Protocol summary
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Study aim
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Comparison of combination therapy of L-glutamine and hydroxyurea compared with hydroxyurea alone in patients with sickle cell anemia
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Design
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The final sample size is 126 people in total (63 people in each group)
This study is a randomized, controlled, parallel clinical trial in which all patients are examined in two groups. Intervention group A will receive L-glutamine and hydroxyurea combination therapy, and group B will receive hydroxyurea treatment alone (control group).
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Settings and conduct
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This study is a randomized, controlled trial (standard treatment of hydroxyurea), double-blind and 6-month parallel group.
The allocation of two randomized block blinds is encoded in numbered envelopes and is prepared according to the sample size and will be provided to the patient's attending physician.
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Participants/Inclusion and exclusion criteria
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Patients who are at least 5 years old; diagnosed with sickle cell anemia, and have documented at least two pain crises in the past year are eligible to enter the study. Patients who receive hydroxyurea treatment at a dose that is constant for at least 3 months prior to screening and intend to continue that treatment are eligible to participate. Exclusion criteria are: Patients admitted for non-sickle cell disease within 2 months prior to screening, normalized international prothrombin time ratio greater than 2.0, serum albumin level less than 3.0 g / dL, Each blood product is taken 3 weeks before screening and has clinically significant kidney or liver disease, treated with L-glutamine within 30 days before screening.
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Intervention groups
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Receive a combination of L-glutamine and hydroxyurea
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Main outcome variables
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The main outcome variable of the study is the number of pain crises at the end of 6 months.
General information
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Reason for update
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I would like to designate the acronym "GLOBE Trial" (Glutamine and Hydroxyurea Benefit Evaluation in Sickle Cell Anemia) for this study.
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Acronym
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GLOBE Trial
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IRCT registration information
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IRCT registration number:
IRCT20210715051904N1
Registration date:
2022-02-19, 1400/11/30
Registration timing:
registered_while_recruiting
Last update:
2025-08-04, 1404/05/13
Update count:
1
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Registration date
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2022-02-19, 1400/11/30
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Registrant information
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Recruitment status
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Recruitment complete
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Funding source
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Expected recruitment start date
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2022-02-14, 1400/11/25
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Expected recruitment end date
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2022-10-17, 1401/07/25
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Actual recruitment start date
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empty
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Actual recruitment end date
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empty
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Trial completion date
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empty
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Scientific title
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Efficacy of combination therapy of L-glutamine and Hydroxyurea in comparison with Hydroxyurea alone in patients with sickle cell anemia: a randomized, double-blinded clinical trial
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Public title
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The effect of combination therapy of L-glutamine and hydroxyurea in patients with sickle cell anemia
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Purpose
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Treatment
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Inclusion/Exclusion criteria
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Inclusion criteria:
Patients with sickle-cell syndrome
Age more than five-year-old
No other accompanying hematologic diseases
All patients should be on Hydroxyurea
At least two (extreme) pain crises have been documented in the past year (defining a pain crisis as pain that results from treatment with a drug or injectable ketorolac in the emergency department (ED) (or outpatient treatment center) or during hospitalization. Becomes)
Exclusion criteria:
Occurrence of life-threatening events not related to SCD during treatment
Patient dissatisfaction with participation in the study
Serum albumin levels are less than 3 g / dL
Internationally normalized ratios of prothrombin time are higher than 2.0
The treated with L-glutamine within 30 days prior to screening.
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Age
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From 5 years old
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Gender
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Both
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Phase
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3
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Groups that have been masked
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- Participant
- Care provider
- Investigator
- Outcome assessor
- Data analyser
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Sample size
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Target sample size:
126
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Randomization (investigator's opinion)
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Randomized
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Randomization description
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This study is a randomized controlled clinical trial in which all patients are examined in two groups, which we represent with two symbols A and B. Group A will receive L-glutamine and hydroxyurea combination therapy in the intervention (intervention group) and group B will receive hydroxyurea treatment alone (control group). Participants in the study will be randomly divided into two groups A and B equal to .... individual. In order to randomly assign individuals to two equal groups to receive the intervention, the Permuted Block Randomization method with a block size of 6 has been used. The block randomization scheme was created using the free Randomization.com website (http://randomization.com). From the order of the Permuted Block Randomization table, the allocator and evaluator should not be aware of the type of intervention being performed on the individual and the size of the block. Thus, it can be said that the data allocation will remain hidden until the end of the study. Thus, each participant will be assigned to intervention or control groups and will enter the study.
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Blinding (investigator's opinion)
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Double blinded
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Blinding description
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From the order of the Permuted Block Randomizotion table, the allocator and evaluator should not be aware of the type of intervention being performed on the individual and the size of the block. Thus, it can be said that the data allocation will remain hidden until the end of the study. In this way, each participant will be assigned to intervention or control groups and will be included in the study. Pain Crisis Judgment and Laboratory Tests: All pain crises reported in the case report forms will be recorded by the researchers. An independent judging panel consisting of two hematologists-oncologists who are unaware of the assignment of the trial team will evaluate each episode to determine whether the event meets the definition of a pain crisis for performance evaluation.
