Interaction Between Drug and Placebo Effect:Randomized Placebo Controlled Trials May Not be Accurate in Determining Drug Effect Size

Placebo Effect Clinical Trial

Official title:

Interaction Between Drug and Placebo Effect:Randomized Placebo Controlled Trials May Not be Accurate in Determining Drug Effect Size

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01501591
• Other study ID #: RAC 2111001
• Status: Completed
• Phase: N/A
• First received: December 25, 2011
• Last updated: March 1, 2017
• Start date: November 2012
• Est. completion date: October 2015

Study information

• Verified date: February 2016
• Source: King Faisal Specialist Hospital & Research Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 480
• Est. completion date: October 2015
• Est. primary completion date: October 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• Placebo Drug Interaction
• Placebo Effect

Intervention

Drug:
• Hydroxizine
25 mg orally, one time on two different days, 72 hours apart

Other:
• Placebo
Matching placebo once on two different days, 72 hours apart.

Drug:
• hydroxyzine/placebo
25 mg hydroxyzine or placebo once on two different days, 72 hours apart

Locations

Country	Name	City	State
Saudi Arabia	King Faisal Specialist Hospital & research Center	Riyadh

Sponsors (1)

Lead Sponsor	Collaborator
King Faisal Specialist Hospital & Research Center

Country where clinical trial is conducted

Saudi Arabia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area-under-the-curve for drowsiness	Seven-hour-area-under-the-curve of drowsiness on 100 mm visual analog scales will be determined	seven hours
Primary	Area-under-the-curve for dryness of the mouth	Seven-hour-area-under-the-curve of dryness of the mouth on 100 mm visual analog scales will be determined	seven hours
Secondary	Mean percent of time of reporting drowsiness on a dichotomous scale.	Mean percent of time of reporting drowsiness on a dichotomous scale will also be determined.	seven hours
Secondary	Mean percent of time of reporting dryness of mouth	Mean percent of time of reporting dryness of mouth on a dichotomous scale will also be determined.	seven hours