Israel Medical Association Journal

Background: Infants born very prematurely have functionally and structurally immature gastrointestinal tracts.

Objectives: To assess the safety and tolerability of administration of enteral recombinant human (rh) insulin on formula fed preterm infants and to assess whether enteral administration of rh-insulin enhances gastrointestinal tract maturation by reducing the time to reach full enteral feeding.

Methods: A phase 2, multicenter, double-blind, placebo-controlled, randomized study was conducted. Premature infants (26–33 weeks gestation) were randomized 1:1 to receive insulin 400 μU/ml mixed with enteral feeding or placebo added to their formula. The primary efficacy outcome measure was the number of days required to achieve full enteral feeding. Safety outcomes included adverse events and blood glucose levels.

Results: The study consisted of 33 infants randomized for the safety population and 31 for efficacy analysis. The mean time to full enteral feeding was 6.37 days (95% confidence interval [95%CI] 4.59–8.15) in the enteral rh-insulin treatment group (n=16) and 8.00 days (95%CI 6.20–9.80) in the placebo group (n=15), which represents a statistically significant reduction of 1.63 days (95%CI 0.29–2.97; P = 0.023). There was no difference in blood glucose levels between the groups and none of the participants experienced hypoglycemia. Adverse events occurred in 9/17 (53%) infants in the enteral rh-insulin group and 12/16 (75%) in the placebo group.

Conclusions: Our trial demonstrated that administration of enteral rh-insulin as supplement to enteral nutrition significantly reduced time to achieve full enteral feeding in preterm infants with a gestational age of 26–33 weeks.

Objectives: To assess whether a new herbal-based potentially wake-promoting beverage is effective in counteracting somnolence and reduced post-lunch performance.

Methods: Thirty healthy volunteers were studied on three different days at the sleep clinic. On each visit they ate a standard lunch at noontime, followed by a drink of "Wake up®," 50 mg caffeine, or a placebo in a cross-over double-blind regimen. At 30 and 120 minutes post-drinking, they underwent a battery of tests to determine the effects of the beverage. These included: a) a subjective assessment of alertness and performance based on a visual analog scale, and b) objective function tests: the immediate word recall test, the digit symbol substitution test (DSST), and hemodynamic measurements. The results of the three visits were compared using one-way analysis of variance, with P < 0.05 considered statistically significant.

Results: In all performance tests, subjective vigilance and effectiveness assessment, both Wake up® and caffeine were significantly superior to placebo 30 minutes after lunch. However, at 2 hours after lunch, performance had deteriorated in those who drank the caffeine-containing drink, while Wake up® was superior to both caffeine and placebo. Blood pressure and pulse were higher 2 hours after caffeine ingestion, compared to both Wake up® and placebo.

Conclusions: These results suggest that a single dose of Wake up® is effective in counteracting the somnolence and reduced performance during the post-lunch hours. In the current study it had no adverse hemodynamic consequences.

Methods: We assessed 25 patients with insomnia who were enrolled in a hypnotic study but prior to the study were asked to undergo two full nights in lab polysomnography studies: with and without a placebo. Although they were not explicitly told that they were receiving a placebo, the participants knew that the results of these studies would determine whether they met the criteria to participate in the pharmaceutical study.

Results: Although the participants acknowledged that they were given a placebo, almost all measures of their sleep improved. With placebo, sleep latency was shortened from 55.8 ± 43.5 to 39.8 ± 58.5 minutes (P < 0.05); total sleep time was extended from 283 ± 72.5 to 362.9 ± 56.3 minutes, and sleep efficiency improved from 59.57 ± 14.78 to 75.5 ± 11.70% (P < 0.05). Interestingly, placebo had no effect on the relative sleep stage distribution (percentage of total sleep time), except for a trend toward increased percentage of REM[1] sleep.

Conclusions: Our findings how a clear and significant beneficial effect of placebo on insomnia, despite participants' understanding that they were receiving placebo. These results emphasize the importance of the patients' perception and belief in insomnia treatment, and suggest that in some cases placebo may serve as a treatment.