Puberty Related Intervention to Improve Metabolic Outcomes (The PRIMO Study)
Condition: Obesity
MeSH terms: Obesity
Study type: Interventional

Summary: 
      Puberty represents a critical period in terms of metabolic health. Racial differences in
      insulin dynamics, reproductive maturation, and the associated endocrine changes may affect a
      female's health later in life. Further, the peripubertal period is likely the period of
      racial divergence in adiposity noted between European American (EA) and African American (AA)
      girls. Diet is a major modifiable risk factor. The identification of simple, cost-effective
      dietary strategies for prevention and management of metabolic disease and excess fat mass
      accrual during the peripubertal period is a priority. Modification of the diet to affect
      metabolic and endocrine outcomes with and without weight loss during the pubertal transition
      represents a novel approach to the pediatric obesity epidemic.

      It is likely that the two diets used in this project will have different metabolic effects,
      including effects on postprandial glycemia, triglyceride concentration, free fatty acid
      concentration, and satiety. These factors may in turn, affect development of metabolic
      perturbations, especially in susceptible individuals (e.g. AA peripubertal girls).The role of
      carbohydrates on metabolic outcomes, particularly among children, has received little
      attention. It has been hypothesized that higher postprandial glycemia may be a mechanism for
      disease progression. Development of a diet that reduces insulin secretion and optimizes
      metabolic-endocrine health among peripubertal girls will likely reduce obesity and related
      co-morbidities and future reliance on pharmacologic treatments, even in the absence of weight
      loss. However, in light of the current trends in pediatric obesity, a safe and effective
      regimen that also promotes weight loss is needed for the pediatric population.

      This proposal is significant in that it will shed light on whether diet composition, as a
      part of a eucaloric (weight-stable) or hypocaloric diet (weight-loss) can influence the
      hyperinsulinemic characteristic of AA peripubertal girls. Existing data suggest that elevated
      concentrations of insulin and/or reproductive hormones may contribute to the fat mass accrual
      in AA and could elevate risks for development of chronic diseases in adulthood. The results
      of this study will lead to the development of dietary means for the reduction of insulin, and
      thereby to the prevention of both pediatric obesity and type 2 diabetes.
    

Detailed description: 
      This study will include 100 European and African American girls ages 7-11 years. Subjects
      must be non-diabetic and overweight (percentile BMI >85th ).

      Screening First they will complete a telephone questionnaire regarding medical history and
      current lifestyle (approximately 15 minutes). If the subject is deemed eligible based on the
      telephone screening, they will come to UAB for an orientation meeting. At this time the
      subjects' height and weight will be recorded. They will receive a copy of the study
      assent/consent form and review the entire protocol with selected study personnel
      (approximately 60 minutes).

      Protocol

      Run-In Phase With parental guidance, subjects will complete a 4-day food record for
      assessment of typical nutrient intake (attached) prior to beginning the run-in diet. The
      4-day food record will be analyzed by a registered dietitian using the Minnesota Nutrition
      Data System. Then subjects will be provided food for 3 days. This diet is similar to the
      standard "American" diet, and is intended to eliminate inter-subject variance in metabolic
      outcomes due to free-living dietary factors. The total energy of all diets will be calculated
      to be eucaloric so that body weight is maintained, and will be determined using the
      Harris-Benedict equation with an activity factor of 1.35. In previous and ongoing studies at
      the UAB CRU, this method has resulted in maintenance of body mass. Subjects will come to UAB
      to be weighed and pick up meals. All meals will be packaged for home consumption. Upon
      completion of the Run-in Phase, subjects will report to the CRU Outpatient facilities for
      metabolic testing and WEBB and Boshell buildings for body composition assessment. The tests
      administered are described below.

      Phase 1 Weeks 1-6. Subjects will be randomized to a controlled eucaloric reduced-CHO (SPEC)
      or a controlled eucaloric standard (STAN) diet. Subjects will come to UAB two days a week in
      the morning (Monday-Friday) to be weighed and to collect food for their meals. Energy needs
      will be estimated by a qualified dietitian using standard equations. All foods for the diet
      intervention will be provided by the study. Body weight will be recorded to ensure weight
      maintenance. Energy intake will be adjusted if necessary to maintain body weight. Upon
      completion, subjects will report to the CRU Outpatient facilities for metabolic testing and
      WEBB building for body composition assessment. The tests administered are described in the
      chart below.

      One morning, approximately at the midpoint of phase 1, subjects will be asked to come to the
      CRU and undergo a solid meal test. This test will measure the hormonal and glycemic response
      to consuming a breakfast that will be provided as a part of the study. The details of this
      test are outlined below.

      Phase 2 Weeks 7-18. Subjects will continue in their assigned diet groups (i.e. SPEC or STAN),
      but will now receive a controlled hypocaloric diet designed to facilitate weight loss.
      Subjects will report to UAB two weekday mornings to be weighed and to collect food for their
      meals. Energy needs will be estimated by a qualified dietitian. All foods for the diet
      intervention will be provided by the study. Body weight will be recorded two times weekly to
      monitor weight loss. Upon completion of phase 2, subjects will report to the CRU Outpatient
      facilities for metabolic testing and the WEBB building for body composition assessment. The
      tests administered are described in the chart below.

      Education and Counseling Sessions At the time of completion of Phase 2, study participants
      will initiate a series of education and counseling sessions designed to allow them to
      continue with their assigned diets under a free-living situation for the ensuing 6 weeks. The
      goal of this phase will be maintenance of the weight loss that occurred during the formal
      intervention. Subjects will attend group meetings during the 6-week follow-up phase. These
      meetings will occur weekly during weeks 19-22, and bi-weekly during weeks 23-25. The periodic
      education and counseling sessions will serve to reinforce the diet guidelines, and to
      evaluate any problems that have arisen.

      Phase 3 Weeks 19-25 subjects will be in a "free-living phase." During weeks 19-25, a
      dietitian will periodically administer unannounced 24-hour diet recalls by telephone. This
      involves subjects reporting foods they consumed during the previous day. At the end of Phase
      3 subjects will receive a DXA scan and have resting energy expenditure assessed.
    

Intervention name(s): Macronutrient Modification
Intervention type(s): Other
Intervention description(s): reduced carbohydrate versus standard carbohydrate diet
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Prevention
Keywords: puberty; body composition; metabolism; obesity; optimization of body composition; pubertal transition