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Glutamine Therapy for Hemolysis-Associated Pulmonary Hypertension

This study is currently recruiting participants.
Verified January 2013 by Children's Hospital & Research Center Oakland
Sponsor:
Information provided by (Responsible Party):
Children's Hospital & Research Center Oakland
ClinicalTrials.gov Identifier:
NCT01048905
First received: January 12, 2010
Last updated: January 2, 2013
Last verified: January 2013
History of Changes
  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:

Drug Information available for: Glutamine
U.S. FDA Resources

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, hemolysis and PH post therapy compared to pre-therapy steady-state values. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: March 2009
Estimated Study Completion Date: March 2013
Estimated Primary Completion Date: March 2013 (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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01048905

Contacts
Contact: Melinee Stewart 510-428-3885 ext 2858 Mstewart@mail.cho.org
Contact: Lisa Lavrisha, NP 510-428-3885 ext 4376 LLavrisha@mail.cho.org

Locations
United States, California
Children's Hospital & Research Center Oakland Recruiting
Oakland, California, United States, 94608
Contact: Melinee Stewart     510-428-3885 ext 2858     Mstewart@mail.cho.org    
Contact: Lisa Lavrisha         LLavrisha@mail.cho.org    
Sub-Investigator: Elliott Vichinsky, MD            
Sub-Investigator: Frans Kuypers, PhD            
Sub-Investigator: Jung Suh, PhD            
Sub-Investigator: Mark Gladwin, MD            
Sub-Investigator: Greg Kato, MD            
Principal Investigator: Augusta Saulys, MD            
Sub-Investigator: Ward Hagar, MD            
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: January 2, 2013
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:
Anemia, Sickle Cell
Hemolysis
Hypertension
Hypertension, Pulmonary
Thalassemia
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
 Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Pathologic Processes
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on May 21, 2013