Effects of Divalproex Sodium on Food Intake, Energy Expenditure, and Posture Allocation
Condition: Healthy
Intervention: divalproex sodium
Intervention description: Divalproex sodium vs. placebo
Intervention MeSH terms: Valproic Acid
Phase: Phase 4
Study type: Interventional
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 57.0
Sex: All
Minimum age: 18 Years
Maximum age: 54 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: divalproex sodium; valproic acid; food intake; energy expenditure; posture allocation; None, the population of study is healthy

Summary:

      The purpose of the proposed study is to identify the mechanisms responsible for the weight
      gain associated with Depakote treatment, and to identify methods to prevent and treat weight
      gain in people taking Depakote. Both sides of the energy balance equation will be measured in
      a sample of healthy lean and overweight adults. Energy intake will be measured in the
      Pennington Center's Eating Laboratory, and total daily energy expenditure (TEE) and posture
      allocation will be measured with the IDEEA™. Questionnaires that assess food cravings and
      eating attitudes and behaviors will be used to determine if a behavioral phenotype is
      associated with weight gain in response to Depakote treatment. It is hypothesized that
      Depakote treatment will result in increased food intake. It is also hypothesized that the
      time spent engaging in sedentary behavior will increase in response to Depakote treatment.
      Time spent engaging in, and the energy expended during, physical activity is expected to
      decrease significantly. Therefore, it is hypothesized that TEE is expected to decrease
      significantly. The results will be used to identify specific behavioral targets to prevent
      weight gain during treatment with Depakote. Potential targets include interventions to modify
      food intake and physical activity. The degree to which each behavior (food intake or physical
      activity) will be targeted is dependent on the results of this study. For instance, if the
      majority of the weight gain associated with Depakote treatment is due to changes in food
      intake, stronger dietary interventions will be suggested. Additionally, changes in endocrine
      factors (hormones and peptides) will be evaluated during the study to determine if Depakote
      is associated with an altered endocrine response that affects satiety, food intake, or energy
      expenditure. If an altered endocrine response is found, these results will be used to
      identify adjunctive medications or compounds to correct the endocrine response and reduce
      weight gain. Genomic studies will also be possible, since gene sequencing and gene expression
      can be analyzed from archived buffy coat samples.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Healthy male or female, age 18 to 54 years

          2. 20 < Body Mass Index (BMI, kg/m2) < 30

          3. Willing to have a blood sample stored for possible future genetic testing

        Exclusion Criteria:

          1. For females, pregnant or unwilling to use an effective form of contraception while on
             this study (hormonal methods like birth control pills, implants or shots; barrier
             methods like condoms or diaphragms with foam; surgical sterilization; or abstinence)

          2. For females, use of any other oral contraceptive other than monophasic oral
             contraceptives

          3. For females, irregular menstrual cycles

          4. For females, history of partial hysterectomy

          5. For females, nursing

          6. For females, history of polycystic ovarian syndrome

          7. Aspirin use or the refusal to abstain from aspirin use during the study

          8. Current or history of urea cycle disorders

          9. Tobacco users

         10. Use of anti-convulsant medication

         11. Use of barbiturates, such as Phenobarbital

         12. Use of tranquilizers, such as Xanax and Valium

         13. Use of blood thinners, such as Coumadin

         14. Use of anti-depressant medication

         15. Liver disease or impaired liver function

         16. History of pancreatitis

         17. Regular (4 or more days per week) consumption of 3 or more alcoholic beverages a day

         18. Refusal to abstain from alcohol intake during the study

         19. Dietary restraint score > 14 or disinhibition score > 12 on the Eating Inventory [19]

         20. Dislike or allergy to the food used during the food intake tests

         21. Unwilling to wear an IDEEA™ during the study

         22. Unwilling to wear an accelerometer during the study