other than for lung maturation of the baby), confirmed case of&#xD;
        Type 2 Diabetes, likelihood of moving residence in the next 3 years, refused consent .&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Participants must be women</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Anushka Patel, Ph.D</last_name>
    <role>Principal Investigator</role>
    <affiliation>The George Institute</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Nikhil Tandon, Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>All India Institute of Medical Sciences, New Delhi</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Marie Stopes Clinic</name>
      <address>
        <city>Dhaka</city>
        <zip>1207</zip>
        <country>Bangladesh</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azimpur Matenity Clinic</name>
      <address>
        <city>Dhaka</city>
        <country>Bangladesh</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>BIRDEM (Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders)</name>
      <address>
        <city>Dhaka</city>
        <country>Bangladesh</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mohammadpur Fertility Services &amp; Training Centre</name>
      <address>
        <city>Dhaka</city>
        <country>Bangladesh</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>M S Ramaiah Medical College</name>
      <address>
        <city>Bengaluru</city>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>PGIMER</name>
      <address>
        <city>Chandigarh</city>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Madras Diabetes Research Centre</name>
      <address>
        <city>Chennai</city>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Goa Medical College &amp; Hospital</name>
      <address>
        <city>Goa</city>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fernandez Hospital Foundation</name>
      <address>
        <city>Hyderabad</city>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>King Edward Memorial (KEM) Hospital</name>
      <address>
        <city>Mumbai</city>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>TNM College &amp; BYL Nair Ch.Hospital</name>
      <address>
        <city>Mumbai</city>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kalpavriksh Super Speciality Centre</name>
      <address>
        <city>New Delhi</city>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>JIPMER (Jawaharlal Institute of Postgraduate Medical Education and Research)</name>
      <address>
        <city>Puducherry</city>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Maharaja Agrasen Hospital</name>
      <address>
        <city>Punjabi Bagh</city>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Christian Medical College</name>
      <address>
        <city>Vellore</city>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Castle Street Hospital for Women</name>
      <address>
        <city>Colombo</city>
        <country>Sri Lanka</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>De Soyza Maternity Hospital</name>
      <address>
        <city>Colombo</city>
        <country>Sri Lanka</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Colombo South Teaching Hospital</name>
      <address>
        <city>Kalubowila</city>
        <country>Sri Lanka</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Negombo District General Hospital</name>
      <address>
        <city>Negombo</city>
        <country>Sri Lanka</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Colombo North Teaching Hospital</name>
      <address>
        <city>Ragama</city>
        <country>Sri Lanka</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Bangladesh</country>
    <country>India</country>
    <country>Sri Lanka</country>
  </location_countries>
  <reference>
    <citation>Gupta Y, Kapoor D, Josyula LK, Praveen D, Naheed A, Desai AK, Pathmeswaran A, de Silva HA, Lombard CB, Shamsul Alam D, Prabhakaran D, Teede HJ, Billot L, Bhatla N, Joshi R, Zoungas S, Jan S, Patel A, Tandon N. A lifestyle intervention programme for the prevention of Type 2 diabetes mellitus among South Asian women with gestational diabetes mellitus [LIVING study]: protocol for a randomized trial. Diabet Med. 2019 Feb;36(2):243-251. doi: 10.1111/dme.13850. Epub 2018 Nov 29.</citation>
    <PMID>30368898</PMID>
  </reference>
  <reference>
    <citation>Tewari A, Praveen D, Madhira P, Josyula LK, Joshi R, Kokku SB, Garg V, Rawal I, Chopra K, Chakma N, Ahmed S, Pathmeswaran A, Godamunne P, Lata AS, Sahay R, Patel T, Gupta Y, Tandon N, Naheed A, Patel A, Kapoor D. Feasibility of a Lifestyle Intervention Program for Prevention of Diabetes Among Women With Prior Gestational Diabetes Mellitus (LIVING Study) in South Asia: A Formative Research Study. Front Glob Womens Health. 2020 Nov 27;1:587607. doi: 10.3389/fgwh.2020.587607. eCollection 2020.</citation>
    <PMID>34816163</PMID>
  </reference>
  <reference>
    <citation>Shanthosh J, Kapoor D, Josyula LK, Patel A, Gupta Y, Tandon N, Jan S, Teede HJ, Desai A, Joshi R, Praveen D. Lifestyle InterVention IN Gestational diabetes (LIVING) in India, Bangladesh and Sri Lanka: protocol for process evaluation of a randomised controlled trial. BMJ Open. 2020 Dec 13;10(12):e037774. doi: 10.1136/bmjopen-2020-037774.</citation>
    <PMID>33318108</PMID>
  </reference>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>June 21, 2017</study_first_submitted>
  <study_first_submitted_qc>October 9, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 10, 2017</study_first_posted>
  <last_update_submitted>March 21, 2021</last_update_submitted>
  <last_update_submitted_qc>March 21, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 23, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Gestational Diabetes,Lifestyle,Type 2 DM</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes, Gestational</mesh_term>
    <mesh_term>Pregnancy in Diabetics</mesh_term>
    <mesh_term>Diabetes Mellitus</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>To be developed</ipd_description>
    <ipd_time_frame>To be determined</ipd_time_frame>
    <ipd_access_criteria>To de determined</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/NCT03305939
org study id: LIVING
nct id: NCT03305939
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Investigators have taken the learning from various programs to develop a new lifestyle
      program (LIVING) that has a high probability of being feasible, acceptable and cost-effective
      in the South Asian context for women with prior Gestational Diabetes Mellitus (GDM).
      Investigators will optimize this intervention using an iterative, systems-based and
      user-centered approach. The intervention will be delivered by auxiliary nurse midwives or
      their equivalent in each participating hospital, representing a strategy of within-system
      task-shifting to augment scalability and sustainability. Investigators will then evaluate
      this in a Randomised Controlled Trial (RCT) to determine whether it will reduce the incidence
      of Type 2 Diabetes Mellitus (T2DM), in a manner that is affordable, acceptable and scalable.
      This project focuses on generating new knowledge around implementation of a preventive
      strategy embedded within existing health systems, using mixed-methods evaluation to inform on
      cost-effectiveness, acceptability and scalability. It represents a case study into
      "Integrated Innovation TM" incorporating a science component (a program based on behavior
      change theory that supports a multi-level approach to prevention by combining individually
      targeted strategies with social support), a social component (an innovative workforce
      strategy) and a sustainability component (a systems perspective for integration with existing
      health system infrastructure).
Burden: Diabetes Mellitus is a major public health concern for both the developed and the
      developing countries. Globally 246 million people are affected with diabetes, and this will
      rise to 300 million by 2025. In India, around 25% of the 25 million pregnancies are
      associated with GDM, and this is increasing rapidly over time. Reported prevalence rates for
      GDM in Sri Lanka and Bangladesh are 13% and 10% respectively, although the Bangladesh
      estimate varied from 9.7% to 12.9% when different criteria were used.

