Sickle Cell AnemiaPhase 2NCT00125788
L-Glutamine Therapy for Sickle Cell Anemia and Sickle ß0 Thalassemia
A Phase 2 study testing L-glutamine in people with Sickle Cell Anemia and Thalassemia, run by Emmaus Medical, Inc. at 5 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 5 years and older
- Conditions the study is for
- Sickle Cell Anemia, Thalassemia
- What is being tested?
- L-glutamine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 70 participants
- Where
- 5 sitesUnited States
- Study dates
- Mar 2004to Jul 2008
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 11Show fewer
- 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.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Grady Memorial Hospital
Atlanta, Georgia, 30303
Kaiser Permanente
Bellflower, California, 90706
University of Medicine and Dentistry, New Jersey
New Brunswick, New Jersey, 08903
Jacobi Medical Center
The Bronx, New York, 10461
Harbor-UCLA Medical Center
Torrance, California, 90502
About this study
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
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.
Read the 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.
- Conditions
- Sickle Cell Anemia, Thalassemia
- Being tested
- L-glutamine, Placebo
- Keywords
- sickle cell disease, sickle cell anemia, L-glutamine, Sickle Cell Anemia (homozygous), Sickle ß0-Thalassemia
- Medical subject headings
- Anemia, Sickle Cell, Thalassemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L-glutamineDrug
Also called oral 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.
PlaceboDrug
Also called maltodextrin
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.
| Study group | Role | What they receive |
|---|---|---|
| investigational product | Experimental | L-glutamine Receives: Drug: L-glutamine |
| placebo | Placebo comparator | maltodextrin Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Occurrences of Painful Sickle Cell Crises
The mean number of painful sickle crisis through week 48
Measured: From Week 0 through Week 48 (cumulative)
Secondary outcomes (22)
Frequency of Hospitalizations for Sickle Cell Pain
The mean number of hospitalizations through week 48
Measured: 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
Measured: 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.
Measured: 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
Measured: 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
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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.
Measured: 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
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline, Weeks 4, 24, and 48.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2005 (estimated)
- Study startMar 2004
- Primary completionJul 2008
- Study completionJul 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Sickle Cell AnemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emmaus Medical, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- FDA Office of Orphan Products Development
- Responsible party
- Sponsor
- Investigators
- Yutaka Niihara, MD, Principal investigator, CEO, Emmaus Medical, Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00125788
- Sponsor's protocol ID
- 10478
- Status last verified
- Dec 2020
- First submitted
- 1 Aug 2005
- Last updated
- 29 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Bolarinwa AB, Oduwole O, Okebe J, Ogbenna AA, Otokiti OE, Olatinwo AT. Antioxidant supplementation for sickle cell disease. Cochrane Database Syst Rev. 2024 May 22;5(5):CD013590. doi: 10.1002/14651858.CD013590.pub2.
PubMed 38775255
Study at a glance
From the registry record, last updated by the sponsor on 29 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00125788
- Acronym / sponsor ID
- 10478
- Conditions
- Sickle Cell Anemia, Thalassemia
- Keywords
- sickle cell disease, sickle cell anemia, L-glutamine, Sickle Cell Anemia (homozygous), Sickle ß0-Thalassemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- Emmaus Medical, Inc.Industry (pharma, biotech, devices)
- Collaborators
- FDA Office of Orphan Products Development
- Study start
- Mar 2004
- Primary completion
- Jul 2008 (actual)
- Study completion
- Jul 2008 (actual)
- First posted
- 2 Aug 2005 (estimated)
- Results
- Posted 29 Jan 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| investigational product | Experimental | Drug: L-glutamineL-glutamine |
| placebo | Placebo comparator | Drug: Placebomaltodextrin |
Who may qualify
- Ages
- 5 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| L-glutamineAlso: oral L-glutamineApproximately 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. | Drug | investigational product |
| PlaceboAlso: maltodextrinApproximately 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. | Drug | placebo |
Primary outcome
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
22 secondary outcomes
Frequency of Hospitalizations for Sickle Cell Pain
Time frame: From Week 0 through Week 48 (cumulative)
Frequency of Emergency Room Visits for Sickle Cell Pain
Time frame: From Week 0 through Week 48 (cumulative)
The Effect of Oral L-glutamine on Hematological Parameters - Hemoglobin
Time frame: Baseline, Weeks 4, 24 and 40
The Effect of Oral L-glutamine on Hematological Parameters - Hematocrit
Time frame: Baseline, Weeks 4, 24, and 40
The Effect of Oral L-glutamine on Hematological Parameters - Reticulocyte Count
Time frame: Baseline, Weeks 0, 4, 24, 40
Number of Participants With Narcotic Usage
Time frame: Week 24, Week 48
Energy Level (11-point Scale)
Time frame: Collected at Week 0, 8, 16, 24, 32, 40, 48
Patient Appetite (3-point Scale)
Time frame: Collected at Week 0, 8, 16, 24, 32, 40, 48
The Effect of Oral L-glutamine on Vital Signs - Blood Pressure
Time frame: Baseline, Weeks 4, 24, and 48
The Effect of Oral L-glutamine on Vital Signs - Temperature
Time frame: Baseline, Weeks 4, 24, and 48
The Effect of Oral L-glutamine on Vital Signs - Respiration
Time frame: Baseline, Weeks 4, 24, and 48
The Effect of Oral L-glutamine on Vital Signs - Pulse Rate
Time frame: Baseline, Weeks 4, 24, and 48
Effect of L-glutamine on Alcohol Use
Time frame: 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
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
The Effect of Oral L-glutamine on Subjective Quality of Life
Time frame: Baseline and Week 24 (or at time of discontinuation)
Effect of Oral L--glutamine on Height
Time frame: Baseline, Weeks 4, 24, and 48
Effect of Oral L--glutamine on Weight
Time frame: Baseline, 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.
Effect of L-glutamine on Subjective Exercise Tolerance - Minutes Patient Could Run Without Rest
Time frame: Baseline, 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.
Effect of L-glutamine on Subjective Exercise Tolerance - Distance Patient Could Run Without Rest
Time frame: Baseline, Weeks 4, 24, and 48.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38775255Bolarinwa AB, Oduwole O, Okebe J, Ogbenna AA, Otokiti OE, Olatinwo AT. Antioxidant supplementation for sickle cell disease. Cochrane Database Syst Rev. 2024 May 22;5(5):CD013590. doi: 10.1002/14651858.CD013590.pub2.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yutaka Niihara, MD principal investigator
CEO, Emmaus Medical, Inc
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing L-glutamine in people with Sickle Cell Anemia and Thalassemia, run by Emmaus Medical, Inc. at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Jan 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Occurrences of Painful Sickle Cell Crises (time frame: From Week 0 through Week 48 (cumulative)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00125788, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jan 2021.