A Randomised, Double-blind, Placebo-controlled Trial of L-Citrulline Oral Supplementation to Improve Short and Long-term Outcomes of Admitted Febrile Paediatric Patients With Biomarker-determined High-risk of Adverse Outcomes

In low and middle-income countries, children admitted to hospital are not similarly ill, and do not all have a comparable prognosis. In fact, understanding at first encounter their risk of developing adverse outcomes (including mortality) could allow a more focused management and the tailoring of specific interventions to decrease in hospital mortality, and post discharge adverse longer-term outcomes. This clinical trial, part of the EChiLiBRiST larger project ("Development and validation of a quantitative point-of-care test for the measurement of severity biomarkers to improve risk stratification of fever syndromes and enhance child survival") has the two-fold objective of:
Assessing whether a POINT-OF-CARE rapid triaging test (PoC RTT) based on the quantitative measurement at the bedside of the "prognostic" biomarker sTREM-1 (soluble-triggering receptor expressed on myeloid cells 1) can reliably identify those admitted children with a higher risk of adverse outcomes; and
Assessing whether the therapeutic intervention (the L-arginine precursor, L-Citrulline, key in the nitric oxide biosynthesis), administered orally for 28 days to those children aged 1-<60 months identified as "moderate-to-high risk" by the prognostic biomarker can improve outcomes as compared to those receiving an indistinguishable placebo.
This second objective will be assessed in a prospective multi-country, multi-site, individually randomised, two-arm, placebo-controlled, double blind clinical trial involving
888 children 1-<60m of age admitted to hospital and determined to be at high risk of adverse outcomes by their baseline sTREM-1 levels. The trial will compare the efficacy of a twice-daily dose of L-citrulline syrup vs placebo (200-300mg/kg/day depending on weight-band; for 28 days) in reducing adverse outcomes in children with severe disease. The trial will be running independently but in parallel in two high-mortality settings in Mozambique and in Ethiopia.

Start Date01 Jan 2025

Sponsor / Collaborator

Barcelona Institute for Global Health

NCT06635902

/ RecruitingPhase 2IIT

A Phase 2 Randomized Double-blind, Placebo-controlled Clinical Trial of Intravenous Citrulline for Vaso-occlusive Pain Episode in Hospitalized Patients With Sickle Cell Disease (CONQUER SCD Pain Trial)

The goal of this clinical trial is to learn if intravenous citrulline works to treat acute pain in hospitalized patients with sickle cell disease. It will also learn about the safety of intravenous citrulline. The main questions it aims to answer are:
* Does intravenous citrulline decrease the duration of sickle cell pain during hospitalization
* What medical problems do participants have when taking intravenous citrulline? Researchers will compare intravenous citrulline to a placebo (a look-alike substance that contains no drug) to see if intravenous citrulline works to treat acute pain.
Participants will:
* Receive baseline tests and intravenous citrulline for 16 hours during the hospital stay
* After hospital discharge, visit the clinic in about 30 days for checkup and tests

Start Date22 Dec 2024

Sponsor / Collaborator

Children's National Research Institute

[+1]

NL-OMON56806

/ SuspendedNot ApplicableIIT

Boosting the bone biology. The effect of oral L-citrulline supplementation on mesenchymal stem cell concentration and osteogenic potential of BMAC in healthy humans. A randomized open-label pilot study. - Boosting the bone biology

Start Date01 Feb 2024

Sponsor / Collaborator-

100 Clinical Results associated with L-Citrulline

100 Translational Medicine associated with L-Citrulline

100 Patents (Medical) associated with L-Citrulline

11,409

Literatures (Medical) associated with L-Citrulline

24 May 2025·Journal of biomolecular structure & dynamics

Antipyretic effects of Xiangqin Jiere granules on febrile young rats revealed by combining pharmacodynamics, metabolomics, network pharmacology, molecular biology experiments and molecular docking strategies

Article

Author: Jiang, Chunrong ; Cui, Jieqiong ; Li, Huayan ; Wang, Ruirui ; He, Xiying ; Zhou, Yang ; Xu, Zhichang ; Wu, Xinchen ; Xiong, Lei

