title: Understanding the placebo effect in clinical trials for postural tachycardia syndrome.
abstract: Postural tachycardia syndrome (POTS) is characterized by excessive increases in heart rate (HR) upon standing. Previous studies have shown that standing HR decreases over time in POTS patients given placebo. We hypothesized that this reduction is due to cardiovascular physiological alteration, as opposed to psychological benefit from perceived therapy. To prospectively test this hypothesis, we examined the effects of an open-label 'no treatment' intervention (NoRx) compared with a patient-blinded placebo on standing HR in POTS patients. Twenty-one POTS patients participated in a randomized cross-over trial with oral placebo versus NoRx administered at 0900 h. Seated blood pressure (BP) and HR were measured at baseline and every hour for 4 h. Similarly, BP and HR were measured while patients stood for 10 min at these time points. Standing HR decreased significantly over time with both NoRx (112±13 and 103±16 b.p.m. at baseline and 4 h, respectively) and placebo (112±14 and 102±16 b.p.m. at baseline and 4 h, respectively; Ptime<0.001), but this effect was not different between interventions (Pdrug=0.771). Postural tachycardia syndrome patients have exaggerated orthostatic tachycardia in the morning that decreases over time with either placebo or NoRx interventions, suggesting this phenomenon is due to cardiovascular physiological variation. These data highlight the need for a placebo arm in haemodynamic clinical trials in POTS and may have important implications for the diagnosis of these patients.
authors.affiliation: Autonomic Dysfunction Center, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University, Nashville, TN, USA.
authors.forename: Victor C
authors.initials: VC
authors.lastname: Nwazue
authors.forename: Amy C
authors.initials: AC
authors.lastname: Arnold
authors.forename: Vidya
authors.initials: V
authors.lastname: Raj
authors.forename: Bonnie K
authors.initials: BK
authors.lastname: Black
authors.forename: Italo
authors.initials: I
authors.lastname: Biaggioni
authors.forename: Sachin Y
authors.initials: SY
authors.lastname: Paranjape
authors.forename: Carlos
authors.initials: C
authors.lastname: Orozco
authors.forename: William D
authors.initials: WD
authors.lastname: Dupont
authors.forename: David
authors.initials: D
authors.lastname: Robertson
authors.forename: Satish R
authors.initials: SR
authors.lastname: Raj
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001794:Blood Pressure / Q000502:physiology; D002320:Cardiovascular Physiological Phenomena; D002940:Circadian Rhythm / Q000502:physiology; D018592:Cross-Over Studies; D005260:Female; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D008297:Male; D015990:Placebo Effect; D010919:Placebos / Q000008:administration & dosage; D054972:Postural Orthostatic Tachycardia Syndrome / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D011187:Posture; D011446:Prospective Studies; D013997:Time Factors
chemical_list: D010919:Placebos
keywords: diurnal variability; placebo; postural tachycardia syndrome