Glutamine Therapy for Hemolysis-Associated Pulmonary Hypertension
Summary
The primary hypothesis of this study is that glutamine supplementation will improve the erythrocyte glutamine/glutamate ratio, a biomarker of oxidative stress, hemolysis and pulmonary hypertension (PH) in sickle cell disease (SCD) and thalassemia (Thal) patients with PH. PH is defined as a tricuspid regurgitant jet velocity (TRV) on Doppler echocardiography > 2.5 m/s. We also predict that glutamine therapy will increase arginine bioavailability and subsequently alter sickle red cell endothelial interaction that can be identified using endo-PAT technology through nitric oxide (NO) generation, leading to changes in biological markers, and clinical outcome. Specifically our second hypothesis is that oral glutamine will decrease biomarkers of hemolysis and adhesion molecules, and improve the imbalanced arginine-to-ornithine ratio that occurs in hemolytic anemias, leading to improved arginine bioavailability and clinical endpoints of endothelial dysfunction and PH in patients with SCD and Thal.
Study Design
Allocation: Non-Randomized, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Treatment
Conditions
Pulmonary Hypertension
Intervention
L-Glutamine, L-Glutamine
Location
Children's Hospital & Research Center Oakland
Oakland
California
United States
94608
Status
Recruiting
Source
Children's Hospital & Research Center Oakland
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT01048905
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Carbon-nitrogen Ligases With Glutamine As Amide-n-donor
Enzymes that catalyze the joining of glutamine-derived ammonia and another molecule. The linkage is in the form of a carbon-nitrogen bond. EC 6.3.5.
Glutamine-fructose-6-phosphate Transaminase (isomerizing)
An enzyme that catalyzes the synthesis of fructose-6-phosphate plus GLUTAMINE from GLUTAMATE plus glucosamine-6-phosphate.
Carbamoyl-phosphate Synthase (glutamine-hydrolyzing)
An enzyme that catalyzes the formation of carbamoyl phosphate from ATP, carbon dioxide, and glutamine. This enzyme is important in the de novo biosynthesis of pyrimidines. EC 6.3.5.5.
Pulmonary Heart Disease
Hypertrophy and dilation of the RIGHT VENTRICLE of the heart that is caused by PULMONARY HYPERTENSION. This condition is often associated with pulmonary parenchymal or vascular diseases, such as CHRONIC OBSTRUCTIVE PULMONARY DISEASE and PULMONARY EMBOLISM.
Epoprostenol
A prostaglandin that is a powerful vasodilator and inhibits platelet aggregation. It is biosynthesized enzymatically from PROSTAGLANDIN ENDOPEROXIDES in human vascular tissue. The sodium salt has been also used to treat primary pulmonary hypertension (HYPERTENSION, PULMONARY).
Clinical Trials
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The Effect of Glutamine on Systemic Inflammation During Human Experimental Endotoxemia
Glutamine levels decrease during severe sepsis; this may be associated with increased mortality. The investigators tested the effects of glutamine supplementation on systemic inflammation...
Glutamine and Intestinal Protein Metabolism
Gut barrier plays a major role in defence of the organism. During catabolic states, like major surgery or inflammation, gut barrier could be altered. It has been reported that preoperative...
Glutamine in Preventing Acute Diarrhea in Patients With Pelvic Cancer
RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Glutamine may be an effective treatment for acute diarrhea caused by radiation therapy. It is not known if gluta...
The investigators hypothesize that glutamine significantly reduces the incidence and severity of peripheral neuropathy in patients receiving oxaliplatin for metastatic colorectal cancer, d...
PubMed Articles
Glutamine stimulates mTORC1 independent of the cell content of essential amino acids.
Glutamine and leucine are important mTORC1 modulators, although their roles are not precisely defined. In HepG2 and HeLa cells glutamine-free incubation lowers mTORC1 activity, although cell leucine i...
Hydrogen bonding between glutamine residues has been identified as playing an important role in the intermolecular association and aggregation of proteins. To establish the molecular mechanisms of glu...
Activation of a naive T cell is a highly energetic event, which requires a substantial increase in nutrient metabolism. Upon stimulation, T cells increase in size, rapidly proliferate, and differentia...
For most cultivated mammalian cells, glutamine is an essential medium component. However, glutamine consumption results in the production of ammonia, a cytotoxic byproduct. Here we investigated the ef...
The Bacillus subtilis glutamine synthetase (GS) plays a dual role in cell metabolism by functioning as catalyst and regulator. GS catalyses the ATP-dependent synthesis of glutamine from glutamate and...