Xiangqin Jiere granules (XQJRG) is a proprietary Chinese medicine treating children's colds and fevers, but its mechanism of action is unclear. The aim of this study was to explore the antipyretic mechanisms of XQJRG based on pharmacodynamics, non-targeted metabolomics, network pharmacology, molecular biology experiments, molecular docking, and molecular dynamics (MD) simulation. Firstly, the yeast-induced fever model was constructed in young rats to study antipyretic effect of XQJRG. Metabolomics and network pharmacology studies were performed to identify the key compounds, targets and pathways involved in the antipyretic of XQJRG. Subsequently, MetScape was used to jointly analyze targets from network pharmacology and metabolites from metabolomics. Finally, the key targets were validated by enzyme-linked immunosorbent assay (ELISA), and the affinity and stability of key ingredient and targets were evaluated by molecular docking and MD simulation. The animal experimental results showed that after XQJRG treatment, body temperature of febrile rats was significantly reduced, 13 metabolites were significantly modulated, and pathways of differential metabolite enrichment were mainly related to amino acid and lipid metabolism. Network pharmacology results indicated that quercetin and kaempferol were the key active components of XQJRG, TNF, AKT1, IL6, IL1B and PTGS2 were core targets. ELISA confirmed that XQJRG significantly reduced the plasma concentrations of IL-1β, IL-6, and TNF-α, and the hypothalamic concentrations of COX-2 and PGE2. Molecular docking demonstrated that the binding energies of kaempferol to the core targets were all below -5.0 kcal/mol. MD simulation results showed that the binding free energies of TNF-kaempferol, IL6-kaempferol, IL1B-kaempferol and PTGS2-kaempferol were -87.86 kcal/mol, -70.41 kcal/mol, -69.95 kcal/mol and -106.67 kcal/mol, respectively. In conclusion, XQJRG has antipyretic effects on yeast-induced fever in young rats, and its antipyretic mechanisms may be related to the inhibition of peripheral pyrogenic cytokines release by constituents such as kaempferol, the reduction of hypothalamic fever mediator production, and the amelioration of disturbances in amino acid and lipid metabolism.

01 May 2025·BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY

L‐Arginine and L‐Citrulline for Prevention and Treatment of Pre‐Eclampsia: A Systematic Review and Meta‐Analysis

Review

Author: Hastie, Roxanne ; Cao, Jenny ; Nguyen, Phi‐Yen ; Gülmezoglu, A. Metin ; Ammerdorffer, Anne ; Vogel, Joshua P. ; Mills, Kate ; McDougall, Annie R. A. ; Makama, Maureen

ABSTRACT:

Background:

Evidence suggests L‐arginine may be effective at reducing pre‐eclampsia and related outcomes. However, whether L‐arginine can prevent or only treat pre‐eclampsia, and thus the target population and timing of initiation, remains unknown.

Objectives:

To evaluate the effects of L‐arginine and L‐citrulline (precursor of L‐arginine) on the prevention and treatment of pre‐eclampsia.

Search Strategy:

MEDLINE, Embase, CINAHL, Global Index Medicus and the Cochrane Library were searched through 7 February 2024.

Selection Criteria:

Trials administering L‐arginine or L‐citrulline to pregnant women, with the comparison group receiving placebo or standard care, were included.

Data Collection and Analysis:

Meta‐analyses were conducted separately for prevention or treatment trials, using random‐effects models.

Main Results:

Twenty randomised controlled trials (RCTs) (2028 women) and three non‐randomised trials (189 women) were included. The risk of bias was ‘high’ in eight RCTs and showed ‘some concerns’ in 12. In prevention trials, L‐arginine was associated with a reduced risk of pre‐eclampsia (relative risk [RR] 0.52; 95% confidence interval [CI], 0.35, 0.78; low‐certainty evidence, four trials) and severe pre‐eclampsia (RR 0.23; 95% CI, 0.09, 0.55; low‐certainty evidence, three trials). In treatment trials, L‐arginine may reduce mean systolic blood pressure (MD −5.64 mmHg; 95% CI, −10.66, −0.62; very low‐certainty evidence, three trials) and fetal growth restriction (RR 0.46; 95% CI, 0.26, 0.81; low‐certainty evidence, two trials). Only one study (36 women) examined L‐citrulline and reported no effect on pre‐eclampsia or blood pressure.

