Ectopic Fat in Singaporean Women - the Culprit Leading to Gestational Diabetes, Metabolic Syndrome, and Type 2 Diabetes (TANGO Study)
Condition: Non-Alcoholic Fatty Liver Disease
MeSH terms: Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Diabetes, Gestational; Metabolic Syndrome
Study type: Interventional

Summary: 
      Ectopic fat is the accumulation of adipose tissue in anatomical sites not classically
      associated with fat storage - for example, in the liver and skeletal muscles. Excessive fat
      accumulation in liver cells, often diagnosed as non-alcoholic fatty liver disease (NAFLD), is
      a precursor to a wide range of liver conditions and metabolic disorders. The usual standard
      of care for NAFLD is to advise weight loss through controlled diet and physical activity, but
      the outcome of weight management and treatment of NAFLD is highly variable.

      Diet interventions - such as the Mediterranean, ketogenic, paleo, and
      high-protein-low-carbohydrate diets - have shown varied benefits in the management of NAFLD.
      However, food-based interventions must align with cultural and regional preferences in food
      to succeed in making the modifications part of the habitual diet. A recent diet intervention
      study (Della Pepa et al., 2020) highlighted that the components of a diet, rather than its
      caloric content, play a greater role in achieving healthier outcomes. In this study, a
      multifactorial diet intervention using locally sourced and produced meals will be implemented
      with the aim of reducing elevated liver fat content in healthy women diagnosed with NAFLD.

      The study will also evaluate the effects of the proposed diet on the participants' metabolic
      health and describe potential changes in their gut microbiome signatures (via frequent stool
      samples). The dysregulation of the gut microbiota has been linked to the development of NAFLD
      and it is known that the composition of the gut microbiota could be modified by dietary
      intake. This study will investigate the association of gut microbiome signatures with
      elevated liver fat in Asian women and test whether the dietary intervention will modify their
      gut microbiota.

      Finally, ectopic fat in the liver is a highly prevalent condition worldwide but the cut-off
      values for NAFLD has been largely derived from studies performed in Western populations. This
      study seeks to cross examine the diagnostic ranges in various clinical assessments of NAFLD
      that commonly involve ultrasound spectroscopy (Fibroscan), fatty liver indexes (FLI) and
      magnetic resonance spectroscopy (MRS). This effort seeks to derive appropriate cut-off values
      for NAFLD in Singaporean-Chinese women.
    

Detailed description: 
      The study will consist of a 12-week, parallel three-arm, single-centre, randomized controlled
      trial (RCT); 90 women of Chinese ethnicity matched for age and BMI will be randomized to one
      of 3 study arms in 1:1:1 ratio by Blockrand R software at Week -1 visit. The study arms are:
      (1) Lifestyle advice alone, (2) Lifestyle advice with calorie-restricted diet-intervention,
      and (3) Lifestyle advice with calorie-restricted diet-intervention inclusive of odd-chain
      fatty acids (OCFA)-containing food product.

      In all 3 study arms, the lifestyle advice on maintaining a healthy diet and regular exercise
      (~180 mins/ week) will be compatible with recommendations by Health Promotion Board. The
      participants in the control study arm (Lifestyle advice alone) will receive 1 session of diet
      advice from the study dietician at the start of the study only. The dietitian will provide
      dietary advice on the eating plans and instructions for completion of diet checklist.

      In the "Diet Intervention (calorie-restricted multifactorial diet)" study arm (arm 2), a
      moderate energy restriction (500-1000 kcal/day) will be prescribed to facilitate weight loss.
      To facilitate compliance, participants in the diet-intervention arms will receive individual
      diet consultations with the study dietitian during the study. Participants in both the
      meal-based diet-intervention arms (arm 2 and arm 3) will be supplied with 2 main meals per
      day as part of their daily diet, for 6 days a week. Additional food products may be supplied
      for breakfast and snacks. The diet will be designed to be nutritionally replete, feasible,
      and sustainable in the long-term. The diet will be based on whole grain-based products,
      vegetables, legumes, extra virgin olive oil, fruits, almonds, salmon, and plant-based meat
      analogues. Diet plans will be individualized and energy matched to enable any metabolic
      differences between arms to be attributed to the macronutrient profiles of the diets, without
      confounding by differences in weight loss between diet arms. Energy requirements will be
      calculated by indirect calorimetry (Quark CPET, COSMED) with an activity factor.

      Participants in the "OCFA meal-based diet-intervention" study arm (arm 3) will be provided
      with a daily OCFA-containing food product, in addition to the lunch and dinner meals. Both
      the participants in arm 2 and 3 will be receiving the same lunch and dinner meals.
      Participants in both the meal-based diet-intervention arms (arm 2 and arm 3) will be told to
      consume only low-fat dairy products (milk, yoghurt), avoid ruminant meat (beef, lamb), avoid
      cheese, butter and butter-containing food products. Both diet-intervention arms will be told
      to avoid sugar-sweetened beverages.
    

Intervention name(s): Lifestyle Advice; Diet Intervention; OCFA Meal-Based Diet-Intervention
Intervention type(s): Other; Other; Other
Intervention description(s): Maintain a weekly healthy diet and regular exercise.; Calorie-restricted meals (lunch and dinner); OCFA-containing food product
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Other