Measuring Placebo Effect by Elimination and Investigating Mechanism of Action

Study Overview
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Brief Summary
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We propose to measure the effect of placebo by elimination as well as by a balanced placebo design, determine its interaction with active drug, and explore whether placebo exerts part of its effect at the pharmacokinetics level.

Detailed Description
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Placebos have been in use for centuries in medical practice. However, there is continued controversy regarding their effectiveness and mechanisms of action. The results of the study are expected to further our understanding of a widely used medical intervention, i.e., placebo, and of how to maximize its potential beneficial effect. It will also help assess the appropriateness of measuring the placebo effect by elimination, which has important ethical implications in relation to the design of randomized clinical trials. Comparison: caffeine vs placebo. Dependent variables:4 hours area under the curve (AUC) of pharmacodynamics endpoints as well as pharmacokinetics endpoints in a subgroup.

Official Title
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Measuring Placebo Effect by Elimination and Investigating Its Mechanism of Action

Conditions
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Placebo Effect, Placebo Mechanisms of Action

Intervention / Treatment
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* Drug: caffeine/placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and nonpregnant females 18 and 40 years of age with at least high school education. Exclusion criteria: Include evidence of clinically relevant deviation from normal health (such that it may affect the endpoints, make the ingestion of caffeine dangerous, or affect the pharmacokinetics/pharmacodynamics of caffeine), Pregnancy, Poor venous access, Hypertension (more than 140/90), Heart disease, History of panic attacks, Average daily caffeine consumption of more than 300 or less than 100 mg, Smoking, Alcohol abuse, Taking any medication other than birth control bills (including over-the-counter drugs) within one week from starting the study, Hypersensitivity to caffeine or related compounds, Hemoglobin of less than 13 gm/L, and recent (one week) acute illness

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>overt then covert caffeine | Drug: caffeine/placebo<br>* caffeine or placebo, either overt or covert<br>|
| Active Comparator: 2<br>covert then overt caffeine | Drug: caffeine/placebo<br>* caffeine or placebo, either overt or covert<br>|
| Active Comparator: 3<br>overt then covert placebo | Drug: caffeine/placebo<br>* caffeine or placebo, either overt or covert<br>|
| Active Comparator: 4<br>covert then overt placebo | Drug: caffeine/placebo<br>* caffeine or placebo, either overt or covert<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 4 hours area under the curve (AUC) of peripheral systolic blood pressure |  | 4 hours | 
| 4 hours area under the curve (AUC) of energy level measured by Visual Analogue Scales. |  | 4 hours | 
| 4 hours area under the curve (AUC) of alertness level measured by Visual Analogue Scales. |  | 4 hours | 
| 4 hours area under the curve (AUC) of nausea measured by Visual Analogue Scales. |  | 4 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax of serum caffeine (in a subgroup) |  | 4 hours | 
| Tmax of serum caffeine (in a subgroup) |  | 4 hours | 
| t1/2 of serum caffeine (in a subgroup) |  | 14 hours | 
| AUC of serum caffeine (in a subgroup) |  | 14 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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VAS, Placebo effect, Caffeine, Systolic BP