      Knowledge gap: There is knowledge gap on whether a resource- and culturally-appropriate
      lifestyle intervention program will be more effective and cost effective relative to usual
      care in delaying or preventing incidence of T2D among women in South Asia. Evidence from
      developed countries indicates that a low-intensity lifestyle intervention, integrated with
      antenatal care in the health system, optimizes healthy diet and attenuates physical activity
      decline in early pregnancy.

      Study Design: An open-label parallel group pragmatic individual RCT with blinded primary
      endpoint adjudication will be performed. The RCT will be preceded by an intervention
      development and optimization phase.

      Study Setting: This is an individual RCT in 1414 women from 24 hospitals (approx) in India
      (700 participants from 10-12 hospitals), Bangladesh (350 participants from 4 hospitals) and
      Sri Lanka (350 participants from 4 hospitals).

      Sample Size: The inclusion of 1414 women with GDM from 24 hospitals (~60/hospital) will
      provide 90% power (2α=0.05) to detect a relative risk of ≤0.65, assuming that the control
      group cumulative incidence for change in glycaemic category will be at least 20% (median
      follow-up 24 months), and allowing for 20% drop out from trial (data) follow-up. A key
      secondary outcome is body weight; inclusion of 1414 women will provide 90% power to detect a
      difference of 1.8kg (assuming mean body weight of 64.2kg [sd 10.4]) in a control group.

