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

• ClinicalTrials.gov Identifier: NCT00125788
• Recruitment Status: Completed
• First Posted: August 2, 2005
• Results First Posted: January 29, 2021
• Last Update Posted: January 29, 2021
• Sponsor: Emmaus Medical, Inc.
• Collaborator: FDA Office of Orphan Products Development
• Information provided by (Responsible Party): Emmaus Medical, Inc.

Tracking Information

• First Submitted Date: August 1, 2005
• First Posted Date: August 2, 2005
• Results First Submitted Date: August 27, 2020
• Results First Posted Date: January 29, 2021
• Last Update Posted Date: January 29, 2021
• Study Start Date: March 2004
• Actual Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 11, 2021)

Number of Occurrences of Painful Sickle Cell Crises [ Time Frame: From Week 0 through Week 48 (cumulative) ]

The mean number of painful sickle crisis through week 48

• Original Primary Outcome Measures (submitted: August 1, 2005): Number of occurrences of painful sickle cell crises

Current Secondary Outcome Measures (submitted: January 11, 2021)

• Frequency of Hospitalizations for Sickle Cell Pain [ Time Frame: From Week 0 through Week 48 (cumulative) ]
  The mean number of hospitalizations through week 48
• Frequency of Emergency Room Visits for Sickle Cell Pain [ Time Frame: From Week 0 through Week 48 (cumulative) ]
  The mean number of emergency room visits through week 48
• The Effect of Oral L-glutamine on Hematological Parameters - Hemoglobin [ Time Frame: Baseline, 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 - Hematocrit [ Time Frame: Baseline, 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 Hematological Parameters - Reticulocyte Count [ Time Frame: Baseline, 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
• Number of Participants With Narcotic Usage [ Time Frame: Week 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.
• Energy Level (11-point Scale) [ Time Frame: 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
• Patient Appetite (3-point Scale) [ Time Frame: 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.
• The Effect of Oral L-glutamine on Vital Signs - Blood Pressure [ Time Frame: Baseline, 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
• The Effect of Oral L-glutamine on Vital Signs - Temperature [ Time Frame: Baseline, 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
• The Effect of Oral L-glutamine on Vital Signs - Respiration [ Time Frame: Baseline, 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 Vital Signs - Pulse Rate [ Time Frame: Baseline, 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 Use [ Time Frame: Weeks 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
• Effect of L-glutamine on Tobacco Use [ Time Frame: Weeks 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 the Number of Days Patient's Daily Activities Are Interrupted Due to Sickle Cell Pain [ Time Frame: Weeks 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
• The Effect of Oral L-glutamine on Subjective Quality of Life [ Time Frame: Baseline 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 Oral L--glutamine on Height [ Time Frame: Baseline, 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 Oral L--glutamine on Weight [ Time Frame: Baseline, Weeks 4, 24 and 48 ]
  Weight 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 Rest [ Time Frame: Baseline, 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 - Minutes Patient Could Run Without Rest [ Time Frame: Baseline, 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.
• Effect of L-glutamine on Subjective Exercise Tolerance - Distance Patient Could Walk Without Rest [ Time Frame: Baseline, 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.
• Effect of L-glutamine on Subjective Exercise Tolerance - Distance Patient Could Run Without Rest [ Time Frame: Baseline, 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.

Original Secondary Outcome Measures (submitted: August 1, 2005)

• Frequency of hospitalizations for sickle cell pain
• Frequency of emergency room visits for sickle cell pain
• Number of days patients' usual daily activities are interrupted due to sickle cell pain
• Height and weight
• Growth curve for patients less than 18 years of age
• Hematological parameters
• Narcotic usage
• Alcohol and tobacco use
• Pain level
• Energy level
• Patient activity level
• Patient appetite
• Subjective exercise tolerance
• Subjective quality of life
• L-glutaime safety assessment based on adverse events, laboratory parameters, and vital signs

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: L-Glutamine Therapy for Sickle Cell Anemia and Sickle ß0 Thalassemia
• Official Title: 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Sickle Cell Anemia
• Thalassemia

Intervention

• Drug: L-glutamine
  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.
  Other Name: oral L-glutamine
• Drug: Placebo
  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.
  Other Name: maltodextrin

Study Arms

• Experimental: investigational product
  L-glutamine
  Intervention: Drug: L-glutamine
• Placebo Comparator: placebo
  maltodextrin
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 11, 2021): 70
• Original Enrollment (submitted: August 1, 2005): 80
• Actual Study Completion Date: July 2008
• Actual Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 5 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00125788
• Other Study ID Numbers: 10478
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Emmaus Medical, Inc.
• Original Responsible Party: Not Provided
• Current Study Sponsor: Emmaus Medical, Inc.
• Original Study Sponsor: Same as current
• Collaborators: FDA Office of Orphan Products Development

Investigators

• Principal Investigator: Yutaka Niihara, MD; CEO, Emmaus Medical, Inc

• PRS Account: Emmaus Medical, Inc.
• Verification Date: December 2020