Glutamine Therapy for Hemolysis-Associated Pulmonary Hypertension

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Children's Hospital & Research Center Oakland
ClinicalTrials.gov Identifier:
NCT01048905
First received: January 12, 2010
Last updated: July 17, 2014
Last verified: July 2014
  Purpose

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 Intervention Phase
Pulmonary Hypertension
Sickle Cell Disease
Thalassemia
Drug: L-Glutamine
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 2 Trial for Glutamine Therapy for Hemolysis-Associated Pulmonary Hypertension

Resource links provided by NLM:


Further study details as provided by Children's Hospital & Research Center Oakland:

Primary Outcome Measures:
  • Change in erythrocyte glutamine/glutamate ratio, a novel biomarker of oxidative stress,post therapy compared to pre-therapy steady-state values. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Plasma Glutamine [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Tricuspid Regurgitant Jet velocity on Doppler Echocardiography [ Time Frame: 8 week ] [ Designated as safety issue: No ]
  • 6 minute walk distance [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Liver function tests [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
  • Renal function tests [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 32
Study Start Date: March 2009
Study Completion Date: March 2014
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pharmacokinetics
8 hour pharmacokinetics after glutamine supplementation
Drug: L-Glutamine
Oral L-glutamine 10 grams TID or (0.1g/kg TID) for children < 15 years of age.
Experimental: Treatment
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.

  Eligibility

Ages Eligible for Study:   4 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01048905

Locations
United States, California
Children's Hospital & Research Center Oakland
Oakland, California, United States, 94608
Sponsors and Collaborators
Children's Hospital & Research Center Oakland
Investigators
Principal Investigator: Claudia Morris, MD Emory University
Principal Investigator: Augusta Saulys, MD Children's Hosptial & Research Center Oakland
  More Information

No publications provided

Responsible Party: Children's Hospital & Research Center Oakland
ClinicalTrials.gov Identifier: NCT01048905     History of Changes
Other Study ID Numbers: 1R01FD003531-01, IRB 2008-059
Study First Received: January 12, 2010
Last Updated: July 17, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Children's Hospital & Research Center Oakland:
Pulmonary Hypertension
Sickle Cell Disease
Thalassemia

Additional relevant MeSH terms:
Hypertension
Hypertension, Pulmonary
Thalassemia
Anemia, Sickle Cell
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn

ClinicalTrials.gov processed this record on September 30, 2014