      The selection process of the respondents for the full scale trial: Study staff will recruit
      women with GDM at 24 to 34 weeks of gestation through a standard Oral Glucose tolerance test
      (OGTT) following International Association of the Diabetes and Pregnancy Study Groups
      (IADPSG) criteria. If a patient has undergone assessment of glycaemic status prior to 24
      weeks' gestation, an OGTT is performed to confirm the diagnosis between 24 and 34 weeks'
      gestation, unless she is treated with an oral hypoglycaemic drug and/or insulin before 24
      weeks, and satisfies the IADPSG criteria for diagnosis of GDM. If only Fasting Plasma Glucose
      (FPG) was done at 24-34 weeks, then the patient is categorized as GDM/overt diabetes/ normal
      on the basis of FPG value alone.

      The inclusion criteria are the absence of T2DM (i.e. confirmation of Normal Glucose Tolerance
      (NGT), Impaired Fasting Glucose (IFG) or Impaired Glucose Tolerance (IGT)) at 3 to 18 months
      post-partum OGTT.

      Program specific training: Site training will occur prior to enrollment of study
      participants. Training will be done either by the Central Coordinating Center (CCC) directly
      or through a trained member at the Regional Coordinating Center (RCC).Prior to finalizing the
      intervention, it will be optimized in a substantive formative phase in each participating
      country, to develop the training module and finalize the content and mode of intervention
      delivery. In each participating country, a barriers analysis through formative phase has been
      conducted to understand local contextual factors.

      For stage 2: After 3 to 18 months of delivery childbirth, each individual respondent who
      consented at stage 1 to be contacted for participation in the study will be approached again
      for a post-partum OGTT. Those who will be diagnosed as Impaired Glucose Tolerance (IGT) or
      Impaired fasting Glucose (IFG) or with normal glycaemic status, and satisfy all inclusion
      criteria, will be enrolled in the study for the next 3 years. Those individuals diagnosed
      with T2DM will be excluded from the study and will be referred to the usual care of an
      endocrinologist.

      Assignment of interventions: Allocation procedure (Randomization):

      Participants will be recruited and then randomly allocated to intervention and control arms
      by central concealed randomization. Randomization will be conducted through a central,
      computer-based randomization service, and will be stratified by country; site and use of
      insulin during pregnancy.

      Blinding: By necessity, neither site investigators nor participants will be blinded to
      allocation (intervention vs. usual care). However, all central study staff, statisticians and
      outcome adjudicators will remain blinded until final database lock.

      Study arms: The intervention will include 4 face-to-face group sessions combined with remote
      on-going support, and an intensification offering when needed. However depending on outcomes
      during the optimization phase, the balance of face-to-face and remote contact might vary
      substantially overall and between countries. The intervention group will be linked up with
      the facilitator and will be followed up by the outcome assessor. Face-to-face sessions will
      be delivered by a trained facilitator using the existing Help-her training program optimized
      for each country. Eligible and consenting women will attend group sessions comprising not
      more than 10 women and will have baseline measures assessed prior to the commencement of the
      program. During session 1 the respondents will receive a program specific user manual and
      over the following weeks work through the behavioral skills sessions with the intervention
      facilitator. The participant manuals developed for the PregDiabCare pilot will undergo minor
      adaption for use in each country. Each session will last for 90 minutes. Following the face
      to face visits participants will also receive reminders and motivational messages related to
      small actionable behaviors delivered using mobile text /voice messages adapted from the World
      Health Organisation (WHO) Be He@lthy Be MOBILE manual.

      In addition, at 26 weeks from the commencement of the intervention, women will undergo a
      review of progress. Program intensification will be offered to women who gain more than 2% of
      baseline weight (which accounts for transient weight fluctuations) will receive two
      intensification sessions of individualized coaching, and monthly phone coaching for the
      remaining 6 months, delivered by the trained facilitators. All phases of the program focus on
      self-management through small, feasible, and sustainable changes, by building knowledge and
      skills across 3 themes (1) simple healthy eating and moderate physical activity messages; 2)
      behavioral skills such as problem-solving / goal-setting / self-monitoring; and 3) enhancing
      internal motivation, self-efficacy, and self-management.

      All participants will undergo six monthly follow up, including data collection by using
      specific case record forms (CRF) and blood sample collection to check the blood glucose level
      using HbA1c and OGTT at alternate 6 month follow up visits. If the HbA1c value is more than
      6.5%, the participant is called for an OGTT. Participants who develop T2DM will not be
      followed up further. Participants who change glycaemic category but do not develop T2DM, as
      well as participants who continue in their glycaemic category, will be followed up.

