The study is a controlled randomized parallel group 40-week trial to compare the intermediate-term weight-loss efficacy of two patterns of prescribed calorie restriction using a soy-based meal replacement product. Subjects were randomly assigned to a sequence of either 12 weeks at 1200 kcal/day, 16 weeks at 1500 kcal/d and 12 weeks at 1800 kcal/d (the 12/15/18 diet group), or 28 weeks at 1500 kcal/d and 12 weeks at 1800 kcal/d (the 15/18 diet group). Secondary outcomes were body fat, waist circumference, serum lipid concentrations and blood pressure.
Overweight/obese persons with body mass index (BMI; kg/m2) between 28 and 41 (men: n = 13 and women: n = 86) between the ages of 35 and 65 were enrolled in this trial. Exclusion criteria were: weight loss >5 kg in the past 3 months, use of weight loss medication within the past 6 weeks, scores above the 90th percentile on the Brief Symptom Inventory (BSI, a screening measure of general psychological functioning), presence of disease not believed to be at least partially the result of obesity and treatable by weight reduction, medical or psychological contraindications as determined by study investigators, or known hypersensitivity to any of the ingredients of the formula, including but not limited to, soy protein. The study was approved by the IRB at St. Luke's/Roosevelt Hospital, and all subjects provided written informed consent. Prior to participation and acceptance into the program, subjects were deemed medically fit for safe weight loss through a physical examination. After meeting eligibility criteria, candidates were randomized via computer-generated pseudo random numbers at a 1:1 allocation ratio, without regard to race or sex, to one of two treatment groups described below. Thirty-seven subjects enrolled in this trial had formerly been the control group for a 12-week weight loss study which has been described elsewhere . An additional 62 were newly recruited from clinic records and advertisements in the local press.
Ninety-nine subjects were randomized, 50 into the 12/15/18 treatment group and 49 into the 15/18 treatment group. Sixty-one subjects remained after 12 weeks, 42 after 24 weeks, and 30 subjects completed the 40-week trial.
All subjects received the Scan Diet meal-replacement formula, instructions for its use, a single session of dietary counseling and a pamphlet describing healthy weight loss practices. The 12/15/18 treatment group was instructed to begin with a 1200 kcal daily diet that consisted of 5 Scan Diet Shakes, 4 exchanges of fruit, 4 exchanges of vegetables and 1 fat exchange. They were given a copy of the Nutricia Scan Diet Meal Plan booklet, describing the diet, as well as a copy of The American Dietetic Association's booklet "Exchange Lists for Weight Management." After 12 weeks the diet instruction was changed to 1500 kcal daily consisting of 3 Scan Diet Shakes, 5 carbohydrate exchanges, 7 exchanges of fruit and vegetables, 5 meat exchanges and 2 fat exchanges. After 16 weeks the diet was increased to an 1,800 kcal/d made up of 2 Scan Diet Shakes, 2 milk, 9 carbohydrate, 8 fruit and vegetable, 8 meat and 3 fat exchanges. The 15/18 group began their weight loss program at the 1500 kcal/day level and was instructed to follow it for 28 weeks. After 28 weeks the diet was increased to the 1800 kcal/d level, as described above, for the final 12 weeks.
Throughout the study, subjects made visits to the clinic at 4 week intervals. At each visit, subjects were checked for compliance and supplied with sufficient meal replacement formula to last until the next scheduled visit, plus one additional week. At each visit anthropometric measures, blood pressure, and psychological wellness assessments were obtained. Blood samples for laboratory assessment included standard blood work at initial screening (i.e., complete blood count and serum lipids) and lipids and serum at weeks 4, 8, 12, 16, 24, 32 and 40. Samples were analyzed by a commercial lab (Quest Diagnostics, Teterboro, NJ). Body weight was measured within 0.1 kg using a standardized calibrated scale. Height was measured within .10 cm using a wall-mounted stadiometer. Body fat was measured through the use of a TANITA bio-impedance analyzer (TBF 305) and waist circumference was taken with a non-distensible tape measure according to published guidelines [11, 12]. Blood pressure was measured after at least 5 minutes rest using a standard mercury sphygmomanometer and appropriately sized cuffs according to the guidelines of the American Heart Association. Side effects and adverse events were assessed by a standardized interview/questionnaire, the Monitoring of Side Effects Scale . The 70-items are answered on a 5-point scale ranging from 0 = not present to 4 = severe.
The principal aim of the analysis was to compare the effects of the two diet prescriptions over time on the primary and secondary outcomes. We also investigated possible differences in treatment response by the subjects who had been the control group in a previous study with the response of newly recruited subjects.
In initial exploratory analyses, we used two-sample independent t-tests to compare changes from baseline between the two treatment groups at each follow-up visit for, first, only newly recruited subjects and, second, for all subjects. This analysis was used to determine if differences between groups were more apparent for newly recruited subjects. T-tests were also used to assess changes from baseline at each follow-up visit. In this latter analysis, the two treatment groups were combined but separate analyses were run for subjects obtained from our short-term trial [, referred to as Study 1], newly recruited subjects, and all subjects together.
We also employed mixed effects regression models with subject as a random effect. This technique accommodated the evaluation of multiple terms in a single model, the evaluation of potentially significant interaction terms, and missing data due to drop-out . These mixed effects models were computed for changes in weight, body fat, waist circumference, total cholesterol (TC), low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), the proportion of TC as HDL (i.e., HDL/TC), triglycerides, and systolic and diastolic blood pressure.
A typical model was of the form,
= β0 + β1(Time
) + β2(Time
)2 + β3(Base
) + β4(GRP
) + β5(IN1
) + S
where the j subscript denotes a follow-up visit, the i subscript denotes subject, and Y
, the dependent variable is the change from baseline (e.g., follow-up weight – baseline weight), Time is the number of weeks since the initial baseline visit, Base is the baseline value of the outcome variable, GRP= 1 for subjects in the 15/18 group and zero for the 12/15/18 group, IN1 = 1 for subjects who participated in the initial study and 0 for newly recruited subjects, S is a random effect term for each subject assumed to have a zero mean and variance
, ε represents random errors assumed to be normally distributed with mean zero, variance σ2, and is assumed to be independent of S. Time was coded as a numeric quantity which allowed the development of a functional relationship between Time and change from baseline. Once a model is selected and fitted to the data for a particular outcome variable, the interrelationships between GRP, Time, Base, and IN1 were assessed.