Placebo EffectNCT01501591
Interaction Between Drug and Placebo Effect:Randomized Placebo Controlled Trials May Not be Accurate in Determining Drug Effect Size
A study testing Hydroxizine in people with Placebo Effect and Placebo Drug Interaction, run by King Faisal Specialist Hospital & Research Center at 1 site in Saudi Arabia.
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. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Placebo Effect, Placebo Drug Interaction
- What is being tested?
- Hydroxizine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 480 participants
- Where
- 1 siteSaudi Arabia
- Study dates
- Nov 2012to Oct 2015
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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).
Who cannot join
- clinically relevant deviation from normal health
- pregnancy or lactation
- hypersensitivity to hydroxyzine or related compounds
Trial locations and contacts
1 site in 1 country.
Saudi Arabia1 site
King Faisal Specialist Hospital & research Center
Riyadh, 11211
About this study
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.
Read the 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
- Being tested
- Hydroxizine, Placebo, hydroxyzine/placebo
- Keywords
- Placebo effect, placebo drug interaction, placebo -controlled clinical trials
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HydroxizineDrug
25 mg orally, one time on two different days, 72 hours apart
PlaceboOther
Matching placebo once on two different days, 72 hours apart.
hydroxyzine/placeboDrug
25 mg hydroxyzine or placebo once on two different days, 72 hours apart
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Other: Placebo |
| Hydroxyzine/placebo | Other | This group will receive hydroxyzine and placebo in a randomized double-blind placebo-controled crossover design. Receives: Drug: hydroxyzine/placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area-under-the-curve for drowsiness
Seven-hour-area-under-the-curve of drowsiness on 100 mm visual analog scales will be determined
Measured: 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
Measured: seven hours
Secondary outcomes (2)
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.
Measured: seven hours
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.
Measured: seven hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Dec 2011 (estimated)
- Study startNov 2012
- Primary completionOct 2015
- Study completionOct 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Placebo EffectStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 480 participants (actual)
Sponsor and investigators
- Lead sponsor
- King Faisal Specialist Hospital & Research Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01501591
- Sponsor's protocol ID
- RAC 2111001
- Status last verified
- Feb 2016
- First submitted
- 25 Dec 2011
- Last updated
- 3 Mar 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 27899067
Study at a glance
From the registry record, last updated by the sponsor on 3 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Interaction Between Drug and Placebo Effect:Randomized Placebo Controlled Trials May Not be Accurate in Determining Drug Effect Size
- ClinicalTrials.gov ID
- NCT01501591
- Acronym / sponsor ID
- RAC 2111001
- Conditions
- Placebo Effect, Placebo Drug Interaction
- Keywords
- Placebo effect, placebo drug interaction, placebo -controlled clinical trials
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 480 participants (actual)
- Lead sponsor
- King Faisal Specialist Hospital & Research CenterUniversity, hospital or other
- Study start
- Nov 2012
- Primary completion
- Oct 2015 (actual)
- Study completion
- Oct 2015 (actual)
- First posted
- 29 Dec 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Hydroxyzine | Other | Drug: HydroxizineThis 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. |
| Placebo | Other | Other: PlaceboThis 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. |
| Hydroxyzine/placebo | Other | Drug: hydroxyzine/placeboThis group will receive hydroxyzine and placebo in a randomized double-blind placebo-controled crossover design. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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).
Key exclusion criteria (3 listed)
- clinically relevant deviation from normal health
- pregnancy or lactation
- hypersensitivity to hydroxyzine or related compounds
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hydroxizine25 mg orally, one time on two different days, 72 hours apart | Drug | Hydroxyzine |
| PlaceboMatching placebo once on two different days, 72 hours apart. | Other | Placebo |
| hydroxyzine/placebo25 mg hydroxyzine or placebo once on two different days, 72 hours apart | Drug | Hydroxyzine/placebo |
Primary outcome
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
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
2 secondary outcomes
Mean percent of time of reporting drowsiness on a dichotomous scale.
Time frame: seven hours
Mean percent of time of reporting dryness of mouth
Time frame: seven hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Mar 2017.
- Derived from this study: PubMed 27899067Hammami 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Hydroxizine in people with Placebo Effect and Placebo Drug Interaction, run by King Faisal Specialist Hospital & Research Center at 1 site in Saudi Arabia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Saudi Arabia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area-under-the-curve for drowsiness (time frame: seven hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01501591, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Mar 2017; AzTrials last refreshed its copy on 29 Oct 2026.