L-threonic acid magnesium salt (NRCT-101) / Neurocentria - LARVOL DELTA

Magnesium-L-Threonate Attenuates Bladder Overactivity in Cyclophosphamide-Induced Cystitis through TNF-α/NF-KB Signaling Inhibition and Restoration of the Bladder Tight Junction Integrity (AUA 2025) - "Source of Funding: This study was funded by grants from the National Natural Science Foundation of China (No. Oral administration of L-TAMS reduced bladder overactivity in CYP-induced cystitis rats by inhibiting TNF-α/NF-κB signaling pathway and restoring the integrity of the bladder tight junction barrier. Our findings suggest that L-TAMS may offer therapeutic benefits for managing lower urinary tract symptoms in patients with BPS/IC."

Interstitial Cystitis • Musculoskeletal Pain • Oncology • Pain • IL1B • OCLN • TJP1 • TNFA • UPK3

A Phase 2 Randomized Double-Blind, Parallel, Adaptive-Design, Clinical Trial to Evaluate the Safety and Efficacy of NRCT-101SR with NRCT-202XR Compared to NRCT-202XR Alone in Subjects with Attention-Deficit/Hyperactivity Disorder (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Neurocentria, Inc. | Initiation date: Nov 2024 ➔ Feb 2025

Trial initiation date • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

Study to Evaluate NRCT-101SR in Pediatric Subjects with ADHD (clinicaltrials.gov) - P2/3 | N=160 | Recruiting | Sponsor: Neurocentria, Inc. | Trial completion date: Feb 2025 ➔ Feb 2026 | Trial primary completion date: Dec 2024 ➔ Dec 2025

Trial completion date • Trial primary completion date • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Pediatrics • Psychiatry

A Phase 2 Randomized Double-Blind, Parallel, Adaptive-Design, Clinical Trial to Evaluate the Safety and Efficacy of NRCT-101SR with NRCT-202XR Compared to NRCT-202XR Alone in Subjects with Attention-Deficit/Hyperactivity Disorder (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Neurocentria, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

A Phase 2 Randomized Double-Blind, Parallel, Adaptive-Design, Clinical Trial to Evaluate the Safety and Efficacy of NRCT-101SR with NRCT-202XR Compared to NRCT-202XR Alone in Subjects with Attention-Deficit/Hyperactivity Disorder (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: Neurocentria, Inc.

New P2 trial • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

Recent advances in pharmacological management of attention-deficit/hyperactivity disorder: moving beyond stimulants. (PubMed, Expert Opin Pharmacother) - "Stimulants, such as amphetamine and methylphenidate, are available in more than two dozen formulations, but all have similar adverse effects and carry a risk of misuse and dependence...Two, including atomoxetine and viloxazine extended-release (ER), are approved by the Food and Drug Administration for the treatment of ADHD in children and adults. Two others, clonidine ER and guanfacine ER, are only approved for children and adolescents in the U.S. Several other compounds are under investigation. Drugs in Phase 3 trials include centanafadine, solriamfetol, and L-threonic acid magnesium salt...Lack of individual drug response and tolerability are reasons many stop treatment. Development of new nonstimulants may offer hope for patients who need medication alternatives."

Journal • Review • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • Behavior Disorders • CNS Disorders • Mental Retardation • Psychiatry

Oral application of magnesium-L-threonate alleviates radicular pain by inhibiting neuro-inflammation dependent central sensitization of rats. (PubMed, Brain Res) - "Oral application of L-TAMS alleviates radicular pain by inhibiting neuro-inflammation dependent central sensitization of rats."

Journal • Preclinical • Immunology • Inflammation • Musculoskeletal Diseases • Oncology • Pain • IL1B • IL6 • TNFA

Study to Evaluate NRCT-101SR in Adult Attention Deficit Hyperactivity Disorder (ADHD) (clinicaltrials.gov) - P2/3 | N=223 | Completed | Sponsor: Neurocentria, Inc. | Active, not recruiting ➔ Completed

Trial completion • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

Study to Evaluate NRCT-101SR in Pediatric Subjects With ADHD (clinicaltrials.gov) - P2/3 | N=160 | Recruiting | Sponsor: Neurocentria, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Pediatrics • Psychiatry

Riboflavin-LSD1 axis participates in the in vivo tumor-associated macrophage morphology in human colorectal liver metastases. (PubMed, Cancer Immunol Immunother) - "In colorectal liver metastasis (CLM), TAM morphology correlates with prognosis, with smaller TAMs (S-TAMs) conferring a more favorable prognosis than larger TAMs (L-TAMs)...The inflammatory stimuli promoted by TNFα induced the increased expression of riboflavin transporter SLC52A3 and LSD1 in M2 macrophages. The modulation of the riboflavin-LSD1 axis represents a potential target for reprogramming TAM subtypes, paving the way for promising anti-tumor therapeutic strategies."

Journal • Preclinical • Oncology • KDM1A • SLC2A3 • TNFA

Study to Evaluate NRCT-101SR in Pediatric Subjects With ADHD (clinicaltrials.gov) - P2/3 | N=160 | Not yet recruiting | Sponsor: Neurocentria, Inc.

