Crossover design, randomization

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... 

Randomized Crossover Design Subjects are divided into placebo and active groups. After some time these two groups crossover the initial placebo group now becoming the active group and vice versa. There may be a washout period before the crossover to enable the effect of the placebo and active to wash out. This method requires a smaller number of subjects and is useful in cases for studying rare or more stable illnesses. 

Miller et 1988 n = 12 adolescents S. n = 6 n = 6 Age 10-17 years Treatments in randomized order with 3-week washout period 1. 250-mg elemental Ca as CaCOs (enriched with Ca) Compare CaAbs for CCM versus CaCOa using dual isotope mettiod using a crossover design and measured urinary isotope ratio after 24 h Mean FxAbs SEM results 1. CCM 36.2 2.7% (range 27.3-53.3%) 2. CaC03 26.4 2J2% (range 12.8-39.6%) Ctest for FxAbs difference CCM > CaCOa (p <. 03)... 

Assessed the effect of oligofructose or inulin -h oligofructose vs placebo on Ca Abs in a balanced, randomized, crossover design using dual isotope... 

Assessed benefits due to enhanced Ca absorption resulting from the addition of modest amounts of long-chain inulin enriched widi oligofructose in a balanced randomized crossover design. Ca Abs measured using dual-isotope methodology via the ratio of Ca with Ca (intravenous tracer) as it appeared in urine collected over 48 hr. 

In another study, the difference in fractional absorption between Ca from CCM and CaCOa was tesfed in 12 healthy adolescents (6 males and 6 females) aged 10-17 years using a 2-period crossover design (Miller et al., 1988). The average ( SEM) dietary Ca intake based on a food frequency quesfionnaire was 600.4 65.7 mg/day. The order of Ca supplementation for groups was randomized and for each treatment two tablets were ingested with a standardized breakfast. Each tablet contained... 

A randomized crossover design has theoretical appeal because it eliminates the largest source of experimental variance interindividual variability. This could significantly enhance statistical power and permit much smaller samples sizes to detect a treatment effect. Unfortunately, a crossover design is appropriate only in rare cases in psychopharmacology, namely in studies ... 

In the crossover design, patients with an episode are given medication and brought into a remission, then maintained on medication for 2 to 3 months. Those who are successfully maintained in remission are then entered into a double-blind phase in which they are randomly assigned to either stay on the medication or switched to a placebo. Both groups are otherwise treated identically and followed up for a specified period of time, usually 1 year. The outcome measure is relapse into a depressive episode. 

A higher percentage of patients would be expected to relapse in the crossover design for two reasons. First, a significant portion of the patients in the crossover study had, in fact, responded specifically to the drug treatment. After a period of stabilization, these patients were randomly reassigned to placebo and thus would be expected to relapse. Second, a basic problem in the crossover design is that withdrawal symptoms can mimic the recurrence of depressive symptoms. That is true for the SSRIs, particularly fluvoxamine and paroxetine, because of their relatively short half-lives. 

Giannini (260) studied 24 patients in a random-assignment crossover design, finding verapamil superior to clonidine however, quantitative measures of change, such as BPRS scores, were not provided. 

Garfinkel et al. (168) conducted an investigation of melatonin s effects on sleep quality in 12 elderly subjects with insomnia [seven men, five women mean age, 76 years (range, 68 to 93 years standard deviation (SD), 8 years)]. These authors used a randomized, double-blind, crossover design with 2 mg controlled-release melatonin or a placebo taken 2 hours before desired bedtime every night for 3 weeks. After a 1-week washout, the subjects then received 3 weeks treatment with the other preparation. Compared with placebo, the controlled-release melatonin improved the sleep quality of these elderly subjects and was well tolerated. Further, 2 months treatment with 2 mg of controlled-release melatonin in these relatively healthy elderly subjects was much more effective than 1 week of treatment ( 168). 

The systemic availability of inhaled budesonide has been measured in 15 healthy volunteers, using an open crossover design. Each subject was given three treatments, intravenous budesonide 0.5 mg, inhaled budesonide (from a metered-dose inhaler with a Nebuhaler) 1 mg (200 micrograms x 5) plus oral charcoal, and inhaled budesonide 1 mg without oral charcoal. The treatment order was randomized. The mean systemic availability of inhaled budesonide compared with intravenous budesonide was 36% with charcoal and 35% without charcoal, indicating that the absorption of budesonide from the gastrointestinal tract did not contribute to its systemic availability. Pulmonary deposition was 36% with charcoal and 34% without. When the inhaler was used incorrectly, that is, the canister was shaken only before the first of the five inhalations, systemic availability fell by 50%. This shows that the performance of each inhaler is very dependent on proper use (16). 

Diltiazem interacts with lovastatin but not with pravastatin (96). In 10 healthy volunteers given lovastatin orally with or without intravenous diltiazem in a randomized, two-way, crossover design, the interaction of diltiazem with lovastatin was primarily a first-pass effect, due to inhibition of CYP3A4 (97). Thus, drug interactions with diltiazem may become evident when a patient is switched from intravenous to oral dosing. 

The clinical pharmacokinetic-pharmacodynamic study had a double blind, randomized, five-way crossover design, with at least seven days elapsing between trials. Twelve healthy volunteers participated and the treatment conditions were ... 

A single-center, open-label, randomized, balanced, singledose, two-treatment (fed versus fasted), two-period crossover design. In one trial period subjects were dosed after fasting (= fasted trial period), and in the other trial period subjects were dosed after consuming a high fat breakfast (= fed trial period). Subjects were randomized to the sequence of trial periods. The washout period between trial periods was at least 5 days which approximated to > 10 Drug XYZ apparent terminal half-lives. 

Design, Treatment and Sample Size Single-center, single-dose, double-blind, randomized, two-way crossover design 20 pediatric type I diabetic subjects (10 per age class) of either gender. The 2 age classes were build by children aged between 5 and 11 years and adolescents aged between 12 and 17. 

Erythromycin 1200 mg/day or placebo for 7 days was given to 14 healthy men in a double-blind, randomized, crossover design (5). On the sixth day they took a single oral dose of brotizolam 0.5 mg and blood samples were taken for 24 hours. Erythromycin significantly increased the Cmax, AUC, and half-life of brotizolam. 

Sedation, cognition, and mood during midazolam infusion in 20 volunteers with red hair and 19 with non-red (blond or brown) hair were studied in a randomized, placebo-controlled, crossover design, to test the... 

The pharmacokinetics and absolute oral systemic availability of zaleplon have been assessed in a partially randomized, single-dose, crossover study in 23 healthy subjects, who received intravenous infusions of zaleplon 1 and 2.5 mg during the first and second periods and were then randomly assigned to receive an oral dose of 5 mg or an intravenous infusion of 5 mg in a crossover design (7). The oral and intravenous doses of zaleplon were well tolerated. Somnolence, abnormal vision, diplopia, and dizziness were the most commonly reported adverse events. 

The initial assessment of the potential of ZT-1 to improve cognition showed that it could antagonize the cognitive impairment induced by scopolamine in healthy elderly volunteers. The study was conducted according to a randomized, placebo and positive-controlled, double-blind and crossover design. Donepezil was a positive internal control. 

Staedt, LL, Lewellng, H., Gladisch, R., Kortsick, C., Hagmiiller, E., Holm, E. Effects of ornithine aspartate on plasma ammonia and plasma amino acids in patients with cirrhosis. A double-blind, randomized study using a four-fold crossover design. J. Hepatol. 1993 19 424-430... 

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