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

Phase 2
Completed
Conditions
Thalassemia
Sickle Cell Anemia
Interventions
Drug: Placebo
Registration Number
NCT00125788
Lead Sponsor
Emmaus Medical, Inc.
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
70
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
placeboPlacebomaltodextrin
investigational productL-glutamineL-glutamine
Primary Outcome Measures
NameTimeMethod
Number of Occurrences of Painful Sickle Cell CrisesFrom Week 0 through Week 48 (cumulative)

The mean number of painful sickle crisis through week 48

Secondary Outcome Measures
NameTimeMethod
Frequency of Hospitalizations for Sickle Cell PainFrom Week 0 through Week 48 (cumulative)

The mean number of hospitalizations through week 48

Frequency of Emergency Room Visits for Sickle Cell PainFrom Week 0 through Week 48 (cumulative)

The mean number of emergency room visits through week 48

Number of Participants With Narcotic UsageWeek 24, Week 48

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.

The Effect of Oral L-glutamine on Vital Signs - Blood PressureBaseline, Weeks 4, 24, and 48

Patient's blood pressure will be collected at each visit. Change from Baseline will be reported at Weeks 4, 24, and 48

Effect of Oral L--glutamine on HeightBaseline, Weeks 4, 24, and 48

Height will be measured at each visit. Change from Baseline will be reported at Weeks 4, 24, and 48

Effect of L-glutamine on Subjective Exercise Tolerance - Minutes Patient Could Walk Without RestBaseline, Weeks 4, 24, and 48.

Minutes patient could walk without rest will be measured at each visit. Change from Baseline will be reported at Weeks 4, 24, and 48.

Effect of L-glutamine on Subjective Exercise Tolerance - Distance Patient Could Walk Without RestBaseline, Weeks 4, 24, and 48.

Distance patient could walk without rest will be collected at each visit. Change from Baseline will be reported at Weeks 4, 24, and 48.

The Effect of Oral L-glutamine on Hematological Parameters - HemoglobinBaseline, Weeks 4, 24 and 40

Patient's hemoglobin will be collected at each visit.Change from Baseline will be reported at Weeks 4, 24 and 40.

The Effect of Oral L-glutamine on Hematological Parameters - HematocritBaseline, Weeks 4, 24, and 40

Patient's hematocrit will be collected at each visit. Change from Baseline will be reported at Weeks 4, 24 and 40

The Effect of Oral L-glutamine on Vital Signs - Pulse RateBaseline, Weeks 4, 24, and 48

Patient's pulse rate will be collected at each visit, Change from Baseline will be reported at Weeks 4, 24, and 48

Effect of L-glutamine on Alcohol UseWeeks 0, 8,16, 24, 32, 40 and 48

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

The Effect of Oral L-glutamine on the Number of Days Patient's Daily Activities Are Interrupted Due to Sickle Cell PainWeeks 0, 8,16, 24, 32, 40 and 48

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

Effect of L-glutamine on Subjective Exercise Tolerance - Minutes Patient Could Run Without RestBaseline, Weeks 4, 24, and 48.

Minutes patient could run without rest will be measured at each visit. Change from Baseline will be reported at Weeks 4, 24, and 48.

Patient Appetite (3-point Scale)Collected at Week 0, 8, 16, 24, 32, 40, 48

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.

Effect of L-glutamine on Tobacco UseWeeks 0, 8,16, 24, 32, 40 and 48

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

The Effect of Oral L-glutamine on Vital Signs - RespirationBaseline, Weeks 4, 24, and 48

Respiration will be collected at each visit. Change from Baseline will be reported at Weeks 4, 24, and 48

The Effect of Oral L-glutamine on Subjective Quality of LifeBaseline and Week 24 (or at time of discontinuation)

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.

Effect of L-glutamine on Subjective Exercise Tolerance - Distance Patient Could Run Without RestBaseline, Weeks 4, 24, and 48.

Distance patient could run without rest will be collected at each visit. Change from Baseline will be reported at Weeks 4, 24, and 48.

The Effect of Oral L-glutamine on Hematological Parameters - Reticulocyte CountBaseline, Weeks 0, 4, 24, 40

Patient's reticulocyte count will be collected at each visit. Change from Baseline will be reported at Weeks 4, 24 and 40

Energy Level (11-point Scale)Collected at Week 0, 8, 16, 24, 32, 40, 48

The patient's energy level was evaluated at each visit using an 11 point scale from 0=extremely tired to 10=extremely energetic

The Effect of Oral L-glutamine on Vital Signs - TemperatureBaseline, Weeks 4, 24, and 48

Patient's temperature will be collected at each visit. Change from Baseline will be reported at Weeks 4, 24, and 48

Effect of Oral L--glutamine on WeightBaseline, Weeks 4, 24 and 48

Weight will be measured at each visit. Change from Baseline will be reported at Weeks 4, 24, and 48

Trial Locations

Locations (5)

Kaiser Permanente

🇺🇸

Bellflower, California, United States

Harbor-UCLA Medical Center

🇺🇸

Torrance, California, United States

Jacobi Medical Center

🇺🇸

Bronx, New York, United States

Grady Memorial Hospital

🇺🇸

Atlanta, Georgia, United States

University of Medicine and Dentistry, New Jersey

🇺🇸

New Brunswick, New Jersey, United States

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