Interaction Between Drug and Placebo Effect:Randomized Placebo Controlled Trials May Not be Accurate in Determining Drug Effect Size
Condition: Placebo Effect; Placebo Drug Interaction
Study type: Interventional

Summary: 
      The total effect of a medication is the sum of its drug effect, placebo effect (meaning
      response of placebo), and their possible interaction. Current interpretation of the results
      of clinical trials (the gold standard in evidence based medicine) assumes no such
      interaction. Using a novel cross-over balanced placebo design and caffeine as a model drug,
      the investigators have recently shown that a negative interaction does exist; suggesting that
      the size of drug effect as currently measured by clinical trials may not be accurate. Due to
      the novelty of the findings and their important clinical practice and research implications,
      they need to be confirmed using another drug; and the size of drug effect measured using the
      novel design need to be directly compared to that measured using conventional clinical trial
      design. The results of the study are expected to further our understanding of a widely used
      medical intervention, i.e., placebo, and help assess the appropriateness of randomized
      clinical trials in determining the size of drug effect.
    

Detailed description: 
      BACKGROUND:

      The total effect of a medication is the sum of its drug effect, placebo effect (meaning
      response of placebo), and their possible interaction. Current interpretation of the results
      of clinical trials (the gold standard in evidence based medicine) assumes no such
      interaction. Using a novel cross-over balanced placebo design and caffeine as a model drug we
      have recently shown that a negative interaction does exist; suggesting that the size of drug
      effect as currently measured by clinical trials may not be accurate. Due to the novelty of
      the findings and their important clinical practice and research implications, they need to be
      confirmed using another drug; and the size of drug effect measured using the novel design
      need to be directly compared to that measured using conventional clinical trial design.

      DESIGN:

      A cross-over balanced placebo plus randomized placebo-controlled clinical trial design.

      METHODS:

      480 adults will be double-blindly randomized to three groups: first generation H-1 receptor
      antagonist- hydroxyzine (25 mg), placebo, or hydroxyzine+placebo group. The first two groups
      will receive the assigned intervention described by the investigators as hydroxyzine or
      placebo, in a randomized crossover design. The third group will receive hydroxyzine and
      placebo in a randomized double-blind placebo-controled crossover design. Group assignment
      will be concealed from volunteers and recruiters. Data collectors will be blinded to group
      assignment and intervention assignment. Volunteers will be partially deceived to the
      intervention assignment in the first two groups and blinded in the third group. The
      interventions to the third group will be also administered blindly. Serum hydroxyzine levels
      will be determined 3 hours post intervention from all volunteers to verify compliance and
      help maintain deception/blinding. The results of the study are expected to further our
      understanding of a widely used medical intervention, i.e., placebo, and help assess the
      appropriateness of randomized clinical trials in determining the size of drug effect.
    

Intervention name(s): Hydroxizine; Placebo; hydroxyzine/placebo
Intervention type(s): Drug; Other; Drug
Intervention description(s): 25 mg orally, one time on two different days, 72 hours apart; Matching placebo once on two different days, 72 hours apart.; 25 mg hydroxyzine or placebo once on two different days, 72 hours apart
Intervention MeSH terms: Hydroxyzine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Placebo effect; placebo drug interaction; placebo -controlled clinical trials