L-Glutamine Therapy for Sickle Cell Anemia and Sickle ß0 Thalassemia

Study Overview
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Brief Summary
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The purpose of this research is to evaluate the effects of L-glutamine as a therapy for sickle cell anemia and sickle ß0-thalassemia. as evaluated by the number of occurrences of sickle cell crises.

Detailed Description
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The primary purpose of this study is to evaluate the effectiveness of oral L-glutamine in the therapy of sickle cell anemia and sickle ß0-thalassemia. The secondary purpose is to assess the effect of L-glutamine frequency of hospitalizations for sickle cell pain, frequency of emergency room visits for sickle cell pain; energy and appetite levels; narcotics usage. Methodology: By site, patients will be randomized to L-glutamine or placebo in a 1:1 ratio after a 4-week screening period. Patients will undergo 48 weeks of treatment with dosing BID orally, with dose calculated according to patient weight. Patient visits will occur every 4 weeks. After 48 weeks of treatment, dose will be tapered to zero within 3 weeks. A final evaluation visit will occur 2 weeks after last dose.

Official Title
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A Phase II, Prospective, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter 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 five 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. 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: 5 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: investigational product<br>L-glutamine | Drug: L-glutamine<br>* Approximately 0.3 g/kg total daily dose of L-glutamine will be orally administered (over two doses), with a maximum total daily dose of 30 grams.<br>* Other names: oral L-glutamine;|
| Placebo Comparator: placebo<br>maltodextrin | Drug: Placebo<br>* Approximately 0.3 g/kg total daily dose of maltodextrin placebo will be orally administered (over two doses), with a maximum total daily dose of 30 grams.<br>* Other names: maltodextrin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Occurrences of Painful Sickle Cell Crises | The mean number of painful sickle crisis through week 48 | From Week 0 through Week 48 (cumulative) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of Hospitalizations for Sickle Cell Pain | The mean number of hospitalizations through week 48 | From Week 0 through Week 48 (cumulative) | 
| Frequency of Emergency Room Visits for Sickle Cell Pain | The mean number of emergency room visits through week 48 | From Week 0 through Week 48 (cumulative) | 
| The Effect of Oral L-glutamine on Hematological Parameters - Hemoglobin | Patient's hemoglobin will be collected at each visit.Change from Baseline will be reported at Weeks 4, 24 and 40. | Baseline, Weeks 4, 24 and 40 | 
| The Effect of Oral L-glutamine on Hematological Parameters - Hematocrit | Patient's hematocrit will be collected at each visit. Change from Baseline will be reported at Weeks 4, 24 and 40 | Baseline, Weeks 4, 24, and 40 | 
| The Effect of Oral L-glutamine on Hematological Parameters - Reticulocyte Count | Patient's reticulocyte count will be collected at each visit. Change from Baseline will be reported at Weeks 4, 24 and 40 | Baseline, Weeks 0, 4, 24, 40 | 
| Number of Participants With Narcotic Usage | Analysis of narcotic usage was performed for the subset of patients with any narcotic use who completed the study. Changes in narcotic usage were determined by an independent consultant prior to database lock using morphine equivalents to determine relative use. | Week 24, Week 48 | 
| Energy Level (11-point Scale) | The patient's energy level was evaluated at each visit using an 11 point scale from 0=extremely tired to 10=extremely energetic | Collected at Week 0, 8, 16, 24, 32, 40, 48 | 
