L-Glutamine Therapy Reduces Hospitalization for Sickle Cell Anemia and Sickle β°-Thalassemia Patients at Six Months – A Phase II Randomized Trial

Niihara, Yutaka; Macan, Henry; Eckman, James R.; Koh, Han; Cooper, Melanie; Ziegler, Thomas R.; Razon, Rafael; Tanaka, Kouichi R.; Stark, Charles W.; Johnson, Cage S.

doi:10.4172/2167-065x.1000116

Cited by 29 publications

(43 citation statements)

References 16 publications

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“…The mean number of painful events occurring by 24 weeks was 2.55 in the l ‐glutamine group and 5.5 in the placebo group (p=0.06) . The mean number of painful events by 48 weeks was 4.5 for the l ‐glutamine group and 10.8 for the placebo group (p=0.076).…”

Section: Resultsmentioning

confidence: 97%

“…Three studies assessing the effect of exogenous l ‐glutamine administration in patients with SCD were ultimately retained due to applicability. Study designs included one nonrandomized controlled trial and two randomized controlled trials, each published under the same first author . Table summarizes the efficacy and safety results of each study.…”

Section: Resultsmentioning

confidence: 99%

“…Other risks of bias were not identified; thus the study overall was found to have some important problems that could influence the interpretation of the results.The second and third studies were each assessed using the RoB2 tool. The second study was found to have some concerns with regard to randomization of patients . Specifically, baseline differences in years of age (30.5 years for l ‐glutamine vs 26.5 years for placebo) and sex (66.7% were female for l ‐glutamine vs 34.5% were female for placebo) were noted between treatment groups that may have had an unpredictable influence on the reporting of pain severity.…”

Section: Resultsmentioning

confidence: 99%

“…Pain secondary to VOC is the most common reason for hospital admission, with therapies aimed at the prevention of VOC a primary research focus. Three trials met inclusion criteria for this review, each published under the same first author . In the 1998 pilot study, patients treated with l ‐glutamine displayed a significant increase in NADH and the NAD redox reaction and improvements in subjective clinical outcomes when compared with baseline .…”

Section: Discussionmentioning

confidence: 99%

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Systematic Review of l‐glutamine for Prevention of Vaso‐occlusive Pain Crisis in Patients with Sickle Cell Disease

et al. 2019

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l‐glutamine was approved by the U.S. Food and Drug Administration (FDA) for sickle cell disease (SCD) in 2017. A vaso‐occlusive crisis (VOC) occurs in persons with SCD and is associated with acute pain episodes. This systematic review summarizes the evidence for l‐glutamine in the prevention of VOC and associated pain in patients with SCD. Medline, Embase, and International Pharmaceutical Abstracts were searched for records reporting on l‐glutamine use in persons with SCD. Eligibility criteria identified primary reports of investigations conducted in humans who were administered l‐glutamine, reported on outcomes related to VOC or associated pain, published in English, and were available as full text. All relevant efficacy, safety, participant demographic data, and study method characteristics were extracted and documented. Risk‐of‐bias assessments were conducted using the Risk of Bias in Non‐Randomized Studies‐of Interventions (ROBINS‐I) tool and the revised Cochrane risk‐of‐bias tool for randomized studies. Three studies assessing the effect of exogenous l‐glutamine administration in patients with SCD met eligibility criteria: one prospective nonrandomized controlled study and two prospective randomized controlled trials. Rate of VOC and related hospitalizations were reduced in patients receiving l‐glutamine, although some conflicting results were noted between studies. l‐glutamine was generally well tolerated. Limitations of one or more of the eligible studies included small sample size, nonblinding, and study groups that differed at baseline. l‐glutamine has limited high‐quality evidence supporting its use. Although l‐glutamine is FDA approved for the prevention of frequent episodes of VOC pain, only one randomized controlled trial has strong evidence to support this indication. Based on the results of a systematic review, l‐glutamine may be considered for patients unable to receive hydroxyurea or in addition to hydroxyurea for reduction in VOC and associated pain.

