Glutamine Therapy for Hemolysis-Associated Pulmonary Hypertension

NCT01048905 | Completed Phase 2 Results DMC

• 2 other identifiers: 1R01FD003531-01IRB 2008-059
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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.

Conditions

Pulmonary Hypertension; Sickle Cell Disease; Thalassemia

Keywords

Pulmonary Hypertension; Sickle Cell Disease; Thalassemia

Outcome Measures

Primary Outcomes (1)

• Erythrocyte Glutamine/Glutamate Ratio at 8 Weeks

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

  8 weeks

Secondary Outcomes (5)

• Plasma Glutamine

  8 weeks

• Tricuspid Regurgitant Jet Velocity on Doppler Echocardiography

  8 week

• 6 Minute Walk Distance

  8 weeks

• Liver Function Tests

  8 weeks

• Renal Function Tests

  8 weeks

Study Arms (1)

Treatment: L-glutamine

EXPERIMENTAL

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

Drug: L-Glutamine

Interventions

L-Glutamine DRUG

Oral L-glutamine 10 grams TID or (0.1g/kg TID) for children \< 15 years of age.

Treatment: L-glutamine

Eligibility Criteria

• Age: 4 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• UCSF Benioff Children's Hospital Oakland: lead
• Food and Drug Administration (FDA): collaborator

Study Sites (1)

Children's Hospital & Research Center Oakland

Oakland, California, 94608, United States

Location

MeSH Terms

Conditions

Hypertension, Pulmonary; Anemia, Sickle Cell; Thalassemia

Interventions

Glutamine

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Neutral

Results Point of Contact

• Title: Claudia R. Morris MD, FAAP
• Organization: Emory University School of Medicine

claudia.r.morris@emory.edu

404-727-5500

Study Officials

• Claudia Morris, MD

  Emory University

  PRINCIPAL INVESTIGATOR

• Augusta Saulys, MD

  Children's Hosptial & Research Center Oakland

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 12, 2010
• First Posted: January 14, 2010
• Study Start: March 1, 2009
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: June 10, 2021
• Results First Posted: June 10, 2021

Record last verified: 2021-06

Locations

US (1)