Interaction Between Drug and Placebo Effect:Randomized Placebo Controlled Trials May Not be Accurate in Determining Drug Effect Size
- Conditions
- Placebo Drug InteractionPlacebo Effect
- Interventions
- Registration Number
- NCT01501591
- Brief 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 480
- Age of 18 to 50 years;
- Being healthy,
- Able to abstain from smoking and alcohol
- Medication-free for one week
- Able to reproducibly express oneself using a 100 mm visual analog scale (VAS).
- clinically relevant deviation from normal health
- pregnancy or lactation
- hypersensitivity to hydroxyzine or related compounds
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo This group will receive a placebo twice on two days; on one day described by the investigator as hydroxyzine and on the other day described by the investigator as placebo, in a randomized balanced crossover design. Hydroxyzine/placebo hydroxyzine/placebo This group will receive hydroxyzine and placebo in a randomized double-blind placebo-controled crossover design. Hydroxyzine Hydroxizine This group will receive a first generation H-1 receptor antagonist, hydroxyzine (25 mg) twice on two days; on one day described by the investigator as hydroxyzine and on the other day described by the investigator as placebo, in a randomized balanced crossover design.
- Primary Outcome Measures
Name Time Method Area-under-the-curve for drowsiness seven hours Seven-hour-area-under-the-curve of drowsiness on 100 mm visual analog scales will be determined
Area-under-the-curve for dryness of the mouth seven hours Seven-hour-area-under-the-curve of dryness of the mouth on 100 mm visual analog scales will be determined
- Secondary Outcome Measures
Name Time Method Mean percent of time of reporting drowsiness on a dichotomous scale. seven hours Mean percent of time of reporting drowsiness on a dichotomous scale will also be determined.
Mean percent of time of reporting dryness of mouth seven hours Mean percent of time of reporting dryness of mouth on a dichotomous scale will also be determined.
Trial Locations
- Locations (1)
King Faisal Specialist Hospital & research Center
🇸🇦Riyadh, Saudi Arabia