The Healthy Diet and Lifestyle Study
Condition: Visceral Fat
Study type: Interventional

Summary: 
      This pilot study aims to develop a study design to test the difference between a fasting diet
      and a heart healthy diet, assess participants' adherence to the study design, and to test
      whether either diet helps to reduce fat wrapped around the organs in the stomach area and
      total body fat in East Asian American adults. 70 men and women residents of Oahu Hawai'i,
      aged 35-55, who are overweight or obese and have moderate to high amounts of fat around
      organs in the stomach area, of Japanese, Chinese, or Korean ancestry, will be equally
      distributed to either the fasting diet or the heart healthy diet and asked to follow this
      diet for the 12-week study. Each diet has set requirements for energy, protein,
      carbohydrates, and fat. The fasting diet has two days of fasting, where participants will be
      asked to follow a low carbohydrate- low energy diet, and five days of a balanced diet without
      any energy restriction (the Mediterranean diet). The other group will follow a heart healthy
      diet (Dietary Approaches to Stop Hypertension diet) for all seven days without any energy
      restriction. Both groups will be asked to follow a moderate exercise program (one hour of
      walking five days a week). Dietitians will provide information on diet and exercise
      requirements to the participants at the start of the study. Dietitians will contact the
      participants seven times, primarily by phone, to offer support and to check if the
      participants are following prescribed diet and exercise plans. Participants will use a mobile
      phone app to take images of all foods and drinks for four days at the beginning, middle and
      end of the 12-week study. Body measurements, including measurements of body fat, will be
      taken at the beginning and end of the study by trained clinic staff. The analysis of the food
      images, participants' self-reported compliance to diet and exercise plans, and body
      measurements will be used to determine if the study design and participant compliance to the
      study are successful, and to assess which diet is better at reducing total body fat and fat
      around the organs in the stomach region.
    

Detailed description: 
      Background and rationale: East Asian adults are known to have higher levels of visceral
      adiposity than whites, African Americans, and Hispanic adults in the US. This visceral fat
      deposition, because of its close proximity to the portal vein, has greater metabolic activity
      and is associated with a greater risk of cardiometabolic diseases and possibly certain
      cancers (e.g., breast and colorectal cancers). Newly introduced weight loss interventions,
      specifically, intermittent energy restriction (IER), have been proposed to be as effective as
      continuous energy restriction, achieve higher and long-term compliance, and may predominantly
      result in a decrease in visceral fat. Thus, implementing this novel weight loss intervention
      among East Asian Americans with high visceral fat deposition would be particularly beneficial
      .

      Goal: This study aims to demonstrate the feasibility to conduct an intermittent energy
      restriction (IER) nutritional intervention aimed at reducing visceral adiposity in overweight
      Asian Americans middle-aged adults.

        1. To finalize and implement a protocol for an IER intervention plus exercise with the goal
           of reducing visceral fat in overweight adult East Asian Americans (EAA). The protocol
           will include an intensive dietary intervention and an exercise program administered by a
           dietitian through individual meetings and the use of new technologies to monitor dietary
           compliance.

        2. After eligibility screening, 70 individuals will be randomized to either the intensive
           intervention diet group or to a non-intensive intervention (active comparator) diet
           group for 12 weeks. The intensive intervention group will follow a low carbohydrate- low
           energy IER diet for two consecutive days, and the Mediterranean (MED) diet for the other
           five days and meet estimated energy requirements (IER + MED group). The active
           comparator group will follow the Dietary Approaches to Stop Hypertension (DASH) diet for
           all seven days and meet estimated energy requirements (DASH group). With an expected
           attrition rate of ~25%, the investigators expect ~50 participants to complete the study.

        3. To evaluate study retention, protocol adherence, effect size of the intervention on body
           weight, total adiposity, DXA measured visceral fat (main outcome), estimated visceral
           adipose tissue area, and selected clinical measures (e.g., waist circumference, hip
           circumference).

      Design: Randomized lifestyle intervention trial to compare the effects of two twelve-week
      diets - (i) an IER + MED diet versus (ii) DASH diet- on DXA quantified visceral fat
      deposition distribution in overweight/obese men and women. Both intervention groups will be
      asked to follow a moderate exercise program (1 hour of walking five days a week). The
      research will be carried out in the University of Hawaii Cancer Center (UHCC). The
      investigators will determine and compare the primary and secondary endpoints at least five
      days after the last 2 energy-restricted days to a corresponding day of the week in the DASH
      group at the completion of the 12th week of IER+MED or DASH diets.

      Assessing dietary intervention adherence: Dietary intake of energy, fat (monounsaturated
      fatty acids (MUFA), Polyunsaturated fatty acids (PUFA) and saturated fat), carbohydrate,
      protein, dietary fiber and alcohol will be assessed prior to the first week of intervention,
      the 5-6th week, and the 12th week. Participants will capture images of foods eaten and
      consumed over four days (i.e., before and after images of each eating occasion). A mobile app
      designed to seamlessly take images of foods/beverages will be loaded to onto each
      participant's mobile telephones for free and removed at the end of the study. Physical
      activity level will be assessed at baseline using a physical activity questionnaire.

