L-Glutamine Therapy for Sickle Cell Anemia

Study Overview
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Brief Summary
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The primary purpose is to evaluate the effect of L-glutamine therapy on exercise endurance and breath by breath exercise response of sickle cell anemia patients The secondary purpose is to assess the effect of L-glutamine on incidence of painful crises; level of chronic pain, and amount of daily requirement for narcotics.

Detailed Description
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This is a phase II, prospective, randomized, double-blind, placebo-controlled, parallel-group,study to evaluate the safety and efficacy of oral L-glutamine therapy for patients with sickle cell anemia or sickle β°-thalassemia who are at least 18 years old with focus on the aspect of exercise endurance. In this study, the patients will orally take L-glutamine or placebo twice daily, and clinical and hematological parameters will be monitored. The adverse events,especially those attributable to L-glutamine therapy, will also be monitored. The data obtained will be essential in understanding the role of L-glutamine in therapy for sickle cell anemia and sickle β°-thalassemia.

Official Title
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A Phase II, Prospective, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Study of L Glutamine Therapy for Sickle Cell Anemia and Sickle ß0-Thalassemia

Conditions
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Sickle Cell Anemia, Thalassemia

Intervention / Treatment
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* Drug: L-Glutamine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: To be eligible to participate in the study, a patient must meet all of the following inclusion criteria: Patient is at least 18 years of age. Patient has been diagnosed with sickle cell anemia or sickle ß0-thalassemia (documented by hemoglobin electrophoresis). Patient has had at least two episodes of painful crises within 12 months of the screening visit. If the patient has been treated with an anti-sickling agent within three months of the screening visit, the therapy must have been continuous for at least three months with the intent to continue for the next 14 months. Patient or the patient's legally authorized representative has given written informed consent. If the patient is a female of child-bearing potential, she agrees to practice a recognized form of birth control during the course of the study. Patient is able to perform exercise tolerance test Exclusion Criteria: If the patient meets any of the following criteria, the patient must not be enrolled: Patient has a significant medical condition that required hospitalization (other than sickle painful crisis) within two months of the screening visit. Patient has diabetes mellitus with untreated fasting blood sugar >115 mg/dL. Patient has prothrombin time International Normalized Ratio (INR) > 2.0. Patient has serum albumin < 3.0 g/dl. Patient has received any blood products within three weeks of the screening visit. Patient has a history of uncontrolled liver disease or renal insufficiency. Patient is pregnant or lactating. Patient has been treated with an experimental anti-sickling medication/treatment (except hydroxyurea) within 30 days of the screening visit. Patient has been treated with an experimental drug within 30 days of the screening visit. There are factors that would, in the judgment of the investigator, make it difficult for the patient to comply with the requirements of the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: L-glutamine<br>L-glutamine group will be given at the following dosage: 17-33.3 kg at 5 g 2x daily 33.4-66.6 kg at 10 g 2X daily >66.7 at 15 g 2X daily | Drug: L-Glutamine<br>* L-Glutamine at: 5 g 2X daily (17-33.3 Kg) 10 g 2x daily (33.4-66.6 Kg) 15 g 2x daily (>66.7 kg)<br>|
| Placebo Comparator: Placebo<br>Maltodextrin group will be given at the following dosage: 17-33.3 kg at 5 g 2x daily 33.4-66.6 kg at 10 g 2X daily >66.7 at 15 g 2X daily | Drug: Placebo<br>* Placebo (75% Maltodextrin, 24.5 % Starch, 0.5% Tricalcium Phosphate) - given at the same dosage as L-glutamine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of L-glutamine Therapy on Exercise Endurance of Sickle Cell Anemia Patients | Exercise endurance will be examined at each visit. Change from baseline will be reported at weeks 8 and 12 | Baseline, Weeks 8 and 12 | 
| Effect of L-glutamine Therapy on Breath by Breath Exercise of Sickle Cell Patients | Breath by breath exercise will be examined at each visit. Change from baseline will be reported at weeks 8 and 12 | Baseline, Weeks 18 and 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of Oral L-glutamine on Incidence of Painful Crises | Incidence of panful crises will be assessed at each visit. | From Week 0 through Week 12 | 
| Effect of Oral L-glutamine on Amount of Daily Requirement for Narcotics | Amount of daily requirement for narcotics will assessed at each visit. | From Week 0 through Week 20 | 
| Effect of Oral L-glutamine on Level of Chronic Pain | Level of chronic pain will be assessed at each visit. | From Week 0 to Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sickle cell disease, sickle cell anemia, L-glutamine, Sickle Cell Anemia (homozygous), Sickle β°-Thalassemia