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Study Title and Description

The influence of placebo awareness on stimulant drug response in a double-blind trial.



Key Questions Addressed
1 For [population], is caffeine intake above [exposure dose], compared to intakes [exposure dose] or less, associated with adverse effects on cardiovascular outcomes?
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Primary Publication Information
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TitleData
Title The influence of placebo awareness on stimulant drug response in a double-blind trial.
Author JM Nash,KA Holroyd,LA Rokicki,S Kvaal,DB Penzien,
Country
Year 2002
Numbers

Secondary Publication Information
There are currently no secondary publications defined for this study.


Extraction Form: Cardiovascular Design
Design Details
Question... Follow Up Answer Follow-up Answer
What outcome is being evaluated in this paper? Cardiovascular
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What is the objective of the study (as reported by the authors)? In this study, we sought to determine whether drug responses are affected by drug administration instructions informing individuals that they may receive a placebo.
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Provide a general description of the methods as reported by the authors. Information should be extracted based on relevance to the SR (i.e., caffeine related methods) Subjects were 52 (22 male, 30 female) introductory psychology students. Subjects were low-dose caffeine consumers as defined as averaging no more than four caffeine consumption days per week or ingesting no more than 85 mg caffeine on a daily basis. Individuals were excluded if they reported or were found to have consumed caffeine within 24 h of the experiment, were allergic to milk products, had any chronic disease or regularly took any medication for the treatment of a physical or mental disorder, or had blood pressure baseline readings above 140 mmHg systolic or 80 mmHg diastolic. We did not assess for smoking status, alcohol use, or past history of physical or mental disorder. Two of the 52 subjects who participated in the experiment were not included in the statistical analysis. One dropped out because of side effects (at 125 mg caffeine); the other was excluded because a friend had already participated in the study. Thus, 50 subjects were included in the analysis. Each of the 50 subjects was randomly assigned to one of the two drug administration instruction protocols: placebo-uninformed or placebo-informed. Within each of these protocols, subjects were assigned to one of six possible dose orders (PL→125 mg→325 mg; PL→325 mg→125 mg; 125 mg→PL→325 mg; 125 mg→325 mg→PL; 325 mg→PL→125 mg; 325 mg→125 mg→PL) with the constraint of having an equal number of subjects and males in each order. The consent form did not specify caffeine but described it as a mild stimulant that is a safe and widely used preparation with temporary effects that will not last for more than a few hours. The only adverse effect mentioned was the possibility of feeling somewhat jittery for a brief period. Caffeine Capsules The drug, caffeine anhydrous (USP), was prepared in identical gelatin capsules from combinations of caffeine and powdered mild lactose. Dosage levels were 0 mg (placebo), 125 mg caffeine, and 325 mg caffeine. Design and Experimental Manipulation The experiment was conducted in individual sessions in a one between-subjects, two within-subjects (2x3x4; drug administration instructions x dose level x trials) design, with the restriction of having groups largely equivalent in terms of number of subjects and sex distribution. Administration instructions, the between-groups factor, were either placebo-informed or placebo-uninformed drug administration instructions. Dose levels, a within-subjects factor, were 0 mg lactose placebo, 125 mg caffeine (low), and 325 mg caffeine (moderate). Trials, a within-subjects factor, were baseline assessment (T0), drug assessment 1 (T1; 20 min after drug intake), drug assessment 2 (T2; 40 min after drug intake), and drug assessment 3 (T3; 60 min after drug intake). Study Procedure Subjects were instructed to not consume any food or liquid, except water, from 2 h prior to their appointment on the test days. Consistent with caffeine studies, subjects were also instructed to not consume any coffee, tea, chocolate, or soft drinks from 6 h prior to their appointments; however, we did not provide specific instructions regarding nicotine or alcohol use between test days. On all participation days, all task instructions were delivered via audiotape and all measures were administered remotely from an adjoining room. Each subject was given the capsule containing the appropriate dose level (0 mg, 125 mg, 325 mg) for that day. The experimenter was blind to the dose level and drug administration condition. On all three drug administration days (days 1, 2, and 3) there were three assessment trials (T1, T2, T3) to test the effects of the drug. Assessment trials began 20 min, 40 min, and 60 min after drug intake. During each assessment trial, subjects started with simultaneous physiological recordings (systolic blood pressure, diastolic blood pressure, and heart rate). Day 4 was an abbreviated session reserved for baseline recordings of physiological measures. Subjects were allowed 4 min of listening to music to become acclimated. Blood pressure and simultaneous