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The Placebo Effect May Involve Modulating Drug Bioavailability

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
King Faisal Specialist Hospital & Research Center
ClinicalTrials.gov Identifier:
NCT01501747
First received: December 26, 2011
Last updated: April 8, 2013
Last verified: April 2013
  Purpose

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.


Condition Intervention
Placebo Effect
Drug Half Life
Pharmacokinetics
Drug: Caffeine, paracetamol, cephalexin, or ibuprofen
Drug: Placebo (caffeine, paracetamol, cephalexin, or ibuprofen)

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Outcomes Assessor)
Official Title: The Placebo Effect May Involve Modulating Drug Bioavailability

Resource links provided by NLM:


Further study details as provided by King Faisal Specialist Hospital & Research Center:

Primary Outcome Measures:
  • Plasma half life [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    The study has 4 sub-parts (one for eah of 4 drugs), each sub-part has a crossover design. The time frame to measure the outcome depends on the drug studied. For caffeine it is 24 hours, for paracetamol, it is 14 hours, for cephalexin, it is 6 hours, and for ibuprofen, it is 10 hours.


Secondary Outcome Measures:
  • Area under the curve [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    The study has 4 sub-parts (one for eah of 4 drugs), each sub-part has a crossover design. The time frame to measure the outcome depends on the drug studied. For caffeine it is 24 hours, for paracetamol, it is 14 hours, for cephalexin, it is 6 hours, and for ibuprofen, it is 10 hours.

  • Tmax [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    The study has 4 sub-parts (one for eah of 4 drugs), each sub-part has a crossover design. The time frame to measure the outcome depends on the drug studied. For caffeine it is 24 hours, for paracetamol, it is 14 hours, for cephalexin, it is 6 hours, and for ibuprofen, it is 10 hours.

  • Cmax [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    The study has 4 sub-parts (one for eah of 4 drugs), each sub-part has a crossover design. The time frame to measure the outcome depends on the drug studied. For caffeine it is 24 hours, for paracetamol, it is 14 hours, for cephalexin, it is 6 hours, and for ibuprofen, it is 10 hours.


Enrollment: 162
Study Start Date: February 2012
Study Completion Date: February 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: overt drug
The study has 4 sub-parts (one for each of 4 drugs), each sub-part has a crossover design. In this arm, the volunteer will be given one oral dose of 300 mg caffeine, 500 mg paracetamol, 500 mg cephalexin, or 400 mg ibuprofen and will be told that they are receiving such medication.
Drug: Caffeine, paracetamol, cephalexin, or ibuprofen
The study has 4 sub-parts (one for each of 4 drugs), each sub-part has a crossover design. In this arm, the volunteer will be given one oral dose of 300 mg caffeine, 500 mg paracetamol, 500 mg cephalexin, or 400 mg ibuprofen and will be told that they are receiving the active drug.
Placebo Comparator: Placebo (Covert drug)
The study has 4 sub-parts (one for each of 4 drugs), each sub-part has a crossover design. In this arm, the volunteer will be given one oral dose of 300 mg caffeine, 500 mg paracetamol, 500 mg cephalexin, or 400 mg ibuprofen and will be told that they are receiving a placebo.
Drug: Placebo (caffeine, paracetamol, cephalexin, or ibuprofen)
The study has 4 sub-parts (one for each of 4 drugs), each sub-part has a crossover design. In this arm, the volunteer will be given one oral dose of 300 mg caffeine, 500 mg paracetamol, 500 mg cephalexin, or 400 mg ibuprofen and will be told that they are receiving a placebo.

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

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01501747

Locations
Saudi Arabia
King Faisal Specialist Hospital & Research Center
Riyadh, Saudi Arabia, 11211
Sponsors and Collaborators
King Faisal Specialist Hospital & Research Center
  More Information

No publications provided

Responsible Party: King Faisal Specialist Hospital & Research Center
ClinicalTrials.gov Identifier: NCT01501747     History of Changes
Other Study ID Numbers: RAC2101105
Study First Received: December 26, 2011
Last Updated: April 8, 2013
Health Authority: Saudi Arabia: Ethics Committee

Keywords provided by King Faisal Specialist Hospital & Research Center:
Placebo effect
drug half life
pharmacokinetics

Additional relevant MeSH terms:
Acetaminophen
Caffeine
Cephalexin
Ibuprofen
Analgesics
Analgesics, Non-Narcotic
Anti-Bacterial Agents
Anti-Infective Agents
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antipyretics
Antirheumatic Agents
Central Nervous System Agents
Central Nervous System Stimulants
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Phosphodiesterase Inhibitors
Physiological Effects of Drugs
Purinergic Agents
Purinergic Antagonists
Purinergic P1 Receptor Antagonists
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014