      Control group participants will be referred to their usual doctor for ongoing management,
      with no attempt made to influence this. Any abnormal OGTT results during follow up will be
      provided to the patient and their doctor. This is entirely consistent with current usual
      care.

      Primary outcome: Proportion of women with change of glycaemic category, at or prior to final
      visit; from Normal Glucose Tolerance to Impaired Fasting Glucose (IFG) or Impaired Glucose
      Tolerance (IGT) or T2DM; or Impaired Fasting Glucose (IFG) or Impaired Glucose Tolerance
      (IGT) to Type 2 Diabetes Mellitus (T2DM).

      Secondary outcomes: Mean change in fasting blood glucose, mean change in body weight ,mean
      change in waist circumference (cm), changes in mean systolic blood pressure (SBP),mean change
      in physical activity level , change in diet.

      Data collection methods: Data will be collected at randomization and 6 monthly intervals
      thereafter, involving a brief case record form, with additional OGTT and HbA1c tests,
      alternately conducted at the follow up 6 monthly visits and both tests at the End of Study
      visit. Data will be captured electronically and data management will strictly comply with
      International Conference on Harmonisation - Good Clinical Practice (ICH-GCP) guidelines,
      utilizing Standard Operating Procedures established at participating institutes. Monitoring
      will be used to ensure quality and completeness of data, with an emphasis on central
      statistical monitoring to minimize costs.

      Data Analysis plan: Analysis will be based on the principle of intention-to-treat. The
      effectiveness of the study intervention on the primary outcomes will be determined using Cox
      models for survival data, with censoring of participants who develop a subsequent pregnancy
      or type 2 DM during follow-up. Analyses of secondary outcomes will be conducted using
      standard statistical procedures applicable to dichotomous, categorical or continuous data as
      appropriate. However, any country level change detected during the analyses will be reported.

      Research Ethics Approval: Ethics approval has been obtained from a number of ethics
      committees, including the University of Sydney Human Research Ethics Committee. In India,
      approvals from the Health Ministry Screening Committee and the All India Institute of Medical
      Sciences (Central Coordinating Centre) have been obtained as have approvals from each
      participating hospital. In Sri Lanka, approval has been obtained from the Ethics Review
      Committee, Faculty of Medicine, University of Kelaniya, which is accredited by the Ministry
      of Health. In Bangladesh, ethics committee approval from icddr,b has been obtained to allow
      involvement of all hospitals. The trial is registered with the Clinical Trials Registries of
      India and Sri Lanka.

      Consent: Participants willing to take part in the study will be consented by trial centres
      using a two-stage consent process with written informed consent being obtained both at
      initial engagement during pregnancy, as well as prior to randomisation. Participants will be
      given adequate explanation about the study and will be given ample time to consider their
      trial participation. They will be given the opportunity to ask questions about the trial and
      what their participation involves, and will receive clarification from the investigator and
      other study staff. A written informed consent form (using appropriately translated versions
      where appropriate) will be signed and personally dated by the subject or by the subject's
      legally acceptable representative, and by the person who conducted the informed consent
      discussion. If a subject is unable to read or if a legally acceptable representative is
      unable to read, an impartial witness should be present during the entire informed consent
      discussion and must attest the written informed consent form. A copy of the signed written
      informed consent form will be given to the trial participant.