Conclusions:

L‐arginine may be promising for pre‐eclampsia prevention and treatment, but findings should be interpreted cautiously. More trials are needed to determine the optimal dose and time to commence supplementation and support clinical decision‐making.

01 May 2025·JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS

Quantification of amino acids in small volumes of human sweat collected from fingertips of healthy subjects at rest

Article

Author: Tsunoda, Makoto ; Kuroki, Hiroshi

Sweat is a body fluid that can be collected noninvasively. Sweat can be utilized as a biofluid for quantification of amino acids for clinical applications, such as disease screening. Amino acids are essential for many biological processes in the human body. Hence, the development of analytical methods for determining the concentrations of amino acids in human sweat can offer valuable insights into the health status of an individual. Sweat analysis can further be utilized as a tool for screening various pathological conditions. In this study, the concentrations of amino acids in small volumes of human sweat collected from fingertips of healthy subjects at rest were investigated. Reliable sweat collection was achieved by optimizing the sample collection procedure. The amino acids in human sweat were derivatized with 4-fluoro-7-nitro-2,1,3-benzoxadiazole, followed by analysis using high-performance liquid chromatography with fluorescence detection. The amino acid concentrations in sweat were quantified. The temporal variability and sex-specific differences in the concentrations of amino acids were evaluated. The results of both intra- and inter-day sweat analyses revealed that except for citrulline and arginine, the concentrations of other amino acids in sweat are relatively stable. This study proposes that the concentrations of amino acids in sweat can be determined with high accuracy, regardless of sweat collection timing. The findings of this study provide useful information that can help develop disease screening methods based on sweat analysis.

News (Medical) associated with L-Citrulline

05 Oct 2023

·www.prnewswire.com

Bizz Energy Is a Clean, Mean Way to Beat the Modern Midday Slump

The Energy Drink Formula Unleashes Unique Levels of Energy Whilst Avoiding Sugar Crashes and Unhealthy Ingredients FORT LAUDERDALE, Fla., Oct. 5, 2023 /PRNewswire/ -- The modern, remote-first work world may not have a consistent nine-to-five rhythm anymore. But that doesn't change the fact that people are still putting a lot of time into working their jobs. The Bureau of Labor Statistics reports that the average American worker clocks in at just over eight hours of labor per day (8.01, to be precise). That means, no matter when those work hours take place, they're going to extend over a significant portion of an individual's daily schedule. It also means it will involve a slump in energy and productivity at some point along the way. "Midday slumps may not always happen in the early afternoon anymore," says Gavin Jacono, founder of Bizz Energy, "But they happen at some point — and on a regular basis. If you start work at four in the morning, chances are you're going to lag after breakfast or in the late morning. If you start at noon, you'll feel tired before dinner." Northwestern Medicine points out that the biggest reason for this energy slump is that it's a predictable part of every individual's circadian cycle. However, the medical site adds that things like sleep disorders, stress, and even poor eating habits can also contribute to a slowdown in the middle of the workday. When that happens, many people turn to energy drinks as a solution — but Jacono points out that traditional energy drink formulas don't really solve the problem. "Those classic formulas use sugar, high fructose corn syrup, or aspartame. They give you a quick boost, but it's often followed by a crash — usually before your work day ends, which only means you're kicking the productivity issue down the road. And your body has to work through all of those unhealthy chemicals and additives, too. That's why we created Bizz Energy. To turn unhealthy, short-term energy drinks into healthy, long-term productivity and health solutions." Bizz Energy replaces unwanted ingredients with healthy alternatives. Each 12 oz can contains a clean shot of 200 mg of caffeine along with a punchy nutritional combination called the SuperTurk® blend. This includes an innovative soluble form of Turkesterone along with creatine, essential amino acids, L-citrulline, L-theanine, L-carnitine, niacin, and biotin. The result of this revolutionary combination is an energy drink that doubles as a nutritional supplement. It helps boost energy without a sugar crash while also stimulating metabolism and helping build muscle and strength. This makes it a clean, mean way to beat a midday slump — no matter when it might take place. About Bizz Energy Bizz Energy was founded by Gavin Jacono. The fitness and nutrition fanatic hails from New York City and is obsessed with boxing, weightlifting, and soccer. As an aspiring 17-year-old entrepreneur, Jacono launched Bizz Energy as a way to create the ultimate energy drink he had always wanted to fuel his athletic pursuits. Along with a potent dose of caffeine, the Bizz Energy formula taps into a unique form of soluble Turkesterone. It is delicious, clean, and effective. Learn more at bizzenergy.com. Media Contact: Gavin Jacono 516-637-8701 [email protected] SOURCE Bizz Energy

04 Aug 2023

·www.prnewswire.com

Bizz Energy Clears Minds and Sharpens Focus

The Clean, Zero-Sugar Energy Drink Is Good For More Than Just Physical Performance. It Boosts Brain Function, Too. FORT LAUDERDALE, Fla., Aug. 4, 2023 /PRNewswire/ -- Bizz Energy is a revolutionary new zero-sugar energy drink designed to boost performance through natural ingredients without the use of harmful chemicals or additives. While this is primarily focused on physical activities, the energy supplement's ingredients can also deliver some helpful benefits for the brain. "I designed Bizz Energy to clear my mind as well as boost my physical performance," explains company founder Gavin Jacono. "Sometimes you need to do more than run faster, lift more, or stay awake longer. Sometimes you need that sharp focus that helps you deliver at work or in school." Bizz Energy helps with cognitive function through multiple natural ingredients. For instance, creatine is a safe brain and body amino acid that has been connected to short-term memory improvement when administered orally. L-citrulline has clearly demonstrated benefits for brain function, as well. L-Theanine relieves stress disorders, improves mood, and helps with sleep. Another ingredient with the potential to help with cognition is Turkesterone. While this popular supplement is currently trending in the sports and fitness world for its physical benefits, there are also suggestions that it could aid mental health by helping cope with stress and fatigue. "Including Turkesterone was a big deal for us," says Jacono. "I knew we wanted it in there, but it's a plant-based steroid, so it isn't water-soluble. We invested in extensive research and testing and were able to develop a method to solubilize Turkesterone — it's one of the most unique things about our product." From carefully selected amino acids to soluble Turkesterone, Bizz Energy is packed with natural ingredients designed to deliver a critical dose of energy when needed. The innovative combination of natural ingredients doesn't just apply to physical performance, either. It can be a game-changer when it comes to cognitive function, too, helping to sharpen the mind and create clear focus. About Bizz Energy Bizz Energy was founded by Gavin Jacono. The fitness and nutrition fanatic hails from New York City and is obsessed with boxing, weightlifting, and soccer. As an aspiring 17-year-old entrepreneur, Jacono launched Bizz Energy as a way to create the ultimate energy drink he had always wanted to fuel his athletic pursuits. Along with a potent dose of caffeine, the Bizz Energy formula taps into a unique form of soluble Turkesterone. It is delicious, clean, and effective. Learn more at bizzenergy.com. Media Contact: Gavin Jacono 516-637-8701 [email protected] SOURCE Bizz Energy

05 Dec 2022

·www.sciencedaily.com

Not all micronutrients created equal: Study identifies some supplements that benefit cardiovascular health

