Clinical trial NCT01501747: The Placebo Effect May Involve Modulating Drug Bioavailability
Official title: The Placebo Effect May Involve Modulating Drug Bioavailability
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Placebo Effect
Drug Half Life
Pharmacokinetics
Keywords: Placebo effect
drug half life
pharmacokinetics
Lead sponsor: King Faisal Specialist Hospital & Research Center
Sponsor class: OTHER
First posted: 2011-12-29
Enrollment: 162
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER

Brief summary: The total effect of a medication is the sum of its drug effect, placebo effect (meaning response of placebo), and their interaction. Current interpretation of clinical trials (the gold standard of evidence-based-medicine) assumes no interaction, and the mechanism(s) underlying such interaction have not been fully explored. One possibility is that the placebo effect may modulate drug bioavailability. Using caffeine as a model drug, we have recently shown that the placebo effect of caffeine ingestion prolongs caffeine half life. Due to the novelty of this finding and its important clinical practice and clinical research implications, it needs to be confirmed in another set of subjects and extended to additional drugs.

The results of the study are expected to further our understanding of the mechanism of action of a widely used medical intervention, i.e., placebo. The results will be important for both clinical practice and clinical research.

Detailed description: The total effect of a medication is the sum of its drug effect, placebo effect (meaning response of placebo), and their interaction. Current interpretation of clinical trials (the gold standard of evidence-based-medicine) assumes no interaction, and the mechanism(s) underlying such interaction have not been fully explored. One possibility is that the placebo effect may modulate drug bioavailability. Using caffeine as a model drug, we have recently shown that the placebo effect of caffeine ingestion prolongs caffeine half life. Due to the novelty of this finding and its important clinical practice and clinical research implications, it needs to be confirmed in another set of subjects and extended to additional drugs.

DESIGN: Balanced cross-over, single-dose, two-period, two-group deign comparing caffeine, paracetamol, cephalexin, and ibuprofen described as such (overt) to the same medication described as placebo (covert).

METHODS: 32, 50, 50, and 30 healthy adult volunteers will be enrolled in the caffeine (300 mg), paracetamol (500 mg), cephalexin (500 mg), and ibuprofen (400 mg) cross-over studies, respectively. Volunteers will be partially deceived to the intervention assignment (i.e., in the covert arm). Serum levels of each drug will be blindly determined by locally validated HPLC assays. Plasma half life (primary outcome) as well as Cmax, Tmax, and AUC (secondary outcomes) of each drug will be determined and analyzed by ANOVA.

Eligibility criteria: Inclusion Criteria:

* Having no evidence of clinically important deviation from normal health as indicated by medical history, vital signs, and clinical laboratory tests.
* Acceptance to abstain from taking any medication other than birth control pills (including over-the-counter drugs) for at least 1 week prior to, and during the study; and from smoking and taking alcohol or caffeine or related xanthenes-containing beverages or food for 48 hours before and throughout each study period.
* Having good peripheral venous access.
* For the caffeine study, habitual daily caffeine intake should be 100-300 mg.

Exclusion Criteria:

* Women should be non-pregnant and non-lactating. For menstruating women, the study will be conducted 5 to 19 days after the last menstrual period and a urine pregnancy test will be performed.
* Should not have history of hypersensitivity to the drug to be tested or to its related compounds.
* Body Mass Index (BMI) should be less than 35 kg/m2.

Primary outcomes:
measure: Plasma half life
timeFrame: 24 hours
Secondary outcomes:
measure: Area under the curve
timeFrame: 24 hours
measure: Tmax
timeFrame: 24 hours
measure: Cmax
timeFrame: 24 hours
Other outcomes:
Locations:
city: Riyadh
country: Saudi Arabia
facility: King Faisal Specialist Hospital & Research Center
Study officials:
References:
citation: Hammami MM, Yusuf A, Shire FS, Hussein R, Al-Swayeh R. Does the placebo effect modulate drug bioavailability? Randomized cross-over studies of three drugs. J Negat Results Biomed. 2017 May 23;16(1):10. doi: 10.1186/s12952-017-0075-2.