      Donor: The study is funded under Global Alliance for Chronic Diseases (GACD) Grant
      (APP1093171) by National Health and Medical Research Council of Australia (NHMRC) and Indian
      Council of Medical Research (ICMR) GACD Grant.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Proportion of women with a change of glycaemic category, at or prior to final visit
time frame: 3 years
description: From Normal Glucose Tolerance to Impaired Fasting Glucose (IFG) or Impaired Glucose Tolerance (IGT) or T2DM; or Impaired Fasting Glucose (IFG) or Impaired Glucose Tolerance (IGT) to Type 2 Diabetes Mellitus (T2DM).
measure: Changes in fasting blood glucose as assessed by OGTT
time frame: 3 years
description: Mean Change in fasting blood glucose status during the study period among the respondents
measure: Change in body weight as assessed by the standard study weighing scale
time frame: 3 years
description: Mean change in body weight during the study period among the respondents.
measure: Change in waist circumference (in cm) as assessed by the standard study measuring tape
time frame: 3 years
description: Mean change in waist circumference (in cm) during the study period among the respondents.
measure: Change in systolic blood pressure (SBP) as assessed by Omron BP measuring machine
time frame: 3 years
description: Changes in mean systolic blood pressure (SBP) during the study period among the respondents.
measure: Change in physical activity level as assessed by Modified Global Physical Activity Questionnaire (MGPAQ)
time frame: 3 years
description: Mean change in physical activity level during the study period among the respondents.
measure: Change in dietary habits as assessed by Intake 24 (a 24-hour recall questionnaire)
time frame: 3 years
description: Mean change in dietary practice during the study period among the respondents.
arm group label: Intervention
arm group type: Experimental
description: Participants randomized in to the intervention group will receive group sessions, monthly phone calls, and telephonic prompts (text/voice recording).
arm group label: Control
arm group type: No Intervention
description: Control group participants will be referred to their usual doctor for ongoing management, with no attempt made to influence this. They will not get any part of the intervention but will receive the usual care (if any exists). Any abnormal OGTT results during the follow-up visits will be provided to the patient and their doctor. This is entirely consistent with current usual care.
intervention type: Behavioral
intervention name: Life style Intervention
description: The intervention will include 4 face-to-face group sessions in the first 6 months, followed by remote support strategies and intensification counseling sessions when needed. Ongoing support and contact shown to be important in supporting behavior change will consist of reminders, and motivational messages for small actionable behaviors, delivered using mobile text or voice messages. Program intensification will be offered to women who fail to meet their weight goals by the 6 month time point. All phases of the program focus on self- management across 3 themes
simple healthy eating and moderate physical activity messages;
behavioral skills such as problem solving/goal setting/self-monitoring; and
enhancing internal motivation, self-efficacy and self-management. The program is deliberately not prescriptive, and has a focus on sustainable behaviors and local context.
arm group label: Intervention
criteria: 
gender: Female
gender based: Yes
gender description: Participants must be women
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Anushka Patel, Ph.D
role: Principal Investigator
affiliation: The George Institute
last name: Nikhil Tandon, Ph.D.
role: Principal Investigator
affiliation: All India Institute of Medical Sciences, New Delhi
facility: 
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country: Bangladesh
country: India
country: Sri Lanka
citation: Gupta Y, Kapoor D, Josyula LK, Praveen D, Naheed A, Desai AK, Pathmeswaran A, de Silva HA, Lombard CB, Shamsul Alam D, Prabhakaran D, Teede HJ, Billot L, Bhatla N, Joshi R, Zoungas S, Jan S, Patel A, Tandon N. A lifestyle intervention programme for the prevention of Type 2 diabetes mellitus among South Asian women with gestational diabetes mellitus [LIVING study]: protocol for a randomized trial. Diabet Med. 2019 Feb;36(2):243-251. doi: 10.1111/dme.13850. Epub 2018 Nov 29.
PMID: 30368898
citation: Tewari A, Praveen D, Madhira P, Josyula LK, Joshi R, Kokku SB, Garg V, Rawal I, Chopra K, Chakma N, Ahmed S, Pathmeswaran A, Godamunne P, Lata AS, Sahay R, Patel T, Gupta Y, Tandon N, Naheed A, Patel A, Kapoor D. Feasibility of a Lifestyle Intervention Program for Prevention of Diabetes Among Women With Prior Gestational Diabetes Mellitus (LIVING Study) in South Asia: A Formative Research Study. Front Glob Womens Health. 2020 Nov 27;1:587607. doi: 10.3389/fgwh.2020.587607. eCollection 2020.
PMID: 34816163
citation: Shanthosh J, Kapoor D, Josyula LK, Patel A, Gupta Y, Tandon N, Jan S, Teede HJ, Desai A, Joshi R, Praveen D. Lifestyle InterVention IN Gestational diabetes (LIVING) in India, Bangladesh and Sri Lanka: protocol for process evaluation of a randomised controlled trial. BMJ Open. 2020 Dec 13;10(12):e037774. doi: 10.1136/bmjopen-2020-037774.
PMID: 33318108
responsible party type: Sponsor
mesh term: Diabetes, Gestational
mesh term: Pregnancy in Diabetics
mesh term: Diabetes Mellitus
sharing ipd: Yes
ipd description: To be developed
ipd time frame: To be determined
ipd access criteria: To de determined