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Section: Resultsmentioning

confidence: 97%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Systematic Review of l‐glutamine for Prevention of Vaso‐occlusive Pain Crisis in Patients with Sickle Cell Disease

et al. 2019

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“…At 6 months of therapy, l-glutamine treatment reduced the frequency of hospitalization (nearly 40% reduction) and there was a major trend for the decrease in frequency of painful crises (over 50% reduction) favoring the l-glutamine treatment arm. 134 These results have been replicated in a larger Phase III clinical trial, but the results have not yet been published in a peer-reviewed publication, and further studies will likely be needed for regulatory approval.…”

Section: Cytoprotective Agentsmentioning

confidence: 95%

Orphan drugs for sickle vaso-occlusion: dawn of a new era of targeted treatment

Dampier¹

2015

ODRR

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Abstract:While an orphan disease in the USA, sickle cell disease (SCD), a group of genetic disorders of hemoglobin structure and function, is a major public health problem in much of the rest of the world, particularly sub-Saharan Africa. The pathophysiology of SCD stems from the formation of sickle hemoglobin polymers that deform the erythrocyte into a characteristic sickle shape, the rapidity of which is regulated by its intracellular hemoglobin concentration. Subsequent vaso-occlusion is dependent on adhesion of sickled erythrocytes, and perhaps other cellular elements, including leucocytes and platelets, to abnormal vascular endothelium using a number of receptor-ligand pairs. This propensity for vaso-occlusion may be enhanced by altered vascular tone from excessive amounts of vaso-constrictive factors or diminished amounts of vasodilatory factors. Acute pain is the hallmark symptom caused by sickle polymer formation and subsequent vaso-occlusion, and is represented in the endpoints of most previous and current clinical trial designs. Numerous failures of prior investigational agents have frustrated clinicians and patients alike. Hydroxyurea is currently the only US Food and Drug Administration-approved drug for SCD and reduces the frequency of vaso-occlusive complications in many individuals. A considerable therapeutic need remains as hydroxyurea usage is currently not approved for all types of SCD, is not always clinically effective, and requires frequent monitoring. Recent improvements in our understanding of SCD pathophysiology have generated many new therapeutic targets and associated investigational agents. For example, a number of more specific fetal hemoglobin inducers and several therapies to reduce sickle polymer formation are being tested in preclinical and early phase clinical trials. Several agents that target receptor-ligand interactions which mediate cellular adhesion to vascular endothelium have shown considerable promise and are entering Phase III trials, but present some continuing challenges in clinical trial design and conduct. Gene therapy trials are poised to start and offer the potential for curative therapy.

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Safety and efficacy of L-Glutamine in reducing the frequency of acute complications among patients with sickle cell disease: A randomized controlled study

Ebeid,

Aly,

Shaheen

et al. 2024

Ann Hematol

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To evaluate the safety and efficacy of L-glutamine in reducing vaso-occlusive crisis (VOC) and improving cerebral arterial blood flow in children with sickle cell disease (SCD). This is an interventional randomized controlled trial that recruited sixty SCD patients, aged 9.2 ± 3.7 years, who had at least two VOCs during the last 12 months and on a stable dose of hydroxyurea. They were randomly assigned in a 1:1 ratio to receive glutamine (0.3 gm/kg/dose/12h) orally for 24 weeks or the standard of care (SOC). All patients had VOCs in the last year > 3, those on glutamine had a higher number of VOCs and hospitalization for VOC in the last year. There was a decreasing trend in the number, severity, and hospitalization of VOC and a significantly lower cumulative number of VOCs and hospitalizations in the glutamine group than in SOC (p = 0.008, p < 0.001 respectively). Time-averaged mean maximum velocity for the glutamine group had a marginal increase in both middle cerebral arteries, all values remained normal within a normal range, and in both internal carotid arteries, values increased from abnormally low to normal ranges at week 24. Glutamine reduced the number of VOCs and severity and may have a potentially favorable impact on the cerebral arterial flow velocities.

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L-Glutamine Therapy Reduces Hospitalization for Sickle Cell Anemia and Sickle β°-Thalassemia Patients at Six Months – A Phase II Randomized Trial

Cited by 29 publications

References 16 publications

Systematic Review of l‐glutamine for Prevention of Vaso‐occlusive Pain Crisis in Patients with Sickle Cell Disease

Systematic Review of l‐glutamine for Prevention of Vaso‐occlusive Pain Crisis in Patients with Sickle Cell Disease

Orphan drugs for sickle vaso-occlusion: dawn of a new era of targeted treatment

Safety and efficacy of L-Glutamine in reducing the frequency of acute complications among patients with sickle cell disease: A randomized controlled study

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