A Phase 1/2 Study of the Safety and Preliminary Efficacy of Meldonium in Patients with Metastatic Renal Cell Carcinoma and Treatment-associated Fatigue.

Fatigue is a prevalent adverse event associated with systemic therapy using tyrosine kinase inhibitors (TKIs). Meldonium, a fatty acid oxidation inhibitor, modifies the carnitine pathway, a nutrient critical for fat metabolism. The World Anti-Doping Agency (WADA) classified meldonium as a banned substance due to its documented use by athletes aiming to enhance physical performance. In this study, the safety and preliminary efficacy of meldonium in treatment-related fatigue will be assessed.

Start Date01 Feb 2022

Sponsor / Collaborator-

CTR20140220 / SuspendedPhase 3

评估标准加米屈肼治疗慢性缺血性心力衰竭患者有效性和安全性的双盲、随机、安慰剂平行对照、多中心临床研究

[Translation] A double-blind, randomized, placebo-controlled, multicenter clinical study to evaluate the efficacy and safety of standard plus meldonium in the treatment of patients with chronic ischemic heart failure

主要目标：评估标准治疗加米屈肼相比较于标准治疗加安慰剂治疗慢性缺血性心衰病人 (NYHA II- III 级）的疗效次要目标：评估米屈肼治疗慢性缺血性心衰病人的安全性

[Translation]

Primary objective: To evaluate the efficacy of meldonium plus standard therapy compared with standard therapy plus placebo in patients with chronic ischemic heart failure (NYHA class II-III) Secondary objective: To evaluate the safety of meldonium in patients with chronic ischemic heart failure

Start Date14 Jul 2014

Sponsor / Collaborator

Jsc Grindeks

[+1]

100 Clinical Results associated with BBOX x SLC22A5

100 Translational Medicine associated with BBOX x SLC22A5

0 Patents (Medical) associated with BBOX x SLC22A5

Literatures (Medical) associated with BBOX x SLC22A5

01 Jul 2024·Cureus

Meldonium Supplementation in Professional Athletes: Career Destroyer or Lifesaver?

Review

Author: Tero-Vescan, Amelia ; Filip, Cristina ; Buț, Mădălina-Georgiana ; Pușcaș, Amalia ; Ștefănescu, Ruxandra ; Ősz, Bianca-Eugenia ; Vari, Camil-Eugen ; Istrate, Tudor-Ionuț ; Jîtcă, George

Meldonium is a substance with known anti-anginal effects demonstrated by numerous studies and human clinical trials; however, it does not possess marketing authorization within the European Union, only in ex-Soviet republics. Since 2016, meldonium has been included by the World Anti-doping Agency (WADA) on the S4 list of metabolic modulators. In performance athletes, meldonium is now considered a doping agent due to its capacity to decrease lactate production during and after exercise, its capability to enhance the storage and utilization of glycogen, and its protective action against oxidative stress. Together, these attributes can significantly improve aerobic endurance, cardiac function, and capacity as well as shorten recovery times (allowing higher intensity training), thereby enhancing performance. The purpose of this review is to highlight the most important mechanisms underlying the protective effect of meldonium against mitochondrial dysfunction (MD), which is responsible for oxidative stress, inflammation, and the cardiac changes known as "athletic heart syndrome." Meldonium acts as an inhibitor of γ-butyrobetaine hydroxylase (BBOX), preventing the de novo synthesis of carnitine and its absorption at the intestinal level via the organic cation/carnitine transporter 2 (OCTN2) and directing the oxidation of fatty acids to the peroxisomes. The decrease in mitochondrial β-oxidation of fatty acids leads to a reduction in lipid peroxidation products that cause oxidative stress and prevent the formation of acyl/acetyl-carnitines involved in numerous pathological disorders. Given the recent findings of the potentially detrimental effects of prolonged high-intensity exercise on cardiovascular health and coronary atherosclerosis, there may be legitimate arguments for the justification of the use of substances like meldonium as protective supplements for athletes.

29 May 2018·Journal of Nutrition and Metabolism

Biosynthesis of the Essential Fatty Acid Oxidation Cofactor Carnitine Is Stimulated in Heart and Liver after a Single Bout of Exercise in Mice

Article

Author: Broderick, Tom L. ; Cusimano, Frank A. ; Carlson, Chelsea ; Babu, Jeganathan Ramesh

We determined whether one single bout of exercise stimulates carnitine biosynthesis and carnitine uptake in liver and heart. Free carnitine (FC) in plasma was assayed using acetyltransferase and [14C]acetyl-CoA in Swiss Webster mice after 1 hour of moderate-intensity treadmill running or 4 hours and 8 hours into recovery. Liver and heart were removed under the same conditions for measurement of carnitine biosynthesis enzymes (liver butyrobetaine hydroxylase, γ-BBH; heart trimethyllysine dioxygenase, TMLD), organic cation transporter-2 (OCTN2, carnitine transporter), and liver peroxisome proliferator-activated receptor-alpha (PPARα, transcription factor forγ-BBH and OCTN2 synthesis). In exercised mice, FC levels in plasma decreased while heart and liver OCTN2 protein expressed increased, reflecting active uptake of FC. During recovery, the rise in FC to control levels was associated with increased liverγ-BBH expression. Protein expression of PPARαwas stimulated in liver after exercise and during recovery. Interestingly, heart TMLD protein was also detected after exercise. Acute exercise stimulates carnitine uptake in liver and heart. The rapid return of FC levels in plasma after exercise indicates carnitine biosynthesis by liver is stimulated to establish carnitine homeostasis. Our results suggest that exercise may benefit patients with carnitine deficiency syndromes.

01 Jan 2017·Kidney and Blood Pressure ResearchQ4 · MEDICINE

Acute Exercise Stimulates Carnitine Biosynthesis and OCTN2 Expression in Mouse Kidney

Q4 · MEDICINE

ArticleOA

Author: Tamura, Leslie K. ; Broderick, Tom L. ; Cusimano, Frank A. ; Carlson, Chelsea

Background/Aims: Carnitine is essential for the transport of long-chain FAs (FA) into the mitochondria for energy production. During acute exercise, the increased demand for FAs results in a state of free carnitine deficiency in plasma. The role of kidney in carnitine homeostasis after exercise is not known. Methods: Swiss Webster mice were sacrificed immediately after a 1-hour moderate intensity treadmill run, and at 4-hours and 8-hours into recovery. Non-exercising mice served as controls. Plasma was analyzed for carnitine using acetyltransferase and [14C] acetyl-CoA. Kidney was removed for gene and protein expression of butyrobetaine hydroxylase (γ-BBH), organic cation transporter (OCTN2), and peroxisome proliferator-activated receptor (PPARα), a regulator of fatty acid oxidation activated by FAs. Results: Acute exercise caused a decrease in plasma free carnitine levels. Rapid return of free carnitine to control levels during recovery was associated with increased γ-BBH expression. Both mRNA and protein levels of OCTN2 were detected in kidney after exercise and during recovery, suggesting renal transport mechanisms were stimulated. These changes were accompanied with a reciprocal increase in PPARα protein expression. Conclusions: Our results show that the decrease in free carnitine after exercise rapidly activates carnitine biosynthesis and renal transport mechanism in kidney to establish carnitine homeostasis.

Analysis

Perform a panoramic analysis of this field.

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