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Placebo
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Used
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Assignment
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Parallel
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Other design features
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Ethics committees
1
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Ethics committee
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Approval date
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2021-09-19, 1400/06/28
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Ethics committee reference number
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IR.BPUMS.REC.1400.107
Health conditions studied
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Description of health condition studied
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Sickle cell anemia, L-glutamine, hydroxyurea, pain crisis
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ICD-10 code
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D57
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ICD-10 code description
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Sickle-cell disorders, Sickle-cell anaemia with crisis, Sickle-cell anaemia without crisis, Double heterozygous sickling disorders, Sickle-cell trait, Other sickle-cell disorders
Primary outcomes
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Description
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Number of pain crisis
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Timepoint
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Before intervention and 6 months after intervention
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Method of measurement
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Clinical examination by a pediatric hematologist and oncologist
2
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Description
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Number of hospitalizations for pain associated with sickle cell anemia
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Timepoint
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Before intervention and 6 months after intervention
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Method of measurement
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Clinical examination by a pediatric hematologist and oncologist
Secondary outcomes
1
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Description
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Number of Priapism event
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Timepoint
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Before intervention and 6 months after intervention
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Method of measurement
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Clinical examination by a pediatric hematologist and oncologist
2
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Description
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Number of acute chest syndrome
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Timepoint
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Before intervention and 6 months after intervention
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Method of measurement
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Clinical examination by a pediatric hematologist and oncologist
3
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Description
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Number of splenic sequestration events
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Timepoint
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Before intervention and 6 months after intervention
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Method of measurement
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Clinical examination by a pediatric hematologist and oncologist
Intervention groups
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Description
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Intervention group: Intervention group: The allocation of two randomized block blinds is encoded in numbered envelopes and is prepared according to the number of samples and will be provided to the patient's attending physician. Therefore, eligible patients will be randomly divided into a 1: 1 ratio for L-glutamine and hydroxyurea combination therapy or hydroxyurea alone, with randomized block allocation. The planned treatment period will be 6 months, during which patients, in addition to consuming hydroxyurea, take L-glutamine powder orally twice a day at a dose of approximately 0.3 g / kg body weight per dose (10 g, 20 g). Grams or 30 grams [maximum dose] per day). The contents of the package will be mixed with an unheated drink or food and consumed immediately. Patients will be contacted by telephone each week between monthly visits to encourage adherence. The validity of the test group assignment and the correct supply of L-glutamine or placebo for each patient will be verified by an independent research drug service. Patients can receive blood transfusions and other necessary clinical treatments if needed.
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Category
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Treatment - Drugs
2
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Description
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Control group: The allocation of two randomized block blinds is encoded in numbered envelopes and is prepared according to the number of samples and will be provided to the patient's attending physician. Therefore, eligible patients will be randomly divided into a 1: 1 ratio for L-glutamine and hydroxyurea combination therapy or hydroxyurea alone, with randomized block allocation. The planned treatment period will be 6 months, during which the control group will receive placebo powder (100% maltodextrin) orally twice a day. Experimental drug and placebo in individual packages and visually identical contain 5 grams of white powder without taste is provided, and all packages will be returned by patients to assess compliance. The contents of the package will be mixed with an unheated drink or food and consumed immediately. Patients will be contacted by telephone each week between monthly visits to encourage adherence. The validity of the test group assignment and the correct supply of L-glutamine or placebo for each patient will be verified by an independent research drug service. Patients can receive blood transfusions and other necessary clinical treatments if needed.
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Category
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Treatment - Drugs
1
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Sponsor
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Grant name
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Vice Chancellor for Research, Bushehr University of Medical Sciences
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Grant code / Reference number
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1755
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Is the source of funding the same sponsor organization/entity?
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Yes
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Title of funding source
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Boushehr University of Medical Sciences
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Proportion provided by this source
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100
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Public or private sector
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Public
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Domestic or foreign origin
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Domestic
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Category of foreign source of funding
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empty
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Country of origin
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Type of organization providing the funding
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Academic
Sharing plan
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Deidentified Individual Participant Data Set (IPD)
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Undecided - It is not yet known if there will be a plan to make this available
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Study Protocol
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Undecided - It is not yet known if there will be a plan to make this available
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Statistical Analysis Plan
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Undecided - It is not yet known if there will be a plan to make this available
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Informed Consent Form
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Undecided - It is not yet known if there will be a plan to make this available
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Clinical Study Report
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Undecided - It is not yet known if there will be a plan to make this available
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Analytic Code
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Not applicable
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Data Dictionary
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Not applicable