Vitamin D Oral Replacement in Children With Obesity Related Asthma: VDORA1 Randomized Clinical Trial.

Children with asthma and obesity are more likely to have lower vitamin D levels, but the optimal replacement dose is unknown in this population. The objective of this study is identifying a vitamin D dose in children with obesity-related asthma that safely achieves serum vitamin D levels of ≥ 40 ng/mL. This prospective multisite randomized controlled trial recruited children/adolescents with asthma and body mass index ≥ 85% for age/sex. Part 1 (dose finding), evaluated 4 oral vitamin D regimens for 16 weeks to identify a replacement dose that achieved serum vitamin D levels ≥ 40 ng/mL. Part 2 compared the replacement dose calculated from part 1 (50,000 IU loading dose with 8,000 IU daily) to standard of care (SOC) for 16 weeks to identify the proportion of children achieving target serum 25(OH)D level. Part 1 included 48 randomized participants. Part 2 included 64 participants. In Part 1, no SOC participants achieved target serum level, but 50-72.7% of participants in cohorts A-C achieved the target serum level. In part 2, 78.6% of replacement dose participants achieved target serum level compared with none in the SOC arm. No related serious adverse events were reported. This trial confirmed a 50,000 IU loading dose plus 8,000 IU daily oral vitamin D as safe and effective in increasing serum 25(OH)D levels in children/adolescents with overweight/obesity to levels ≥ 40 ng/mL. Given the critical role of vitamin D in many conditions complicating childhood obesity, these data close a critical gap in our understanding of vitamin D dosing in children.

Protocol for the Vitamin D Oral Replacement in Asthma (VDORA) study.

Obesity and asthma are epidemic in the United States and obesity is an independent risk factor for asthma. Low vitamin D levels (i.e. serum 25-hydroxyvitamin D) have been reported in patients with reduced lung function, more frequent respiratory infections, and asthma exacerbations. Experts have proposed that serum levels > 40 ng/mL are required to offer the immunomodulatory benefits of vitamin D. Low vitamin D levels are common in both obesity and asthma, but it is not known whether supplementation with vitamin D improves asthma symptoms. Guidance for drug development stresses the importance of early phase studies to establish accurate population pharmacokinetics (PK) and drug dosing prior to larger phase 3 trials. The PK of this fat-soluble vitamin in children with increased adiposity are unknown; as are the doses need to reach proposed immunomodulatory levels. The objective of this study is to characterize the PK of vitamin D in children with obesity. Children ages 6--18 years who had physician diagnosed asthma and a body mass index (BMI) >85th percentile will be randomized to receive either standard daily dosing or loading doses followed by standard daily dosing. Blood samples will be obtained to characterize the PK of vitamin D. The results of this study will be used to identify a sufficient dose of vitamin D supplement to raise serum levels above a pre-specified value that may result in anti-inflammatory actions that could improve asthma symptoms.

Teleultrasound for pre-natal diagnosis: A validation study.

INTRODUCTION/PURPOSE: There are no large validation trials comparing teleultrasound to on-site ultrasound. We aim to compare the sensitivity and accuracy of teleultrasound and demonstrate that teleultrasound is not inferior to on-site ultrasound in the pre-natal diagnosis of fetal anomalies. METHODS: All targeted ultrasounds performed between November 2010 and December 2012 were considered. We excluded studies performed at less than 17 weeks' gestation, on multiple gestations and for reasons other than an anatomical survey. Post-natal diagnoses were obtained from a state level mandatory birth defects surveillance programme. Descriptive statistics (sensitivity, specificity, positive and negative predictive values and accuracy) were calculated for both groups. A test of non-inferiority was performed, with the non-inferiority difference set at 0.15. RESULTS: The teleultrasound and on-site ultrasound groups consisted of 2368 and 3145 studies, respectively. The sensitivity of teleultrasound and on-site ultrasound was 57.46% and 76.57%, and the accuracy was 95.9% and 90.97%, respectively. The observed sensitivity difference was -0.1911. The accuracy, specificity, positive and negative predictive values of teleultrasound are similar to on-site ultrasound. DISCUSSION: Teleultrasound is inferior to on-site ultrasound in the detection of fetal anomalies; however, it has improved accuracy, as well as higher negative and positive predictive values. A negative teleultrasound is more likely to identify a non-anomalous fetus, and a positive teleultrasound is more likely to correctly identify an anomalous fetus. CONCLUSION: Teleultrasound has an important role in pre-natal diagnosis for those patients unable or unwilling to travel for an on-site ultrasound.

