Clinical trial NCT01501591: Interaction Between Drug and Placebo Effect:Randomized Placebo Controlled Trials May Not be Accurate in Determining Drug Effect Size
Official title: Interaction Between Drug and Placebo Effect:Randomized Placebo Controlled Trials May Not be Accurate in Determining Drug Effect Size
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Placebo Effect
Placebo Drug Interaction
Keywords: Placebo effect
placebo drug interaction
placebo -controlled clinical trials
Lead sponsor: King Faisal Specialist Hospital & Research Center
Sponsor class: OTHER
First posted: 2011-12-29
Enrollment: 480
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: Inclusion Criteria:

* 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).

Exclusion Criteria:

* clinically relevant deviation from normal health
* pregnancy or lactation
* hypersensitivity to hydroxyzine or related compounds

Primary outcomes:
measure: Area-under-the-curve for drowsiness
timeFrame: seven hours
measure: Area-under-the-curve for dryness of the mouth
timeFrame: seven hours
Secondary outcomes:
measure: Mean percent of time of reporting drowsiness on a dichotomous scale.
timeFrame: seven hours
measure: Mean percent of time of reporting dryness of mouth
timeFrame: seven hours
Other outcomes:
Locations:
city: Riyadh
country: Saudi Arabia
facility: King Faisal Specialist Hospital & research Center
Study officials:
References:
citation: Hammami MM, Hammami S, Al-Swayeh R, Al-Gaai E, Farah FA, De Padua SJ. Drug*placebo interaction effect may bias clinical trials interpretation: hybrid balanced placebo and randomized placebo-controlled design. BMC Med Res Methodol. 2016 Nov 29;16(1):166. doi: 10.1186/s12874-016-0269-1.