| Patient Appetite (3-point Scale) | Patient's appetite level was evaluated at each visit using a 3 point scale: above average, average and below average. The parentages of patient at each visit whose appetite level was below, normal or above average were compared using CMH test (row mean scores) controlling for study center. | Collected at Week 0, 8, 16, 24, 32, 40, 48 | 
| The Effect of Oral L-glutamine on Vital Signs - Blood Pressure | Patient's blood pressure will be collected at each visit. Change from Baseline will be reported at Weeks 4, 24, and 48 | Baseline, Weeks 4, 24, and 48 | 
| The Effect of Oral L-glutamine on Vital Signs - Temperature | Patient's temperature will be collected at each visit. Change from Baseline will be reported at Weeks 4, 24, and 48 | Baseline, Weeks 4, 24, and 48 | 
| The Effect of Oral L-glutamine on Vital Signs - Respiration | Respiration will be collected at each visit. Change from Baseline will be reported at Weeks 4, 24, and 48 | Baseline, Weeks 4, 24, and 48 | 
| The Effect of Oral L-glutamine on Vital Signs - Pulse Rate | Patient's pulse rate will be collected at each visit, Change from Baseline will be reported at Weeks 4, 24, and 48 | Baseline, Weeks 4, 24, and 48 | 
| Effect of L-glutamine on Alcohol Use | The patient's alcohol usage will be assessed at each visit. Alcohol usage will be reported at Weeks 0, 8,16, 24, 32, 40 and 48 | Weeks 0, 8,16, 24, 32, 40 and 48 | 
| Effect of L-glutamine on Tobacco Use | Patient's alcohol usage will be assessed at each visit. Alcohol usage will be reported at Weeks 0, 8,16, 24, 32, 40 and 48 | Weeks 0, 8,16, 24, 32, 40 and 48 | 
| The Effect of Oral L-glutamine on the Number of Days Patient's Daily Activities Are Interrupted Due to Sickle Cell Pain | Percentage of days a patient's daily activities were interrupted due to sickle pain calculated at each visit. Day's interrupted will be reported at Weeks 0, 8,16, 24, 32, 40 and 48 | Weeks 0, 8,16, 24, 32, 40 and 48 | 
| The Effect of Oral L-glutamine on Subjective Quality of Life | The subjective quality of life was evaluated using the scoring of the RAND 36-Item Health Survey Questionnaire. The subjective quality of life (Physical functioning, Physical health, Emotional problems, Energy/Fatigue, Emotional well being, Social functioning, Pain, General health) will be reported at Baseline and Week 24 (or at time of discontinuation). The range for Physical functioning, Physical health, Emotional problems, Emotional well being and Social functioning is 0-100, with a high score denotes a better quality of life. For Energy/Fatigue, Pain and General health the range is 0-100, with a lower score denotes better quality of life. | Baseline and Week 24 (or at time of discontinuation) | 
| Effect of Oral L--glutamine on Height | Height will be measured at each visit. Change from Baseline will be reported at Weeks 4, 24, and 48 | Baseline, Weeks 4, 24, and 48 | 
| Effect of Oral L--glutamine on Weight | Weight will be measured at each visit. Change from Baseline will be reported at Weeks 4, 24, and 48 | Baseline, Weeks 4, 24 and 48 | 
| Effect of L-glutamine on Subjective Exercise Tolerance - Minutes Patient Could Walk Without Rest | Minutes patient could walk without rest will be measured at each visit. Change from Baseline will be reported at Weeks 4, 24, and 48. | Baseline, Weeks 4, 24, and 48. | 
| Effect of L-glutamine on Subjective Exercise Tolerance - Minutes Patient Could Run Without Rest | Minutes patient could run without rest will be measured at each visit. Change from Baseline will be reported at Weeks 4, 24, and 48. | Baseline, Weeks 4, 24, and 48. | 
| Effect of L-glutamine on Subjective Exercise Tolerance - Distance Patient Could Walk Without Rest | Distance patient could walk without rest will be collected at each visit. Change from Baseline will be reported at Weeks 4, 24, and 48. | Baseline, Weeks 4, 24, and 48. | 
| Effect of L-glutamine on Subjective Exercise Tolerance - Distance Patient Could Run Without Rest | Distance patient could run without rest will be collected at each visit. Change from Baseline will be reported at Weeks 4, 24, and 48. | Baseline, Weeks 4, 24, and 48. | 

 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 ß0-Thalassemia