The Placebo Effect May Involve Modulating Drug Bioavailability
Condition: Placebo Effect; Drug Half Life; Pharmacokinetics
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 interaction. Current interpretation of clinical trials (the
      gold standard of evidence-based-medicine) assumes no interaction, and the mechanism(s)
      underlying such interaction have not been fully explored. One possibility is that the placebo
      effect may modulate drug bioavailability. Using caffeine as a model drug, we have recently
      shown that the placebo effect of caffeine ingestion prolongs caffeine half life. Due to the
      novelty of this finding and its important clinical practice and clinical research
      implications, it needs to be confirmed in another set of subjects and extended to additional
      drugs.

      The results of the study are expected to further our understanding of the mechanism of action
      of a widely used medical intervention, i.e., placebo. The results will be important for both
      clinical practice and clinical research.
    

Detailed description: 
      The total effect of a medication is the sum of its drug effect, placebo effect (meaning
      response of placebo), and their interaction. Current interpretation of clinical trials (the
      gold standard of evidence-based-medicine) assumes no interaction, and the mechanism(s)
      underlying such interaction have not been fully explored. One possibility is that the placebo
      effect may modulate drug bioavailability. Using caffeine as a model drug, we have recently
      shown that the placebo effect of caffeine ingestion prolongs caffeine half life. Due to the
      novelty of this finding and its important clinical practice and clinical research
      implications, it needs to be confirmed in another set of subjects and extended to additional
      drugs.

      DESIGN: Balanced cross-over, single-dose, two-period, two-group deign comparing caffeine,
      paracetamol, cephalexin, and ibuprofen described as such (overt) to the same medication
      described as placebo (covert).

      METHODS: 32, 50, 50, and 30 healthy adult volunteers will be enrolled in the caffeine (300
      mg), paracetamol (500 mg), cephalexin (500 mg), and ibuprofen (400 mg) cross-over studies,
      respectively. Volunteers will be partially deceived to the intervention assignment (i.e., in
      the covert arm). Serum levels of each drug will be blindly determined by locally validated
      HPLC assays. Plasma half life (primary outcome) as well as Cmax, Tmax, and AUC (secondary
      outcomes) of each drug will be determined and analyzed by ANOVA.
    

Intervention name(s): Caffeine, paracetamol, cephalexin, or ibuprofen; Placebo (caffeine, paracetamol, cephalexin, or ibuprofen)
Intervention type(s): Drug; Drug
Intervention description(s): The study has 4 sub-parts (one for each of 4 drugs), each sub-part has a crossover design. In this arm, the volunteer will be given one oral dose of 300 mg caffeine, 500 mg paracetamol, 500 mg cephalexin, or 400 mg ibuprofen and will be told that they are receiving the active drug.; The study has 4 sub-parts (one for each of 4 drugs), each sub-part has a crossover design. In this arm, the volunteer will be given one oral dose of 300 mg caffeine, 500 mg paracetamol, 500 mg cephalexin, or 400 mg ibuprofen and will be told that they are receiving a placebo.
Intervention MeSH terms: Acetaminophen; Cephalexin; Ibuprofen; Caffeine
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Keywords: Placebo effect; drug half life; pharmacokinetics