Glutamine Therapy for Hemolysis-Associated Pulmonary Hypertension

Sickle Cell Disease Clinical Trial

Official title:

Phase 2 Trial for Glutamine Therapy for Hemolysis-Associated Pulmonary Hypertension

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01048905
• Other study ID #: 1R01FD003531-01
• Secondary ID: IRB 2008-0591R01
• Status: Completed
• Phase: Phase 2
• Start date: March 2009
• Est. completion date: March 2014

Study information

• Verified date: June 2021
• Source: UCSF Benioff Children's Hospital Oakland
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: March 2014
• Est. primary completion date: March 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 4 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Hemolysis
• Hypertension
• Hypertension, Pulmonary
• Pulmonary Hypertension
• Sickle Cell Disease
• Thalassemia

Intervention

Drug:
• L-Glutamine
Oral L-glutamine 10 grams TID or (0.1g/kg TID) for children < 15 years of age.

Locations

Country	Name	City	State
United States	Children's Hospital & Research Center Oakland	Oakland	California

Sponsors (2)

Lead Sponsor	Collaborator
UCSF Benioff Children's Hospital Oakland	Food and Drug Administration (FDA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Erythrocyte Glutamine/Glutamate Ratio at 8 Weeks	Erythrocyte Glutamine/Glutamate Ratio: a novel biomarker of oxidative stress	8 weeks
Secondary	Plasma Glutamine		8 weeks
Secondary	Tricuspid Regurgitant Jet Velocity on Doppler Echocardiography	Tricuspid Regurgitant Jet Velocity was measured using Doppler Echocardiography in meters per second.	8 week
Secondary	6 Minute Walk Distance	The six-minute walk test (6MWT) measures the distance in meters an individual is able to walk over a total of six minutes on a hard, flat surface.	8 weeks
Secondary	Liver Function Tests	Alanine aminotransferase (ALT) Aspartate aminotransferase (AST)	8 weeks
Secondary	Renal Function Tests	Creatinine Blood urea nitrogen (BUN)	8 weeks