Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA376807 | ENA |
REPOSITORIES: ENA
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Project description:<p>Individuals with Urea Cycle Disorders (UCD) cannot remove ammonia, a waste product, from the blood. At present there is little information on the use of sodium phenylbutyrate (Buphenyl™) in children with argininosuccinic aciduria (ASA). It is hoped that this drug may help lower ammonia and argininosuccinic acid levels in patients with ASA. Through this study we hope to learn whether the use of sodium phenylbutyrate (Buphenyl™) in patients with ASA, in addition to diet and arginine therapy, will decrease liver damage and the number of periods during which ammonia levels are high.</p> <p>The primary study objective is to determine if the treatment of ASA patients with sodium phenylbutyrate (Buphenyl™) in conjunction with lowered doses of arginine improves liver function as measured by short-term assessment of synthetic activity and the use of stable isotope tracers to assess ureagenesis and nitric oxide production.</p> <p>Twelve patients with ASA will be studied using a randomized, cross-over design. Medical records will be reviewed to confirm the diagnosis prior to enrollment. Patients will be on the each arm of the study for one week each preceded by a three day washout period. Patients will come to the Baylor College of Medicine General Clinical Research Center in Texas Children's Hospital for an inpatient hospitalization. This hospitalization is for diet control, clinical evaluation, and stable isotope infusions for measurement of in vivo rates of ureagenesis and nitric oxide production. During the washout periods Buphenyl™ or other alternative route medications, e.g., benzoate, will be discontinued and arginine will be administered at the standard therapeutic dose of 500 mg/kg/day or 10 grams/m2. </p> <p>Following randomization, subjects will be maintained on either high-dose arginine (500 mg/kg/day or 10 grams/m2) alone, or the alternative of low-dose arginine (100 mg/kg/d or 2 grams/m2) along with sodium phenylbutyrate (500 mg/kg/day or 10 grams/m2). For the second week they will be crossed over to the other arm of the study preceded by another three day washout. Previous medications and dietary protein intake (0.6 g/kg/day or current metabolic diet) will be continued during both arms of the study. The two arms may be performed as separate ten-day admissions.</p> <p>The decision to design the study with two arms, high-dose arginine and low-dose arginine/Buphenyl™, was reached after weighing several considerations. First, the current accepted practice for treatment of ASA is high-dose arginine. Based on metabolic flux studies, we have quantified the effects of this dose of arginine as compared to standard doses of Buphenyl™/phenylacetate on ureagenesis. Since the study is not designed or intended to address the independent effects of Buphenyl™ as compared to arginine alone, Buphenyl™ was added for safety reasons to accommodate loss of clearance of nitrogen by decreasing the arginine dose.</p> <p>Moreover, based on our experience with recruiting for previous versions of this study, most ASA patients with liver dysfunction are on an alternative route ammonia scavenger medication in addition to arginine. We found that this has in fact become an accepted practice.</p> <p>Hence, when considering study design from both a safety and recruitment perspective, it was most reasonable to design the study to investigate specifically the hypothesis that the production and presence of argininosuccinic acid leads to liver dysfunction. Since both low-dose arginine with Buphenyl™ and high-dose arginine alone lead to a decreased production of argininosuccinic acid, and both are currently accepted therapies in ASA and UCDs in general, the need to address their effects distinctly is not being investigated at this time.</p> <p>Sodium phenylbutyrate dosage will be 500 mg/kg/day in patients weighing less than 20kg and 10 g/m2/day in larger patients. Daily dosage will be given in equally divided doses 4 times per day. In order to ensure that the study remains double-blind to investigators, study staff and subjects, the Investigational Pharmacy Service at Texas Children's Hospital will dispense both the Buphenyl™ and arginine in powder form which is compounded into capsules or will be mixed with syrpalta (up to 5 grams will dissolve in 10cc liquid) and administered orally or through nasogastric or gastrostomy tube. No nasogastric tube should be placed or gastrostomy performed solely for the purpose of inclusion in this study. Because the reported adverse effects of sodium phenylbutyrate include gastritis, participants will be started on a standard dose of ranitidine (Zantac™), or comparable drug, during both arms of the study. </p>
| phs001305 | dbGaP
Project description:A Randomized, Double-Blind, Crossover Study of Sodium Phenylbutyrate (Buphenyl) and Low-Dose Arginine (100mg/kg/day) Compared to High-Dose Arginine (500 mg/kg/day) Alone in Patients with Argininosuccinic Aciduria (ASA) - UCDC 5102
| PRJNA376806 | ENA
Project description:Glucose-dependent insulinotropic polypeptide (GIP) has been proposed to exert insulin-independent effects on lipid and bone metabolism. We investigated the effect of a 6-day s.c. GIP infusion on circulating lipids, white adipose tissue (WAT), brown adipose tissue (BAT), hepatic fat content, and inflammatory markers in patients with type 1 diabetes. In a randomized, placebo-controlled, double-blind, crossover study, 20 men with type 1 diabetes underwent a 6-day continuous s.c. infusion with GIP (6 pmol/kg/min) and placebo (saline), with an interposed seven-day washout period. Each intervention period involved three study days: Day 0 (baseline measurements, a baseline abdominal adipose tissue biopsy and blood sampling), Day 1 (fasting blood sample after 24 hours infusion), and Day 6 (fasting blood sample, an abdominal adipose tissue biopsy).
2022-11-08 | PXD034803 | Pride
Project description:A chemopreventive effect of aspirin (ASA) on lung cancer risk is supported by epidemiologic and preclinical studies. We conducted a randomized, double-blind, placebo controlled study in current heavy smokers to compare modulating effects of intermittent versus continuous low dose ASA on gene signatures of smoking and lung cancer from nasal brushings. Fifty-four participants were randomized to intermittent ASA (ASA 81 mg daily for one week alternating with placebo daily for one week) or continuous ASA (81 mg daily) for 12 weeks. The primary endpoint was modulation of a smoking gene signature in nasal brushings. Other [JB1] endpoints included modulation of nasal and bronchial gene signatures for smoking, lung cancer and chronic obstructive pulmonary disease (COPD) and changes in cyclooxygenase (COX)- and 5-lipoxygenase (LOX)-mediated arachidonic acid (ARA) metabolism. Low dose ASA intervention caused minimal changes in smoking and lung cancer gene signature scores in nasal epithelium of current heavy smokers. The small sample size of the intervention groups may have limited the ability to detect modulation of the gene signatures. Low dose ASA lowered urinary prostaglandin E metabolite, a marker of COX-mediated ARA metabolic pathway with no change in urinary leukotriene E4, a marker of 5-LOX-mediated pathway. Exploratory genomic analysis showed that ASA intervention induced wide-ranging genomic changes in the nasal epithelium, including modulation of the arachidonic acid pathway and wound healing. A companion study is underway using ASA plus zileuton to test dual suppression of COX- and 5-LOX-mediated pathways on these gene signature scores in current heavy smokers.
2019-12-24 | GSE124637 | GEO
Project description:Wistar rats, male, treated with 500 mg/Kg/day of diacetyl by gavage, during 4 weeks
2018-04-18 | PXD004504 | Pride
Project description:Impact of protein ingestion following 1 h intense cycling on the induced transcriptome and signaling in biopsy samples from endurance-trained men, relative to isocaloric control Single blind, randomized, crossover design comprising two experimental blocks. During the blocks, exercise and diet were controlled and the intervention consisted of the ingestion of a protein-enriched and control beverage, with outcome measures obtained from skeletal muscle tissue collected following a bout of intense cycling. Total RNA were obtained from quadriceps. Each of the two serves were isocaloric and provided 0.2 g/kg fat (freeze dried canola oil) with either 1.2 g/kg carbohydrate (1:1 maltodextrin:fructose) and 0.4 g/kg protein (2:1 milk protein concentrate:whey isolate); or 1.6 g/kg carbohydrate (1:1 maltodextrin:fructose).
2011-11-21 | E-GEOD-27285 | biostudies-arrayexpress
Project description:Toxicogenomics (tgx) is used as a tool to identify mechanisms and markers of steatosis in C57BL/6 mice treated by oral gavage using amiodarone (AMD), valproic acid (VPA), and tetracycline (TET). Critical doses for tgx analysis were derived from a 25 day dose range finding study. For tgx analysis, livers of mice were collected after 1, 4, and 11 days of repeated treatment with 6.7, 20, and 60 mg/kg bw for AMD; 125, 250, and 500 mg/kg bw for VPA; and 14.8, 44, and 133 mg/kg bw for TET.
2014-02-25 | GSE48126 | GEO
Project description:In this study we investigated whether nicotinamide mononucleotide (NMN) could protect against Doxorubicin-induced cardiotoxicity and physical dysfunction in vivo. To assess the short- and long-term toxicity, two Doxo regimens were tested, acute and chronic. In the acute study, C57BL6/J (B6) mice were injected intraperitoneally (i.p.) once with Doxo (20 mg/kg) and NMN (180 mg/kg/day, i.p.) was administered daily for five days before and after the Doxo injection. In the chronic study, B6 mice received a cumulative dose of 20 mg/kg Doxo administered in fractionated doses for five days. NMN (500 mg/kg/day) was supplied in the mice’s drinking water beginning five days before the first injection of Doxo and continuing for 60 days after.
2023-01-11 | GSE221003 | GEO
Project description:The effect of IV-administered Vitamin C on the plasma proteome in the pig trauma model was investigated with label free proteomics. Plasma samples were drawn from 9 male Sinclair swine at baseline, post-trauma, and 0.25, 2, and 4 hours post resuscitation with 500 mL of hydroxyethyl starch. Swine were randomized to receive either saline, low-dose VitC (50 mg/kg), or high-dose VitC (200 mg/kg) during volume resuscitation (N = 3/treatment). High performance LC-MS/MS proteomics was then used to quantitatively measure plasma protein levels over time.
2019-07-29 | PXD012454 | Pride
Project description:The effect of IV-adminstered Vitamin C on the plasma proteome in the pig trauma model was investigated with label free proteomics. Plasma samples were drawn from 9 male Sinclair swine at baseline, post-trauma, and 0.25, 2, and 4 hourspost resuscitation with 500 mL of hydroxyethyl starch. Swine were randomized to receive either saline, low-dose VitC (50 mg/kg), or high-dose VitC (200 mg/kg) during volume resuscitation (N = 3/treatment). High performance LC-MS/MS proteomics was then used to quantitatively measure plasma protein fluctations over time as a function of treatment.
2022-03-11 | PXD010608 | Pride