Clinical trials crossover

Crossover design A clinical trial design in which patients receive, in sequence, the treatment (or the control), and then after a specified time, receive the opposite arm of the trial. This allows patients to serve as their own controls. Randomization should be... 

A preliminary assessment of the effect of food on pharmacokinetics can generally be studied in a single-dose, two-arm, randomised, crossover design. Preliminary information can often be obtained by including a fed occasion in the first, dose-escalating study. This will be insuffi-cent for registration purposes, which require an adequately powered study performed with the final formulation, but the information should be sufficient to indicate whether there is need for restrictions on dosing relative to meals in repeat-dose studies in healthy volunteers and patient clinical trials. 

This latter disadvantage led the crossover design to be described as not the design of choice in clinical trials, where unequivocal evidence of treatment effects is required. Over the last 25 years, many statisticians have been more positive about the place of the crossover design in clinical research. ... 

In an early study, Insel et al. [1983b] compared the efficacy of CMI with that of clorgiline, a monoamine oxidase-A inhibitor, in a controlled crossover study of patients with OCD. Although CMl was effective, patients on clorgiline did not improve at all. Vallejo et al. [1992] conducted a controlled clinical trial of the efficacy of CMl and phenelzine in 30 patients with OCD. The authors reported improvement in both groups however, the lack of a placebo control and the small size of the study groups limit the applicability of these findings. Further studies on the therapeutic role of monoamine oxidase inhibitors in OCD, especially in OCD with comorbid panic disorder, are warranted. 

Wiliam, A.R., Pater, J.L. Carryover and the two-period crossover clinical trial. Biometrics 42(3), 593-599, 1986. 

A number of clinical trials have found clonidine to be superior to placebo in treating ADHD ( 101, 102,103 and 104). However, these studies were generally not as methodologically rigorous as those with either psychostimulants or antidepressants. Clonidine has been used as monodrug therapy and in combination with methylphenidate. Hunt (101) did a crossover study of clonidine alone, methylphenidate alone, and the combination in 25 children with ADHD and conduct disorder. 

Smith S, Rinehart JS, Ruddock VE, et al. Treatment of premenstrual syndrome with alprazolam results of a double-blind, placebo-controlled, randomized crossover clinical trial. Obstet Gynecol 1987 70 37-43. 

A placebo-controlled, randomized clinical trial with monitoring of hypericin and pseudohypericin plasma concentrations was performed to evaluate the increase in dermal photosensitivity in humans after application of high doses of SJW extract (Table 2) (73). The study was divided into a single-dose and a multiple-dose part. In the single dose crossover study, each of the 13 volunteers received either placebo or 900, 1800, or 3600 mg of the SJW extract LI 160. Maximum total hypericin plasma concentrations were observed about four hours after dosage and were 0, 28, 61, and 159ng/mL, respectively. Pharmacokinetic parameters had a dose relationship that appeared to follow linear kinetics (73). 

Zamora-Ros et al [2006] carried out the first work that assessed the bioavailability of resveratrol (provided by different wines) in a regular intervention during 28 day. The analyses were performed by LC-MS/MS. In the first study, 10 healthy males were recruited to consume 300 mL/day of sparkling wine (1.19 mg resveratrol/1). After 28 day of supplementation, urinary trans-and m-resveratrol-3-O-glucuronides were 75 and 38 nmol/g creatinine, respectively. In the second study, 10 healthy females were selected to consume 200 mL of white wine (1.99 mg resveratrol/L) or 200 mL of red wine (12.8 mg resveratrol/L) in a crossover clinical trial. Likewise after 28 days only resveratrol metabolites were detected in morning urine, trans- (205 and 473 nmol/g creatinine) and ra-resveratrol-3-O-glucuronidcs (58 and 140 nmol/g creatinine) were found after white and red wine intake, respectively. Those studies showed that urinary excretion was dose dependent. Furthermore, slight amounts of resveratrol metabolites were also detected at baseline periods. No free resveratrol or piceid were detected in any of the studies. 

PIncus T, Koch GG, Sokka T, et al. A randomized, double-blind crossover clinical trial of diclofenac versus misoprostol versus acetaminophen in patients with osteoarthritis ofthe knees or hip. Arthritis Rheum 2001 44 1587-98. 

Hills M, Armitage P. The two-period crossover clinical trial. Br J Clin Pharmacol 1979 8 7-20. 

A very well controlled and executed recent clinical trial is described as an example [170]. Levonantradol (1 mg every 4h) was administered by i.m. injection and was compared with A -THC (15 mg every 4h) administered orally in a double-blind, crossover study. The patients received severely emeto-... 

With the anthelmintic tetramisole (124) some mood elevating activity in depressed schizophrenics was observed during a double-blind crossover study [306,307]. The (+)-enantiomer of (124), dexamisole, showed effects in depression in small preliminary clinical trials [308].The(—)-antipode,levamisole,was the active anthelmintic in the racemate [309-311], but of its central activity nothing is mentioned. The [Pg.295]

The TQT study is a randomized, placebo- and positive-controlled clinical trial that can adopt a crossover design or a parallel-group design. The traditional four treatment arms are as follows ... 

We noted previously that both crossover and parallel-gronp designs can be employed in TQT studies. As in any other clinical trial, the issue of statistical power is of interest. When commenting on the topic, Mayo (2009) observed as follows The... 

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