New P2/3 trial • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Pediatrics • Psychiatry

Study to Evaluate NRCT-101SR in Adult Attention Deficit Hyperactivity Disorder (ADHD) (clinicaltrials.gov) - P2/3 | N=223 | Active, not recruiting | Sponsor: Neurocentria, Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2023 ➔ Feb 2024 | Trial primary completion date: Oct 2023 ➔ Feb 2024

Enrollment closed • Trial completion date • Trial primary completion date • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

What’s New With Medication Treatment for ADHD? (AACAP 2023) - "The furthest along for ADHD is centanafadine, a dopamine, norepinephrine, and serotonin reuptake inhibitor. Others in clinical trials include: dexmethylphenidate ER (CTX 1301), a stimulant designed to last up to 16 hours; L-threonic acid magnesium salt, a compound that has been shown to improve ADHD symptoms in adults; and solriamfetol, a dopamine and norepinephrine reuptake inhibitor that is FDA-approved for patients with narcolepsy. Conclusions Participants will gain a better understanding of the efficacy and safety of newly approved FDA products, as well as investigational products, for the treatment of ADHD."

ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Narcolepsy • Psychiatry • Sleep Disorder

Role of magnesium-L-Threonate in alleviating skin/muscle incision and retraction induced mechanical allodynia and anxiodepressive-like behaviors in male rats. (PubMed, Brain Res) - "Together, our study demonstrates the contributing role of magnesium deficiency in the pathology of surgery-induced chronic pain and negative emotion. Moreover, we suggest that L-TAMS might be a novel approach to treat CPSP and its emotional comorbidities."

Journal • Preclinical • CNS Disorders • Pain • IL1B • IL6 • TNFA

Macrophage morphology and distribution are strong predictors of prognosis in resected colorectal liver metastases: results from an external retrospective observational study. (PubMed, Int J Surg) - "This external validation confirms that morphometric characterization of TAMs can serve as a simple readout of their diversity and allows to reliably stratify patient outcomes and predict disease recurrence after hepatectomy for CLMs."

Journal • Observational data • Retrospective data • Oncology

Macrophage Morphology Is a Strong Predictor of Prognosis in Colorectal Liver Metastases: Results from an External Validation (IHPBA 2022) - "This external validation study has demonstrated that morphological characteristics of TAMs can be used to reliably stratify patient outcomes and predict recurrence. Future perspectives could include development of an AI-based software to accurately analyze TAMs and development of an internationally validated immunoscore for CLMs. Future treatment strategies could aim to target specific complement components, scavenger and phagocytic receptors, and lipid metabolism to preferentially impact L-TAMs, translating them from a strong prognostic indicator to a therapeutic target.  >"

Metabolic Disorders • Oncology • CD163

INNATE IMMUNITY IN COLORECTAL LIVER METASTASES: MACROPHAGE MORPHOLOGY AND DISTRIBUTION ARE STRONG PREDICTORS OF PROGNOSIS. AN EXTERNAL VALIDATION. (DDW 2022) - "Future perspectives could include involve an AI-based tool to accurately analyze TAMs and the development of an internationally validated immunoscore for CLMs. In fact, future treatment strategies could aim to target specific complement components, scavenger and phagocytic receptors, and lipid metabolism to preferentially impact L-TAMs, translating them from a strong prognostic indicator to a therapeutic target."

Metabolic Disorders • Oncology • CD163

INNATE IMMUNITY IN COLORECTAL LIVER METASTASES: MACROPHAGE MORPHOLOGY AND DISTRIBUTION ARE STRONG PREDICTORS OF PROGNOSIS. AN EXTERNAL VALIDATION. (SSAT 2022) - "This external validation study confirms that morphometric characterization of TAMs can serve as a simple readout of their diversity and allows to reliably stratify patient outcomes and predict recurrence. Future perspectives could include involve an AI-based tool to accurately analyze TAMs and the development of an internationally validated immunoscore for CLMs. In fact, future treatment strategies could aim to target specific complement components, scavenger and phagocytic receptors, and lipid metabolism to preferentially impact L-TAMs, translating them from a strong prognostic indicator to a therapeutic target.A."

Metabolic Disorders • Oncology • CD163

Oral application of magnesium-L-threonate enhances analgesia and reduces the dosage of opioids needed in advanced cancer patients-A randomized, double-blind, placebo-controlled trial. (PubMed, Cancer Med) - "L-TAMS outperforms a placebo in enhancing the analgesic effect of opioids and reducing the necessary opioid dosage. Moreover, L-TAMS can significantly relieve opioid-induced constipation. These advantages may be beneficial to patients with advanced cancer."

Clinical • Journal • Metastases • Constipation • Gastroenterology • Gastrointestinal Disorder • Oncology • Pain

Study to Evaluate NRCT-101SR in Adult Attention Deficit Hyperactivity Disorder (ADHD) (clinicaltrials.gov) - P2/3 | N=216 | Recruiting | Sponsor: Neurocentria, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

Study to Evaluate NRCT-101SR in Adult Attention Deficit Hyperactivity Disorder (ADHD) (clinicaltrials.gov) - P2/3 | N=216 | Not yet recruiting | Sponsor: Neurocentria, Inc.

New P2/3 trial • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

L-Threonic Acid Magnesium Salt Supplementation in ADHD: An Open-Label Pilot Study. (PubMed, J Diet Suppl) - P2; "Subjects received up to 12 weeks of open-label LTAMS administered as MMFS302 and MMFS202...Nearly half of participants met our definition of ADHD symptom clinical response. These results support the need to further evaluate this compound in larger samples under double-blind conditions."

Clinical • Journal