Measuring Placebo Effect by Elimination and Investigating Mechanism of Action

Measuring Placebo Effect by Elimination and Investigating Its Mechanism of Action

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.

Study Overview

• Status: Completed
• Conditions: Placebo Effect; Placebo Mechanisms of Action
• Intervention / Treatment: Drug: caffeine/placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 180
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Saudi Arabia
  • Riyadh, Saudi Arabia, 11211
    • Center for Clinical Studies & Empirical Ethics, KFSH & RC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; overt then covert caffeine	Drug: caffeine/placebo; caffeine or placebo, either overt or covert
Active Comparator: 2; covert then overt caffeine	Drug: caffeine/placebo; caffeine or placebo, either overt or covert
Active Comparator: 3; overt then covert placebo	Drug: caffeine/placebo; caffeine or placebo, either overt or covert
Active Comparator: 4; covert then overt placebo	Drug: caffeine/placebo; caffeine or placebo, either overt or covert

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: King Faisal Specialist Hospital & Research Center
• Collaborators: King AbdulAziz City for Science and Technology
• Investigators: Principal Investigator: Muhammad M Hammami, MD, PhD, KFSH & RC, Riyadh

Publications and helpful links

General Publications

• Hammami MM, Al-Gaai EA, Alvi S, Hammami MB. Interaction between drug and placebo effects: a cross-over balanced placebo design trial. Trials. 2010 Nov 19;11:110. doi: 10.1186/1745-6215-11-110.

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): February 1, 2009
• Study Completion (Actual): February 1, 2009

Study Registration Dates

• First Submitted: January 23, 2007
• First Submitted That Met QC Criteria: January 23, 2007
• First Posted (Estimate): January 24, 2007

Study Record Updates

• Last Update Posted (Estimate): December 13, 2011
• Last Update Submitted That Met QC Criteria: December 11, 2011
• Last Verified: December 1, 2011

More Information

Terms related to this study

• Keywords: VAS; Caffeine; Placebo effect; Systolic BP
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Purinergic Antagonists; Purinergic Agents; Phosphodiesterase Inhibitors; Purinergic P1 Receptor Antagonists; Central Nervous System Stimulants; Caffeine
• Other Study ID Numbers: RAC# 2051072; KACST:ARP-26-45