Glutamine Therapy for Hemolysis-Associated Pulmonary Hypertension

UCSF Benioff Children's Hospital Oakland

Status and phase

Completed

Phase 2

Conditions

Thalassemia

Sickle Cell Disease

Pulmonary Hypertension

Treatments

Drug: L-Glutamine

Study type

Interventional

Funder types

Other

Other U.S. Federal agency

Identifiers

NCT01048905

IRB 2008-059 (Other Identifier)

1R01FD003531-01

Details and patient eligibility

About

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.

Enrollment

13 patients

Sex

All

Ages

4+ years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Established diagnosis of SCD (Hb SS, SC or SBeta- thalassemia) or Thal
PH documented by echocardiography, defined as at TRV greater than 2.5 m/s
Age greater than or equal to 4 years

Exclusion criteria

Inability to take or tolerate oral medication
Acute crisis or hospitalization within 1 month of enrollment
Hepatic dysfunction (SGPT greater than 3X normal)
Renal dysfunction (Creatinine greater than 2X normal)
Allergy to glutamine
Pregnancy or breastfeeding
Patients on sildenafil (Viagra), calcium channel blockers, or amino acid/protein supplements (other therapies acceptable if stable more than 3 months)