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

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ClinicalTrials.gov Identifier: NCT01501591
Recruitment Status : Completed
First Posted : December 29, 2011
Last Update Posted : March 3, 2017
Sponsor:
Information provided by (Responsible Party):

Study Description
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.

Condition or disease Intervention/treatment
Placebo Effect Placebo Drug Interaction Drug: Hydroxizine Other: Placebo Drug: hydroxyzine/placebo

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.


Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 480 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Interaction Between Drug and Placebo Effect:Randomized Placebo Controlled Trials May Not be Accurate in Determining Drug Effect Size
Study Start Date : November 2012
Primary Completion Date : October 2015
Study Completion Date : October 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Drug Reactions
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Hydroxyzine
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.
Drug: Hydroxizine
25 mg orally, one time on two different days, 72 hours apart
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.
Other: Placebo
Matching placebo once on two different days, 72 hours apart.
Hydroxyzine/placebo
This group will receive hydroxyzine and placebo in a randomized double-blind placebo-controled crossover design.
Drug: hydroxyzine/placebo
25 mg hydroxyzine or placebo once on two different days, 72 hours apart


Outcome Measures

Primary Outcome Measures :
  1. Area-under-the-curve for drowsiness [ Time Frame: seven hours ]
    Seven-hour-area-under-the-curve of drowsiness on 100 mm visual analog scales will be determined

  2. Area-under-the-curve for dryness of the mouth [ Time Frame: 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 :
  1. Mean percent of time of reporting drowsiness on a dichotomous scale. [ Time Frame: seven hours ]
    Mean percent of time of reporting drowsiness on a dichotomous scale will also be determined.

  2. Mean percent of time of reporting dryness of mouth [ Time Frame: seven hours ]
    Mean percent of time of reporting dryness of mouth on a dichotomous scale will also be determined.


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01501591


Locations
Saudi Arabia
King Faisal Specialist Hospital & research Center
Riyadh, Saudi Arabia, 11211
Sponsors and Collaborators
King Faisal Specialist Hospital & Research Center
More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: King Faisal Specialist Hospital & Research Center
ClinicalTrials.gov Identifier: NCT01501591     History of Changes
Other Study ID Numbers: RAC 2111001
First Posted: December 29, 2011    Key Record Dates
Last Update Posted: March 3, 2017
Last Verified: February 2016

Keywords provided by King Faisal Specialist Hospital & Research Center:
Placebo effect
placebo drug interaction
placebo -controlled clinical trials

Additional relevant MeSH terms:
Hydroxyzine
Antipruritics
Dermatologic Agents
Histamine H1 Antagonists
Histamine Antagonists
Histamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs