The Effect of Intermittent Energy Restriction Using Meal Replacements in Overweight Chinese Subjects
Condition: Obesity; Fasting
MeSH terms: Overweight
Study type: Interventional

Summary: 
      Background and Aims: The "5:2 diet", a form of intermittent energy restriction, has been
      popularized in Europe and USA. The rationale behind this approach is that two days of dieting
      is potentially more achievable, yet long enough to reduce overall weekly energy intake.
      However, this specific approach is lacking in evidence. Therefore, we are keen to investigate
      the effectiveness of this form of intermittent energy restriction compared with a control
      intervention (providing dietary and exercise advice only), in overweight, Chinese subjects,
      for an intervention period of 12 weeks.

      Design and Methods: This will be a randomized controlled trial, with 15 subjects in each arm,
      for an intervention period of 12 weeks. Subjects randomized to the treatment group will take
      three packets of a meal replacement product (Optifast®) per day during two consecutive
      fasting days, and take a healthy balanced diet that meet estimated energy requirements for
      the remaining five days. Subjects randomized to the control group will be given general diet
      advice and allowed to eat ad libitum throughout the study period. Measurements and laboratory
      tests will be done at baseline, 4 weeks and 12 weeks. Adherence to the dietary interventions
      will be assessed at 4 weeks and 12 weeks using 7-day food diaries.

      Significance: This will be the first study looking at an Asian population and will serve as a
      pilot towards a larger randomized trial. If this approach is found to be safe, effective and
      easier to adhere compared to the traditional continuous energy restriction, then it will be a
      very valuable option in the treatment of obesity, which has become an increasing problem
      globally including Singapore.
    

Detailed description: 
      1. STUDY DESIGN This will be a single centre, randomized controlled trial (RCT), comparing
           the intervention in question (Intermittent Energy Restriction (IER), "5:2 diet",
           treatment: 2 consecutive days of fasting (using meal replacement, Optifast®) per week)
           with a control of "advice only", with 15 participants in each arm, in an adult
           overweight, Chinese sample, for an intervention period of 12 weeks. Each potential
           participant will be subjected to a pre-study assessment and a trial of 2 consecutive
           fasting days with Optifast® as per intervention. Potential participants will be formally
           enrolled into the study if they successfully tolerated the 2 consecutive fasting days
           with no contraindications to participation. The actual study period is 12 weeks,
           consisting of 4 study visits and 3 telephone calls between the study visits.

           This study design with a control arm (and randomisation) would provide more conclusive
           evidence if there is a significant difference between the two groups at the end of the
           study, with the difference most likely attributed to the intervention (IER, "5:2 diet",
           treatment).

        2. METHODS AND ASSESSMENTS

      2.1. Randomisation and Blinding Eligible subjects will be randomised to two groups: the
      intervention group and the control group. This will be achieved using an online randomisation
      plan generator (www.randomization.com), with the plan generated by the Clinical Research Unit
      in Khoo Teck Puat Hospital (KTPH). Assignment will be contained within opaque sealed
      envelopes, and opened only in the presence of the investigator and the subject.

      With regards to blinding, only personnel performing laboratory measurements will be blinded
      to the group allocation of the subjects. The rest of the study personnel, including the
      research nurse taking the anthropometric measurements, will not be blinded.

      2.2. Contraception and Pregnancy Testing Females of childbearing age included in the trial
      will be discouraged from getting pregnant during the study period, but contraception will not
      be strictly enforced. However, if any participant is found to be pregnant or might be
      pregnant during the course of the study, she will be withdrawn from the study in view of the
      nutritional demands of pregnancy.

      2.3. Study Visits and Procedures

        1. Pre-study trial and procedures Interested participants will be assessed for their
           suitability for the study including physical and psychological health, and their
           motivation to lose weight. Those who continue to be eligible will be given a trial of 2
           consecutive fasting days with Optifast® as per intervention in this study. Those who
           successfully completed this trial and still express interest in this study will be
           formally recruited into the study, and the first study visit will then be arranged.

        2. Week 0: Study Visit 1 Measurements (height, weight, waist circumference, hip
           circumference, %body fat by bio-electrical impedance analysis, blood pressure) and
           laboratory tests (Fasting Lipids, Fasting Glucose, Fasting Insulin, Liver panel, Full
           Blood Count, B-hydroxybutyrate) will be done during this visit. Quality Of Life (QOL)
           will be assessed using the RAND Short Form (SF)-36 health survey during this visit.

        3. Week 4: Study Visit 2

           Measurements (height, weight, waist circumference, hip circumference, %body fat by
           bio-electrical impedance analysis, blood pressure) and laboratory tests (Fasting Lipids,
           Fasting Glucose, Fasting Insulin, Liver panel, Full Blood Count, B-hydroxybutyrate) will
           be done during this visit. Adherence to the dietary interventions will be assessed based
           on 7-day food diaries done prior to study visit.

        4. Week 8: Study Visit 3

           Only measurements (height, weight, waist circumference, hip circumference, %body fat by
           bio-electrical impedance analysis, blood pressure) will be done during this visit.

        5. Weeks 2, 6 and 10: Telephone Call

           Subjects will be contacted via telephone to reinforce compliance to study protocol and
           asked for any adverse effects during these calls.

        6. Week 12: Final Study Visit Measurements (height, weight, waist circumference, hip
           circumference, %body fat by bio-electrical impedance analysis, blood pressure) and
           laboratory tests (Fasting Lipids, Fasting Glucose, Fasting Insulin, Liver panel, Full
           Blood Count, B-hydroxybutyrate) will be done during this visit. Adherence to the dietary
           interventions will be assessed based on 7-day food diaries done prior to study visit.
           QOL will be assessed using the RAND Short Form-36 health survey.

        7. Discontinuation Visit and Procedures Participants may withdraw voluntarily from
           participation in the study at any time. If this occurs, the reason to withdraw will be
           documented and participants will be offered other obesity treatment options in Health
           For Life Centre (HFLC), KTPH. Subjects who accept other treatment options will be
           managed accordingly like usual patients treated in HFLC, KTPH and there will be no
           further trial procedures for these subjects. However, if subjects no longer wish to
           embark on a weight loss journey, they will be advised to continue scheduled evaluations
           as per protocol as far as possible to facilitate an intention to treat analysis.
    

Intervention name(s): Meal Replacement
Intervention type(s): Dietary Supplement
Intervention description(s): Using a Meal Replacement product, supplemented by protein powder and multivitamin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment