Trial reportBlood2020
Impact of arginine therapy on mitochondrial function in children with sickle cell disease during vaso-occlusive pain.
Trial report in Blood, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 23 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Arginine Therapy for the Treatment of Vaso-Occlusive Events in Children With Severe Sickle Cell Disease
Phase 2 Randomized Control Trial of Arginine Therapy for Pediatric Sickle Cell Disease Pain
Sickle Cell Disease Treatment With Arginine Therapy (STArT) Trial
Who cites it
23 citing papers in PubMed, 45 citations in OpenAlex.
- Arginine Therapy for Pain in Sickle Cell Disease: A Phase-2 Randomized, Placebo-Controlled Trial.American journal of hematology · 2025Trial
- Arginine Therapy and Cardiopulmonary Hemodynamics in Hospitalized Children with Sickle Cell Anemia: A Prospective, Double-blinded, Randomized Placebo-controlled Clinical Trial.American journal of respiratory and critical care medicine · 2022Trial
- Safety of intravenous arginine therapy in children with sickle cell disease hospitalized for vaso-occlusive pain: A randomized placebo-controlled trial in progress.American journal of hematology · 2022Trial
- Early mitophagy defects and impaired mitochondrial energy metabolism drive target organ damage progression: lessons from the Fabry heart.bioRxiv : the preprint server for biology · 2026Article
- A novel transdermal curcumin gel shows potential in improving cardiac bioenergetic functions in Berkeley sickle cell mice.Blood vessels, thrombosis & hemostasis · 2026Article
- Emergency care for children with sickle cell disease: a focus on pain and fever.Expert review of hematology · 2025Review
- Innovations in Drug Discovery for Sickle Cell Disease Targeting Oxidative Stress and NRF2 Activation-A Short Review.International journal of molecular sciences · 2025Review
- Crosstalk Between Sickle Cell Disease and Ferroptosis.International journal of molecular sciences · 2025Review
- Mitochondrial regulation of erythropoiesis in homeostasis and disease.British journal of haematology · 2024Review
- Impact of arginine therapy on kyotorphin in children with sickle cell disease and vaso-occlusive pain.Blood advances · 2024Article
- Article
- Targeting the Main Sources of Reactive Oxygen Species Production: Possible Therapeutic Implications in Chronic Pain.Current neuropharmacology · 2024Review
- Article
- Article
- Arginine Dysregulation and Myocardial Dysfunction in a Mouse Model and Children with Chronic Kidney Disease.Nutrients · 2023Article
- Effects of l-arginine supplementation in patients with sickle cell disease: A systematic review and meta-analysis of clinical trials.Health science reports · 2023Article
- Mitochondria: Emerging Consequential in Sickle Cell Disease.Journal of clinical medicine · 2023Review
- Metabolic correlates to critical speed in murine models of sickle cell disease.Frontiers in physiology · 2023Article
- Increasing nitric oxide bioavailability fails to improve collateral vessel formation in humanized sickle cell mice.Laboratory investigation; a journal of technical methods and pathology · 2022Article
- Redox Balance in β-Thalassemia and Sickle Cell Disease: A Love and Hate Relationship.Antioxidants (Basel, Switzerland) · 2022Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Altered mitochondrial function occurs in sickle cell disease (SCD), due in part to low nitric oxide (NO) bioavailability. Arginine, the substrate for NO production, becomes acutely deficient in SCD patients with vaso-occlusive pain episodes (VOE). To determine if arginine improves mitochondrial function, 12 children with SCD-VOE (13.6 ± 3 years; 67% male; 75% hemoglobin-SS) were randomized to 1 of 3 arginine doses: (1) 100 mg/kg IV 3 times/day (TID); (2) loading dose (200 mg/kg) then 100 mg/kg TID; or (3) loading dose (200 mg/kg) followed by continuous infusion (300 mg/kg per day) until discharge. Platelet-rich plasma mitochondrial activity, protein expression, and protein-carbonyls were measured from emergency department (ED) presentation vs discharge. All VOE subjects at ED presentation had significantly decreased complex-V activity compared to a steady-state cohort. Notably, complex-V activity was increased at discharge in subjects from all 3 arginine-dosing schemes; greatest increase occurred with a loading dose (P < .001). Although complex-IV and citrate synthase activities were similar in VOE platelets vs steady state, enzyme activities were significantly increased in VOE subjects after arginine-loading dose treatment. Arginine also decreased protein-carbonyl levels across all treatment doses (P < .01), suggesting a decrease in oxidative stress. Arginine therapy increases mitochondrial activity and reduces oxidative stress in children with SCD/VOE. This trial was registered at www.clinicaltrials.gov as #NCT02536170.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.