Glutamine Therapy for Hemolysis-Associated Pulmonary Hypertension

Phase 2

Completed

• Conditions: Pulmonary Hypertension; Sickle Cell Disease; Thalassemia
• Interventions: Drug: L-Glutamine

• Registration Number: NCT01048905
• Lead Sponsor: UCSF Benioff Children's Hospital Oakland

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 available

Study Timeline

• Study Start: 2009-03
• Study First Submitted: 2010-01-12
• Study First Submitted QC: 2010-01-13
• Study First Posted: 2010-01-14
• Primary Completion: 2014-03
• Study Completion: 2014-03
• Results First Submitted: 2021-04-20
• Status Verified: 2021-06
• Results First Submitted QC: 2021-06-08
• Last Update Submitted: 2021-06-08
• Results First Posted: 2021-06-10
• Last Update Posted: 2021-06-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 13

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment: L-glutamine	L-Glutamine	Patients will receive an 8-week course of oral L-glutamine 10 grams TID

Primary Outcome Measures

Name	Time	Method
Erythrocyte Glutamine/Glutamate Ratio at 8 Weeks	8 weeks	Erythrocyte Glutamine/Glutamate Ratio: a novel biomarker of oxidative stress

Secondary Outcome Measures

Name	Time	Method
Plasma Glutamine	8 weeks
6 Minute Walk Distance	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	8 weeks	Alanine aminotransferase (ALT) Aspartate aminotransferase (AST)
Renal Function Tests	8 weeks	Creatinine Blood urea nitrogen (BUN)
Tricuspid Regurgitant Jet Velocity on Doppler Echocardiography	8 week	Tricuspid Regurgitant Jet Velocity was measured using Doppler Echocardiography in meters per second.

Trial Locations

Locations (1)

Children's Hospital & Research Center Oakland; 🇺🇸 Oakland, California, United States