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

NCT01501591 | Completed

• 1 other identifier: RAC 2111001
• Study Type: interventional
• Target: 480
• Locations: 1 country
• Sites: 1

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.

Conditions

Placebo Effect; Placebo Drug Interaction

Keywords

Placebo effect; placebo drug interaction; placebo -controlled clinical trials

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (2)

• Mean percent of time of reporting drowsiness on a dichotomous scale.

  seven hours

• Mean percent of time of reporting dryness of mouth

  seven hours

Study Arms (3)

Hydroxyzine

OTHER

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

Placebo

OTHER

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

Hydroxyzine/placebo

OTHER

This group will receive hydroxyzine and placebo in a randomized double-blind placebo-controled crossover design.

Drug: hydroxyzine/placebo

Interventions

Hydroxizine DRUG

25 mg orally, one time on two different days, 72 hours apart

Hydroxyzine

Placebo OTHER

Matching placebo once on two different days, 72 hours apart.

Placebo

hydroxyzine/placebo DRUG

25 mg hydroxyzine or placebo once on two different days, 72 hours apart

Hydroxyzine/placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

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

Sponsors & Collaborators

• King Faisal Specialist Hospital & Research Center: lead

Study Sites (1)

King Faisal Specialist Hospital & research Center

Riyadh, 11211, Saudi Arabia

Location

Related Publications (1)

• 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.

  PMID: 27899067 DERIVED

MeSH Terms

Interventions

Hydroxyzine

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 25, 2011
• First Posted: December 29, 2011
• Study Start: November 1, 2012
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2015
• Last Updated: March 3, 2017

Record last verified: 2016-02

Locations

SA (1)