Healthy diets are rich in antioxidants like amino acids, omega-3 fatty acids and vitamin C, but exactly how beneficial these micronutrients are for cardiovascular health has long been controversial. Now a new meta-analysis provides some clarity. Healthy diets are rich in antioxidants like amino acids, omega-3 fatty acids and vitamin C, but exactly how beneficial these micronutrients are for cardiovascular health has long been controversial. Now a new meta-analysis published in the Journal of the American College of Cardiology provides some clarity. Researchers systematically reviewed a total of 884 studies available to date on micronutrients taken as dietary supplements and analyzed their data. They identified several micronutrients that do reduce cardiovascular risk -- as well as others that offer no benefit or even have a negative effect. More than 883,000 patients were involved in the combined studies. "For the first time, we developed a comprehensive, evidence-based integrative map to characterize and quantify micronutrient supplements' potential effects on cardiometabolic outcomes," said Simin Liu, MD, MS, MPH, ScD, professor of epidemiology and medicine at Brown University and a principal investigator for the study. "Our study highlights the importance of micronutrient diversity and the balance of health benefits and risks." The findings could be used as the basis of future clinical trials to study specific combinations of micronutrients and their impact on cardiovascular health, he said. Antioxidant supplementation has long been thought to play a role in heart health. That's because these nutrients work to reduce oxidative stress, a known contributor to many cardiovascular diseases. Heart-healthy diets like the Mediterranean diet and the Dietary Approach to Stop Hypertension (DASH) feature foods that are naturally rich in antioxidants. However, results from studies of antioxidant supplements have been inconsistent -- one reason why this approach hasn't yet been widely adopted in preventative cardiology. "Research on micronutrient supplementation has mainly focused on the health effects of a single or a few vitamins and minerals," Liu said. "We decided to take a comprehensive and systematic approach to evaluate all the publicly available and accessible studies reporting all micronutrients, including phytochemicals and antioxidant supplements and their effects on cardiovascular risk factors as well as multiple cardiovascular diseases." The researchers looked at randomized, controlled intervention trials evaluating 27 different types of antioxidant supplements. They found strong evidence that several offered cardiovascular benefit. These included omega-3 fatty acid, which decreased mortality from cardiovascular disease; folic acid, which lowered stroke risk; and coenzyme Q10, an antioxidant sometimes marketed as CoQ10, which decreased all-cause mortality. Omega-6 fatty acid, L-arginine, L-citrulline, Vitamin D, magnesium, zinc, alpha-lipoic acid, melatonin, catechin, curcumin, flavanol, genistein and quercetin also showed evidence of reducing cardiovascular risk. Not all supplements were beneficial. Vitamin C, Vitamin D, Vitamin E and selenium showed no effect on long-term cardiovascular disease outcomes or type-2 diabetes risk. And beta carotene supplements increased all-cause mortality. According to the researchers, the findings point to the need for more personalized, precision-based dietary interventions that involve specific combinations of beneficial supplements. Further study is needed, including large, high-quality interventional trials to investigate the long-term effects of certain micronutrients on health. "Identifying the optimal mixture of micronutrients is important, as not all are beneficial, and some may even have harmful effects," Liu said.

100 Deals associated with L-Citrulline

External Link

KEGG	Wiki	ATC	Drug Bank
D07706	L-Citrulline	-	-

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Atrioventricular Septal Defect	Phase 3	United States	Asklepion Pharmaceuticals LLC	29 Jun 2022
Partial Atrioventricular Canal	Phase 3	United States	Asklepion Pharmaceuticals LLC	29 Jun 2022
Acute Lung Injury	Phase 3	United States	Asklepion Pharmaceuticals LLC	01 Aug 2016
Acute Lung Injury	Phase 3	Austria	Asklepion Pharmaceuticals LLC	01 Aug 2016
Acute Lung Injury	Phase 3	Germany	Asklepion Pharmaceuticals LLC	01 Aug 2016
Acute Lung Injury	Phase 3	Israel	Asklepion Pharmaceuticals LLC	01 Aug 2016
Heart Defects, Congenital	Phase 3	Austria	Asklepion Pharmaceuticals LLC	01 Aug 2016
Heart Defects, Congenital	Phase 3	Germany	Asklepion Pharmaceuticals LLC	01 Aug 2016
Heart Defects, Congenital	Phase 3	Israel	Asklepion Pharmaceuticals LLC	01 Aug 2016
Hypertension, Pulmonary	Phase 3	United States	Asklepion Pharmaceuticals LLC	01 May 2006