Effects of coleus forskohlii supplementation on body composition and hematological profiles in mildly overweight women.

PURPOSE: This study investigated the effects of Coleus Forskohlii (CF) on body composition, and determined the safety and efficacy of supplementation. METHODS: In a double blind and randomized manner, 23 females supplemented their diet with ForsLeantrade mark (250 mg of 10% CF extract, (n = 7) or a placebo [P] (n = 12) two times per day for 12-wks. Body composition (DEXA), body weight, and psychometric instruments were obtained at 0, 4, 8 & 12 weeks of supplementation. Fasting blood samples and dietary records (4-d) were obtained at 0 and 12-wks. Side effects were recorded on a weekly basis. Data were analyzed by repeated measures ANOVA and are presented as mean changes from baseline for the CF and placebo groups, respectively. RESULTS: No significant differences were observed in caloric or macronutrient intake. CF tended to mitigate gains in body mass (-0.7 +/- 1.8, 1.0 +/- 2.5 kg, p = 0.10) and scanned mass (-0.2 +/- 1.3, 1.7 +/- 2.9 kg, p = 0.08) with no significant differences in fat mass (-0.2 +/- 0.7, 1.1 +/- 2.3 kg, p = 0.16), fat free mass (-0.1 +/- 1.3, 0.6 +/- 1.2 kg, p = 0.21), or body fat (-0.2 +/- 1.0, 0.4 +/- 1.4%, p = 0.40). Subjects in the CF group tended to report less fatigue (p = 0.07), hunger (p = 0.02), and fullness (p = 0.04). No clinically significant interactions were seen in metabolic markers, blood lipids, muscle and liver enzymes, electrolytes, red cells, white cells, hormones (insulin, TSH, T3, and T4), heart rate, blood pressure, or weekly reports of side effects. CONCLUSION: Results suggest that CF does not appear to promote weight loss but may help mitigate weight gain in overweight females with apparently no clinically significant side effects.

Phase I study of intranodal delivery of a plasmid DNA vaccine for patients with Stage IV melanoma.

BACKGROUND: Based on the likelihood of transfecting large numbers of local antigen-presenting cells, a Phase I study in patients with Stage IV melanoma was conducted to determine the practicality, toxicity of, and immune responses to repeated infusions into a groin lymph node of escalating doses of a DNA plasmid encoding tyrosinase epitopes. METHODS: Cohorts of 8 patients each received 200 microg, 400 microg, or 800 microg of DNA intranodally by pump over 96 hours every 14 days for 4 cycles. Blood was collected for immunologic assays and to measure plasmid in serum prior to treatment, 4 weeks later, and 8 weeks later. Scans and X-rays were performed at baseline and after 8 weeks. RESULTS: Treatment was tolerated well, with only five patients demonstrating Grade 1-2 toxicity. Vaccine delivery by 96-hour infusions of plasmid into a groin lymph node resulted in only 1 episode of catheter leakage in 107 cannulations. Detection of plasmid in serum was rare and transient in two patients. Immune responses by peptide-tetramer assay to tyrosinase 207-216 were detected in 11 of 26 patients. No clinical responses were seen. Survival of the heavily pretreated patients on this trial was unexpectedly long, with 16 of 26 patients alive at a median follow-up of 12 months. CONCLUSIONS: Infusion of a DNA plasmid vaccine into a groin lymph node was practical and well tolerated. Immune responses to a novel tyrosinase epitope were noted. Overall survival in this trial of heavily pretreated patients was unexpectedly long, with 16 of 26 patients alive after a follow-up of 12 months, favoring immune responders.