heart rate recordings were then taken. Subjects then rested for another 4 min, followed by a final recording of blood pressure and heart rate. Measures The three physiological responses, heart rate, systolic blood pressure, and diastolic blood pressure, were assessed simultaneously using an automated blood pressure and pulse rate monitor (Model SD-700 A; Industrial & Biomedical Sensors Corporation, Waltham, Mass.). For each of the physiological responses, three measurements were taken over a 4-min period with a 15-s interval between measurements. At each assessment, the median of the three measures was used as the value. Statistical Analysis To assess whether placebo awareness influenced stimulant drug response, two sets of analyses were conducted. The first set of analyses examined drug responses separately under each set of instructions. That is, the analyses assessed whether caffeine produced larger responses than placebo (a) when individuals were informed that they may be taking a placebo (i.e., placebo-informed instructions) and (b) when individuals were not informed that they may receive a placebo (i.e., placebo-uninformed instructions). A series of four planned comparisons were conducted under each set of drug administration instructions. In each comparison, changes from T0 to T3 at the 125-mg and 325-mg caffeine dose levels were compared to changes from T0 to T3 with placebo. A second set of analyses testing the second set of hypotheses was conducted to follow-up on the findings of the first analysis where drug administration instructions had a significant influence as assessed in the above-mentioned analyses. In these analyses, the intention was to determine whether the instructions influence occurred with the placebo doses or with one or both of the active stimulant doses. At each dose level, changes from T0 to T3 under placebo-uninformed instructions were compared to changes from T0 to T3 under placebo-informed instructions. To examine whether differences in the magnitude of drug response could be accounted for by perceived drug strength, the second set of analyses was conducted with perceived drug strength serving as a covariate. In all analyses, F values were adjusted using the Huynd-Felt procedure in cases of violations of assumptions of sphericity. As further protection against making a type I error, the alpha level was adjusted for the number of contrasts tested using Dunn’s multiple comparison procedure (also referred to as Bonferroni t procedure). This procedure has been noted to be highly conservative (Holland and Copenhaver 1988). Even with Bonferroni t corrections, all but a few of the significant hypotheses were significant beyond the P<0.001 alpha level.
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How many outcome-specific endpoints are evaluated? 2
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What is the (or one of the) endpoint(s) evaluated? (Each endpoint listed separately) Blood pressure (SBP, DBP)
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List additional health endpoints (separately). 2 Heart rate
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List additional health endpoints (separately).3
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List additional health endpoints (separately).4
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List additional health endpoints (separately).5
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List additional health endpoints (separately).6
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Clinical, physiological, other Physiological
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What is the study design? Controlled Trial
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Randomized or Non-Randomized? RCT
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What were the diagnostics or methods used to measure the outcome? Objective
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Optional: Name of Method or short description Heart rate, systolic blood pressure, and diastolic blood pressure, were assessed simultaneously using an automated blood pressure and pulse rate monitor (Model SD-700 A; Industrial & Biomedical Sensors Corporation, Waltham, Mass.).
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Caffeine (general) Caffeine (general)
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Coffee, Chocolate, energy drink, gum, medicine/supplement, soda, tea, other?
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Measured or self reported? Measured
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Children, adolescents, adults, or pregnant included? Adults
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What was the reference, comparison, or control group(s)? (e.g. high vs low consumption, number of cups, etc.) Each subject served as their own control (placebo)
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What were the listed confounders or modifying factors as stated by the authors? (e.g. multi-variable components of models.  Copy from methods) Drug strength was included as a covariate in some analyses
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What conflicts of interest were reported? No information provided
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Refid 12021824
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What were the sources of funding? No information provided
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