Glutamine Therapy for Hemolysis-Associated Pulmonary Hypertension

• ClinicalTrials.gov Identifier: NCT01048905
• Recruitment Status: Completed
• First Posted: January 14, 2010
• Results First Posted: June 10, 2021
• Last Update Posted: June 10, 2021
• Sponsor: UCSF Benioff Children's Hospital Oakland
• Collaborator: Food and Drug Administration (FDA)
• Information provided by (Responsible Party): UCSF Benioff Children's Hospital Oakland

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Pulmonary Hypertension; Sickle Cell Disease; Thalassemia	Drug: L-Glutamine	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 13 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 2 Trial for Glutamine Therapy for Hemolysis-Associated Pulmonary Hypertension
• Study Start Date: March 2009
• Actual Primary Completion Date: March 2014
• Actual Study Completion Date: March 2014

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Erythrocyte Glutamine/Glutamate Ratio at 8 Weeks [ Time Frame: 8 weeks ]
   Erythrocyte Glutamine/Glutamate Ratio: a novel biomarker of oxidative stress

Secondary Outcome Measures :

1. Plasma Glutamine [ Time Frame: 8 weeks ]
2. Tricuspid Regurgitant Jet Velocity on Doppler Echocardiography [ Time Frame: 8 week ]
   Tricuspid Regurgitant Jet Velocity was measured using Doppler Echocardiography in meters per second.
3. 6 Minute Walk Distance [ Time Frame: 8 weeks ]
   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.
4. Liver Function Tests [ Time Frame: 8 weeks ]
   Alanine aminotransferase (ALT) Aspartate aminotransferase (AST)
5. Renal Function Tests [ Time Frame: 8 weeks ]
   Creatinine Blood urea nitrogen (BUN)

Eligibility Criteria

• Ages Eligible for Study: 4 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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)

Contacts and Locations

Locations

United States, California

Children's Hospital & Research Center Oakland

Oakland, California, United States, 94608

Sponsors and Collaborators

UCSF Benioff Children's Hospital Oakland

Food and Drug Administration (FDA)

Investigators

• Principal Investigator: Claudia Morris, MD; Emory University
• Principal Investigator: Augusta Saulys, MD; Children's Hosptial & Research Center Oakland

More Information

• Responsible Party: UCSF Benioff Children's Hospital Oakland
• ClinicalTrials.gov Identifier: NCT01048905
• Other Study ID Numbers: 1R01FD003531-01 ( U.S. FDA Grant/Contract ); IRB 2008-059 ( Other Identifier: Institutional Review Board ); 1R01FD003531-01 ( U.S. FDA Grant/Contract )
• First Posted: January 14, 2010
• Results First Posted: June 10, 2021
• Last Update Posted: June 10, 2021
• Last Verified: June 2021

Keywords provided by UCSF Benioff Children's Hospital Oakland:

Pulmonary Hypertension; Sickle Cell Disease; Thalassemia

Additional relevant MeSH terms:

Hypertension, Pulmonary; Hypertension; Anemia, Sickle Cell; Thalassemia; Hemolysis; Vascular Diseases; Cardiovascular Diseases; Lung Diseases; Respiratory Tract Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Pathologic Processes