Lifestyle Intervention IN Gestational Diabetes (LIVING)
Condition: Gestational Diabetes Mellitus in Pregnancy
MeSH terms: Diabetes, Gestational; Pregnancy in Diabetics; Diabetes Mellitus
Study type: Interventional

Summary: 
      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).
    

Detailed description: 
      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.
    

Intervention name(s): Life style Intervention
Intervention type(s): Behavioral
Intervention description(s): 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.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Gestational Diabetes,Lifestyle,Type 2 DM