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ESC2023	Not Applicable	COVID-19 endothelin-1 \| E-selectin \| ICAM-1 ... View more	48	L-citrulline supplementation	gqjdshotjd(hcwhathalp) = ukudccvtlk kccaicfogq (gggbgdbrqw, -0.45 to -0.003)	Positive	20 May 2023
NCT04570384 (CTgov)	Phase 2	Hypoxic respiratory failure \| COVID-19 \| COVID-19 respiratory infection	65	L-Citrulline (IV L-Citrulline (Turnobi) Arm)	kaehjdqayp(xfsuaqrdwt) = xlfbneszvz ugbjfkycnh (tdrsclzxqv, 143.73) View more	-	22 Feb 2023
NCT04570384 (CTgov)	Phase 2		65	Placebo (Placebo Arm)	kaehjdqayp(xfsuaqrdwt) = jqtfstutpi ugbjfkycnh (tdrsclzxqv, 62.44) View more	-	22 Feb 2023
NCT03542812 (Pubmed \| Paediatr Drugs)	Early Phase 1	Bronchopulmonary Dysplasia \| Pulmonary Arterial Hypertension	16	L-Citrulline	njmwkavral(mdmdklucgc) = ikkecpdqaw xhzokbvivq (ltcyrpenlt ) View more	-	31 Oct 2022
NCT01120964 (CTgov)	Phase 1/2	Atrioventricular Septal Defect \| Heart Septal Defects, Atrial \| Heart Septal Defects, Ventricular	22	Intravenous L-Citrulline (Intravenous L-Citrulline)	fyjgqjmjea(kcscymovtt) = qvbedqrgoe mgxagnqfxq (fdcoxwbgas, 569.89) View more	-	21 Jun 2022
NCT01120964 (CTgov)	Phase 1/2		22	Placebo of Intravenous L-Citrulline (Placebo of Intravenous L-Citrulline)	fyjgqjmjea(kcscymovtt) = fpwbooeify mgxagnqfxq (fdcoxwbgas, 7.5) View more	-	21 Jun 2022
NCT02214290 (CTgov)	Not Applicable	Hypertension	16	Placebo	ygqpazqicj(leebvqougc) = yppcrwkxuf njduygcjrz (tshwtefbhk, 1) View more	-	29 Dec 2020
NCT01715844 (Pubmed \| JCI Insight)	Not Applicable	Asthma	41	L-citrulline 15g/day	rokhhjwoyx(wgikptrxtu) = hgzqnhruib ecpxbjyhnf (jzjgxqulum, -11 to 132) View more	-	19 Dec 2019
NCT01474863 (CTgov)	Phase 2	Acute Lung Injury \| Sepsis	72	Low Dose Citrulline (Low Dose Citrulline)	twycdvmyng(rawlmgoqyb) = yrcocrtoim qowfmfydhj (iisvotgwly, 28.8) View more	-	05 Jun 2017
NCT01474863 (CTgov)	Phase 2	Acute Lung Injury \| Sepsis	72	Placebo (Placebo)	twycdvmyng(rawlmgoqyb) = luancsahyk qowfmfydhj (iisvotgwly, 30.9) View more	-	05 Jun 2017
NCT02314689 (CTgov)	Phase 1	Anemia, Sickle Cell	4	Intravenous (IV) citrulline	kmtrceqrpo = jlqlgaubau xscogvdccd (ifmzmstyuy, umgxmdqbrv - qkszeshcrk)	-	07 Mar 2016
Pubmed \| J Nutr	Not Applicable	Fetal Growth Retardation	-	L-Citrulline	ypctcoxwdp(vxnqcszhlf) = pruazlebcq loqcyztykb (yhpstvsbhx )	-	01 Mar 2016
Pubmed \| J Nutr	Not Applicable	Fetal Growth Retardation	-	L-Citrulline	ypctcoxwdp(vxnqcszhlf) = olvmztkyqy loqcyztykb (yhpstvsbhx )	-	01 Mar 2016

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

L-Citrulline

Overview

Basic Info

Structure/Sequence

Related

External Link

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation