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

NCT ID: NCT01501591

Last Updated: 2017-03-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 480 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-11-30
• Study Completion Date: 2015-10-31

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.

Conditions

Placebo Effect; Placebo Drug Interaction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: OTHER

Hydroxizine

Intervention Type: DRUG

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.

Group Type: OTHER

Placebo

Intervention Type: OTHER

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.

Group Type: OTHER

hydroxyzine/placebo

Intervention Type: DRUG

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

Interventions

Hydroxizine

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

Intervention Type: DRUG

Placebo

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

Intervention Type: OTHER

hydroxyzine/placebo

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

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

King Faisal Specialist Hospital & Research Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

King Faisal Specialist Hospital & research Center

Riyadh, , Saudi Arabia

Countries

Saudi Arabia

References

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.

Reference Type: DERIVED

PMID: 27899067 (View on PubMed)

Other Identifiers

RAC 2111001

Identifier Type: -

Identifier Source: org_study_id