Safety and tolerability of chronic intranasal oxytocin in older men: results from a randomized controlled trial.

RATIONALE: Most studies evaluating the safety and tolerability of intranasal oxytocin (OT) have not reported consistent adverse events (AEs), but they have largely focused on young men and single-dose administration. Thus, it is unclear whether these findings translate to older individuals and with longer administration periods. OBJECTIVE: Extending previous work, this study investigated the safety and tolerability of chronic intranasal OT in generally healthy older men. METHODS: Data were from a randomized, placebo (P)-controlled, double-blind clinical trial evaluating the effects of 4 weeks of self-administered intranasal OT (24 IU twice daily) in older adults with no major physical or cognitive impairments. Heart rate, blood pressure, urine osmolality, and serum metabolic biomarkers were obtained before and at the end of the intervention. AEs were collected during the first 3 weeks and 1 week after cessation of treatment. RESULTS: Of 103 participants recruited, 95 were randomized and received the intervention (OT = 49, P = 46). OT had no significant impact on cardiovascular, urine, or serum measures. The AEs reported for both treatments were generally mild and few in number, though one participant assigned to OT and two assigned to P dropped out due to AEs. Relative to P, OT did not significantly increase the likelihood of reporting AEs, nor the number or severity of AEs reported. CONCLUSION: Chronic intranasal OT appears safe and well-tolerated in generally healthy older men. These findings provide support for continued human research on potential benefits of chronic OT in older adult populations.

Tolerance of simulated amniotic fluid in premature neonates.

OBJECTIVE: To assess the tolerance of simulated amniotic fluid enterally administered in premature neonates. DESIGN: A multicentered, Phase I, dose-escalation trial was accomplished among 30 preterm neonates. Groups of 10 patients received 5, 10, or 20 mL/kg/d enterally of the amniotic fluid solution, divided into every-3-hour dosing, for 3 days. MAIN OUTCOME MEASURES: Amount and character of emesis, stools, and gastric residuals; changes in abdominal girth; presence of a skin rash; blood pressure instability; the diagnosis of necrotizing enterocolitis (NEC) or intestinal perforation. RESULTS: Thirty patients were studied: 10 received 5 mL/kg/d, 10 received 10 mL/kg/d, and 10 received 20 mL/kg/d of amniotic solution. Gestational ages ranged from 25 to 31 weeks. The Data Safety and Monitoring Board met after each group of 10 patients completed the study, reviewed the outcome measurements, and recommended continuance of the study. Dosing was discontinued for 3 patients prior to receiving all 24 doses because of gastric residuals (n = 1; 5 mL/kg), stage I NEC (n = 1; 10 mL/kg), or symptomatic patent ductus arteriosus (n = 1; 20 mL/kg). The remaining patients completed the doses with no evidence of intolerance: specifically, no increased gastric residuals, increased abdominal girth, diarrhea, blood pressure change, rash, NEC, or intestinal perforation. CONCLUSIONS: Enteral administration of an amniotic fluid-like solution to preterm neonates is well tolerated in doses