Alberto J Espay1, Matthew M Norris2, James C Eliassen2, Alok Dwivedi2, Matthew S Smith2, Christi Banks2, Jane B Allendorfer2, Anthony E Lang2, David E Fleck2, Michael J Linke2, Jerzy P Szaflarski2. 1. From the UC Neuroscience Institute, Department of Neurology (A.J.E., C.B., J.P.S.), and Department of Internal Medicine (M.J.L.), University of Cincinnati; Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E.), Cincinnati; University of Cincinnati Center for Imaging Research (M.M.N., J.C.E., M.S.S., D.E.F.), OH; Division of Biostatistics and Epidemiology (A.D.), Texas Tech University Health Sciences Center, El Paso; The Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson's Disease (A.E.L.), University Health Network and the University of Toronto, Canada; University of Alabama at Birmingham (J.B.A., J.P.S.); and Department of Veterans Affairs Medical Center (M.J.L.), Research Service, Cincinnati, OH. alberto.espay@uc.edu. 2. From the UC Neuroscience Institute, Department of Neurology (A.J.E., C.B., J.P.S.), and Department of Internal Medicine (M.J.L.), University of Cincinnati; Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E.), Cincinnati; University of Cincinnati Center for Imaging Research (M.M.N., J.C.E., M.S.S., D.E.F.), OH; Division of Biostatistics and Epidemiology (A.D.), Texas Tech University Health Sciences Center, El Paso; The Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson's Disease (A.E.L.), University Health Network and the University of Toronto, Canada; University of Alabama at Birmingham (J.B.A., J.P.S.); and Department of Veterans Affairs Medical Center (M.J.L.), Research Service, Cincinnati, OH.
Abstract
OBJECTIVE: To examine the effect of cost, a traditionally "inactive" trait of intervention, as contributor to the response to therapeutic interventions. METHODS: We conducted a prospective double-blind study in 12 patients with moderate to severe Parkinson disease and motor fluctuations (mean age 62.4 ± 7.9 years; mean disease duration 11 ± 6 years) who were randomized to a "cheap" or "expensive" subcutaneous "novel injectable dopamine agonist" placebo (normal saline). Patients were crossed over to the alternate arm approximately 4 hours later. Blinded motor assessments in the "practically defined off" state, before and after each intervention, included the Unified Parkinson's Disease Rating Scale motor subscale, the Purdue Pegboard Test, and a tapping task. Measurements of brain activity were performed using a feedback-based visual-motor associative learning functional MRI task. Order effect was examined using stratified analysis. RESULTS: Although both placebos improved motor function, benefit was greater when patients were randomized first to expensive placebo, with a magnitude halfway between that of cheap placebo and levodopa. Brain activation was greater upon first-given cheap but not upon first-given expensive placebo or by levodopa. Regardless of order of administration, only cheap placebo increased activation in the left lateral sensorimotor cortex and other regions. CONCLUSION: Expensive placebo significantly improved motor function and decreased brain activation in a direction and magnitude comparable to, albeit less than, levodopa. Perceptions of cost are capable of altering the placebo response in clinical studies. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that perception of cost is capable of influencing motor function and brain activation in Parkinson disease.
RCT Entities:
OBJECTIVE: To examine the effect of cost, a traditionally "inactive" trait of intervention, as contributor to the response to therapeutic interventions. METHODS: We conducted a prospective double-blind study in 12 patients with moderate to severe Parkinson disease and motor fluctuations (mean age 62.4 ± 7.9 years; mean disease duration 11 ± 6 years) who were randomized to a "cheap" or "expensive" subcutaneous "novel injectable dopamine agonist" placebo (normal saline). Patients were crossed over to the alternate arm approximately 4 hours later. Blinded motor assessments in the "practically defined off" state, before and after each intervention, included the Unified Parkinson's Disease Rating Scale motor subscale, the Purdue Pegboard Test, and a tapping task. Measurements of brain activity were performed using a feedback-based visual-motor associative learning functional MRI task. Order effect was examined using stratified analysis. RESULTS: Although both placebos improved motor function, benefit was greater when patients were randomized first to expensive placebo, with a magnitude halfway between that of cheap placebo and levodopa. Brain activation was greater upon first-given cheap but not upon first-given expensive placebo or by levodopa. Regardless of order of administration, only cheap placebo increased activation in the left lateral sensorimotor cortex and other regions. CONCLUSION: Expensive placebo significantly improved motor function and decreased brain activation in a direction and magnitude comparable to, albeit less than, levodopa. Perceptions of cost are capable of altering the placebo response in clinical studies. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that perception of cost is capable of influencing motor function and brain activation in Parkinson disease.
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