Glutamine Therapy for Hemolysis-Associated Pulmonary Hypertension

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

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 Overview

• Status: Completed
• Conditions: Sickle Cell Disease; Pulmonary Hypertension; Thalassemia
• Intervention / Treatment: Drug: L-Glutamine

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Oakland, California, United States, 94608
      • Children's Hospital & Research Center Oakland

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment: L-glutamine; Patients will receive an 8-week course of oral L-glutamine 10 grams TID	Drug: L-Glutamine; Oral L-glutamine 10 grams TID or (0.1g/kg TID) for children < 15 years of age.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Erythrocyte Glutamine/Glutamate Ratio at 8 Weeks	Erythrocyte Glutamine/Glutamate Ratio: a novel biomarker of oxidative stress	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Glutamine		8 weeks
Tricuspid Regurgitant Jet Velocity on Doppler Echocardiography	Tricuspid Regurgitant Jet Velocity was measured using Doppler Echocardiography in meters per second.	8 week
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
Liver Function Tests	Alanine aminotransferase (ALT) Aspartate aminotransferase (AST)	8 weeks
Renal Function Tests	Creatinine Blood urea nitrogen (BUN)	8 weeks

Collaborators and Investigators

• Sponsor: UCSF Benioff Children's Hospital Oakland
• Collaborators: Food and Drug Administration (FDA)
• Investigators: Principal Investigator: Claudia Morris, MD, Emory University; Principal Investigator: Augusta Saulys, MD, Children's Hosptial & Research Center Oakland

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): March 1, 2014
• Study Completion (Actual): March 1, 2014

Study Registration Dates

• First Submitted: January 12, 2010
• First Submitted That Met QC Criteria: January 13, 2010
• First Posted (Estimate): January 14, 2010

Study Record Updates

• Last Update Posted (Actual): June 10, 2021
• Last Update Submitted That Met QC Criteria: June 8, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Pulmonary Hypertension; Thalassemia; Sickle Cell Disease
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Hypertension; Anemia, Sickle Cell; Hypertension, Pulmonary; Thalassemia; Hemolysis
• Other Study ID Numbers: 1R01FD003531-01 (U.S. FDA Grant/Contract); IRB 2008-059 (Other Identifier: Institutional Review Board)