      Advice, support and monitoring in both diet groups Foods eaten for the IER+MED and DASH diets
      will be self-selected by the participants and not provided by the study team. The IER+MED and
      DASH groups will receive clear instructions on how to follow the allocated diet in a
      face-to-face dietary consultation with one of the trial dietitians (45- 60 minute
      appointment) at the UHCC. Both groups will receive comprehensive written instructions of how
      to follow the diets at home, including recommended portion sizes and recipes and suggested
      meal plans. Both groups will receive appropriate behavioral techniques to promote adherence
      to diets (i.e., self-monitoring of diet and goal setting).

      Participants will be contacted by telephone by an allocated dietitian one week after
      randomization to check that they have started the diet, to assess understanding of the diet
      and to provide any trouble shooting advice. Participants will be contacted by an allocated
      dietitian with weekly phone calls in weeks 1 to 4 to discuss adherence and any problems with
      the diet; and with every other week phone calls in weeks 5 to 12. Both groups will be asked
      to record 4-day dietary records with the mobile food record at Week 6 and Week 11. This will
      allow assessment to adherence of the allocated diets and better tailor dietary advice.
      Participants will be asked to report overall compliance to the diet and physical activity
      plans using a scale of 0-10 for each, on the weekly and fortnightly phone calls with the
      dietitian. The IER+MED group will also be asked to record adherence to the 2-day IER using a
      scale of 0-2. All participants will also be advised to become more active, walking at least
      one hour per day five days per week. The intermittent energy restriction (IER) group will be
      encouraged to walk on the non-IER days.

      Post-Study At the end of the study all participants will be offered advice on continued
      weight loss and/or weight loss maintenance if they have reached a target weight and this is
      appropriate. This will include advice regarding preferred diet, i.e., IER+MED or DASH. If
      resources permit, the investigators will recontact participants six and twelve months after
      the end of the intervention to assess dietary intake, physical activity and body weight.

      Statistical Considerations Statistical analysis will be conducted within Epidemiology
      Program, UHCC. The primary aim is to determine changes in percentage visceral fat between the
      IER+MED diet and the DASH diet over a 3 months period. The sample size of 25 participants per
      group has been chosen to detect a difference of 15 percentage points in the reduction in
      visceral fat between the two different diets, assuming an estimated 25% drop-out rate.
      Calculations assume a two-sided t-test with estimated standard deviation of 10% and the
      conventional 5% significance level. The primary analysis will be performed on an
      intent-to-treat principle, where all participants will be analyzed by randomization group,
      regardless of compliance.

      The primary endpoints of visceral fat measurements will be regressed on randomization group
      and time point, as well as potential confounders, using a mixed model approach accounting for
      the repeated measures at baseline, and 6 and 12 weeks. The primary hypothesis will be tested
      by a contrast F test comparing the difference between groups in the change from baseline to
      12 weeks. The 6 month assessment will be similarly tested to understand the trend over time.
      If there is evidence of a linear change in fat over time, time will be entered as a
      continuous variable and the slope will be compared between groups. Visceral fat will be
      modelled as an absolute area and as percentage of total area. The secondary analysis will
      analyze relationship between the IER+MED intervention and total adiposity.

      Ethical Considerations The study will be performed in accordance with the ethical principles
      in the Declaration of Helsinki and the University of Hawaii operational and ethical
      guidelines for research and other applicable regulatory requirements.

      Participant information and consent Consent to enter the study will be sought from each
      participant only after a full explanation has been given, information has been provided and
      time allowed for consideration. The right of the participant to refuse to participate without
      giving reasons will be respected.

      Discontinuation and withdrawal Participants are free to withdraw from the study at any time,
      without prejudice to further treatment. Participants may also be discontinued from the study
      at any time, at the discretion of the investigator. Requests by the participant to be
      withdrawn from the study should be made through the principal investigator.

      Confidentiality After the participant has consented, any information from the study will be
      stored on a secure password-protected computer that will be accessible only to the research
      team. Trial data on anthropometry and activity meter data will be kept in a secure computer
      at the UHCC. The food & beverage images from the 4-day mobile food records will be kept on a
      secure server.

      Data Handling and Record Keeping All data will be kept strictly confidential. Any individual
      volunteering to participate will be assigned a code number, with the link to identifying
      information only available to the few study staff that require this information. Identifying
      information will be maintained in separate secure computer files from the remainder of the
      data. All forms will be stored in locked file cabinets, and those with identifying
      information will be stored separately from the other forms. No analysis will ever identify
      participants individually.
    

Intervention name(s): IER+MED group; DASH group
Intervention type(s): Behavioral; Behavioral
Intervention description(s): Follow a Mediterranean diet 5 days per week and follow intermittent energy restriction 2 days per week.; Follow the distribution of macronutrients and food groups prescribed by the DASH diet 7 days per week.
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Randomized controlled trial. Participants will be randomized to either the IER+Med diet or the DASH diet for 12 weeks.
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: intermittent energy restriction; Randomized Controlled Trial; Adiposity