Trial of Oral Glutamine in Patients With Sickle Cell Anemia

Study Overview
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Brief Summary
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Children with sickle cell anemia (SCA) seem to have higher energy needs than children who do not have the disease. This may be the reason why children and teenagers with sickle cell anemia tend to be smaller, weigh less, and have less fat and muscle than children and teens that do not have the disease. This study is being done to find out if giving a supplement called glutamine will help children with sickle cell anemia by lowering their energy needs and improving their growth and strength. Children will be randomly assigned (like a flip of a coin) to one of two groups. One group will take glutamine and one group will take a placebo (a protein mixture that looks like glutamine but may not have the same effect in the body). No one will know which group is taking which supplement until the study has been completed. Children will be in the study for 12 months.

Detailed Description
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The study will compare the effect of glutamine and placebo on resting energy expenditure (REE) in children with sickle cell anemia (SCA) by comparing the change in REE ratio between baseline and 12 months. The study investigates the effect of oral glutamine and placebo on body composition in children with SCA by comparing the difference in body mass indexes (BMIs) and percent of body fat (DEXA Scan) between baseline and 12 months of treatment in the two groups. This Study will investigate the effect of oral glutamine and placebo on growth in children with SCA by comparing the Z scores for one year before baseline to 1 year while on study. This study will investigate the effect of oral glutamine and placebo in children with SCA by comparing the difference in the levels of plasma and red blood cell glutamine between baseline and 12 months of treatment in the two groups. This study will investigate the clinical effects (strength and exercise endurance) of oral glutamine and placebo in children with SCA by comparing the difference between baseline and 12 months of treatment in the two groups. This study will evaluate quality of life in children with SCA who have glutamine or placebo for 12 months. This study will evaluate the changes in REE over time in a small group of patients that will have REE measurement at months 3, 6, and 9. This objective will be offered to all patients, but will be additional studies that are not required to participate in the protocol.

Official Title
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A Randomized Controlled Trial of Oral Glutamine Supplementation Versus a Placebo Supplement in Children With Sickle Cell Anemia

Conditions
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Anemia, Sickle Cell

Intervention / Treatment
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* Drug: Glutamine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Active patient (presently receiving medical care for SCA) at the St. Jude Comprehensive Sickle Cell Center (SJCSCC) or an affiliate or alliance of St Jude. Patient must not be in the high risk category as defined by the SJCSCC. High risk is defined as follows: 3 or more admissions and/or emergency department visits for pain within the past 12 months, or; 2 or more episodes of acute chest syndrome within the past 24 months, or; A combination of pain and ACS events > 3 within the past 12 months. 5-18 years of age Diagnosis of Hb SS or HB0Thal Weight >15 kg <50th percentile for height/age or weight/age or weight/ height, or <90% ideal body weight, or <90% of BMI for age/ gender. Is willing to sign informed consent Exclusion Criteria Patients receiving hydroxyurea or any other anti-sickling agent, chronic transfusion, or nutrition supplements.A nutrition supplement is any high calorie or high protein food additive or oral supplement being used for the purpose of weight gain. History of poor compliance (Missing two or more clinic appointments in the past year). Renal or liver dysfunction Renal dysfunction as defined by serum creatinine >1.5 times normal for age based on testing lab. Hepatic dysfunction as defined by alanine aminotransferase (ALT) >2 times the upper limit of normal for age based on testing lab. Breastfeeding Pregnancy.Females of childbearing potential must have negative serum or urine pregnancy test (record date of test). Patients enrolled on previous glutamine protocol (SCDGLU). Patients who are considered high risk

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 2<br>Glutamine | Drug: Glutamine<br>* 0.6 gm/kg of oral glutamine per day, in two doses for one year.<br>|
| Placebo Comparator: 1<br> | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Resting Energy Expenditure From Baseline to 12 Months | To compare the effect of glutamine and placebo on resting energy expenditure (REE) in children with sickle cell anemia (SCA) by comparing the change in REE ratio between baseline and 12 months. REE was measured by indirect calorimetry, using a metabolic cart.REE Ratio =(REE Measured/REE Predicted)x 100).Change was defined as 12 Month REE Ratio minus Baseline REE Ratio.The REE Ratio was evaluated at baseline and 12 months.The REE Ratio is calculated as (REE Measured / REE Predicted) x 100).REE units are measured as (Kcal / day).Change was defined as 12 Month REE Ratio minus Baseline REE Ratio. | Baseline and 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Body Mass Index From Baseline to 12 Months | To investigate the effect of oral glutamine and placebo on body composition in children with SCA by comparing the difference in body mass indexes (BMI) between baseline and 12 months of treatment in the two groups. | Baseline and 12 months | 
| Change in Red Blood Cell Glutamine From Baseline to 12 Months | To investigate the effect of oral glutamine and placebo in children with Sickle Cell Anemia (SCA) by comparing the difference in the levels of red blood cell glutamine between baseline and 12 months of treatment in the two groups. | Baseline and 12 months | 
| Change in Quality of Life Measures From Baseline to 12 Months.Scores for Each Subcategory Range From 0 (Best) to 4 (Worst).This is True for Both Patient and Parent Reports. | Evaluation of quality of life at baseline and 12 months in the glutamine versus placebo group using the PedsQL Version 4.0 inventory. This instrument measures individual well being across physical, emotional, social, and school function categories using patient self-reports and/or parent reports. The tool contains a 15-question, age-specific, self-report inventory (for children age 5-7 years, 8-12 years, and 13-18 years) and a corresponding parent inventory. Lower scores indicate a better quality of life. | Baseline and 12 Months | 
| Change in Height Z-score From Baseline to 12 Months | To investigate the effect of oral glutamine and placebo on height Z-score in children with Sickle Cell Anemia (SCA) between baseline and 12 months on treatment. | Baseline and 12 months | 
| Change in Height Percentile From Baseline to 12 Months | To investigate the effect of oral glutamine and placebo on height percentile in children with Sickle Cell Anemia (SCA) between baseline and 12 months on treatment. | Baseline and 12 months | 
| Change in Weight Percentile From Baseline to 12 Months | To investigate the effect of oral glutamine and placebo on weight in children with Sickle Cell Anemia (SCA) between baseline and 12 months on treatment. | Basline and 12 months | 
| Change in Pulse Rate From Baseline to 12 Months | To investigate the clinical effects of oral glutamine and placebo on pulse rate in children with Sickle Cell Anemia (SCA) by comparing the difference between baseline and 12 months of treatment between the two groups. | Baseline and 12 months | 
| Change in Hand Grip From Baseline to 12 Months. | To investigate the clinical effects of oral glutamine and placebo on hand grip in children with Sickle Cell Anemia (SCA) by comparing the difference between baseline and 12 months of treatment between the two groups. Hand grip strength is a measure of muscle strength.Units are measured in Kg.Muscle strength is measured using a hydraulic hand-held dynamometer.Change was defined as 12 Month measure minus baseline.Muscle strength is measured using the hand grip strength via a hydraulic hand-held dynamometer (Kg). | Baseline and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hemoglobin S Disease, Sickle Cell Anemia