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

Tracking Information

• First Submitted Date: January 12, 2010
• First Posted Date: January 14, 2010
• Results First Submitted Date: April 20, 2021
• Results First Posted Date: June 10, 2021
• Last Update Posted Date: June 10, 2021
• Study Start Date: March 2009
• Actual Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 8, 2021)

Erythrocyte Glutamine/Glutamate Ratio at 8 Weeks [ Time Frame: 8 weeks ]

Erythrocyte Glutamine/Glutamate Ratio: a novel biomarker of oxidative stress

• Original Primary Outcome Measures (submitted: January 13, 2010): 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 ]

Current Secondary Outcome Measures (submitted: June 8, 2021)

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

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Glutamine Therapy for Hemolysis-Associated Pulmonary Hypertension
• Official Title: Phase 2 Trial for Glutamine Therapy for Hemolysis-Associated Pulmonary Hypertension
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• 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.

Study Arms

Experimental: Treatment: L-glutamine

Patients will receive an 8-week course of oral L-glutamine 10 grams TID

Intervention: Drug: L-Glutamine

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 8, 2021): 13
• Original Estimated Enrollment (submitted: January 13, 2010): 50
• Actual Study Completion Date: March 2014
• Actual Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)

Eligibility 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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 4 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: 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 )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: UCSF Benioff Children's Hospital Oakland
• Original Responsible Party: Claudia Morris, MD, Children's Hospital & Research Center Oakland
• Current Study Sponsor: UCSF Benioff Children's Hospital Oakland
• Original Study Sponsor: Same as current
• 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

• PRS Account: UCSF Benioff Children's Hospital Oakland
• Verification Date: June 2021