Clinical trial NCT01048905: Glutamine Therapy for Hemolysis-Associated Pulmonary Hypertension
Official title: Phase 2 Trial for Glutamine Therapy for Hemolysis-Associated Pulmonary Hypertension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pulmonary Hypertension
Sickle Cell Disease
Thalassemia
Keywords: Pulmonary Hypertension
Sickle Cell Disease
Thalassemia
Lead sponsor: UCSF Benioff Children's Hospital Oakland
Sponsor class: OTHER
Collaborators: name: Food and Drug Administration (FDA)
First posted: 2010-01-14
Enrollment: 13
Sex: ALL
Minimum age (years): 4
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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)

Primary outcomes:
measure: Erythrocyte Glutamine/Glutamate Ratio at 8 Weeks
timeFrame: 8 weeks
Secondary outcomes:
measure: Plasma Glutamine
timeFrame: 8 weeks
measure: Tricuspid Regurgitant Jet Velocity on Doppler Echocardiography
timeFrame: 8 week
measure: 6 Minute Walk Distance
timeFrame: 8 weeks
measure: Liver Function Tests
timeFrame: 8 weeks
measure: Renal Function Tests
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Oakland
country: United States
facility: Children's Hospital & Research Center Oakland
state: California
Study officials:
affiliation: Emory University
name: Claudia Morris, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hosptial & Research Center Oakland
name: Augusta Saulys, MD
role: PRINCIPAL_INVESTIGATOR
References: