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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2013 by King Faisal Specialist Hospital & Research Center
Sponsor:
Information provided by (Responsible Party):
King Faisal Specialist Hospital & Research Center
ClinicalTrials.gov Identifier:
NCT01501591
First received: December 25, 2011
Last updated: April 8, 2013
Last verified: April 2013
  Purpose

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 Intervention
Placebo Effect
Placebo Drug Interaction
Drug: Hydroxizine
Other: Placebo
Drug: hydroxyzine/placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by King Faisal Specialist Hospital & Research Center:

Primary Outcome Measures:
  • Area-under-the-curve for drowsiness [ Time Frame: seven hours ] [ Designated as safety issue: No ]
    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 [ Time Frame: seven hours ] [ Designated as safety issue: No ]
    Seven-hour-area-under-the-curve of dryness of the mouth on 100 mm visual analog scales will be determined


Secondary Outcome Measures:
  • Mean percent of time of reporting drowsiness on a dichotomous scale. [ Time Frame: seven hours ] [ Designated as safety issue: No ]
    Mean percent of time of reporting drowsiness on a dichotomous scale will also be determined.

  • Mean percent of time of reporting dryness of mouth [ Time Frame: seven hours ] [ Designated as safety issue: No ]
    Mean percent of time of reporting dryness of mouth on a dichotomous scale will also be determined.


Estimated Enrollment: 480
Study Start Date: December 2011
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01501591

Locations
Saudi Arabia
King Faisal Specialist Hospital & research Center Recruiting
Riyadh, Saudi Arabia, 11211
Contact: Muhammad M Hammami, MD, PhD    96614424527    muhammad@kfshrc.edu.sa   
Principal Investigator: Muhammad M Hammami, MD, PhD         
Sponsors and Collaborators
King Faisal Specialist Hospital & Research Center
  More Information

No publications provided

Responsible Party: King Faisal Specialist Hospital & Research Center
ClinicalTrials.gov Identifier: NCT01501591     History of Changes
Other Study ID Numbers: RAC 2111001
Study First Received: December 25, 2011
Last Updated: April 8, 2013
Health Authority: Saudi Arabia:Saudi National Medical and BioEthics Committee

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 Agents
Histamine Antagonists
Histamine H1 Antagonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014