Trial reportGastroenterology2011
The tryptophan hydroxylase inhibitor LX1031 shows clinical benefit in patients with nonconstipating irritable bowel syndrome.
Trial report in Gastroenterology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
What it found
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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.
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Who cites it
52 citing papers in PubMed, 101 citations in OpenAlex.
- Effect of Shugan Jianpi Recipe Combined with Cross Moxibustion on Biochemical Examination Indexes and Total Score of TCM Symptoms in Patients with Spleen-Stomach Damp-Heat Diarrhea Irritable Bowel Syndrome.Computational and mathematical methods in medicine · 2022Trial
- Abnormalities of mucosal serotonin metabolism and 5-HTAlimentary pharmacology & therapeutics · 2019Trial
- A randomised trial of ondansetron for the treatment of irritable bowel syndrome with diarrhoea.Gut · 2014Trial
- Review
- Efficient Synthesis of Chiral Aryl Alcohol with a Novel Kosakonia radicincitans Isolate in Tween 20/L-carnitine: Lysine-Containing Synergistic Reaction System.Applied biochemistry and biotechnology · 2024Article
- Early-Life Stress Induced by Neonatal Maternal Separation Leads to Intestinal 5-HT Accumulation and Causes Intestinal Dysfunction.Journal of inflammation research · 2024Article
- Serotonergic Control of Gastrointestinal Development, Motility, and Inflammation.Comprehensive Physiology · 2023Article
- 5-HTLaboratory investigation; a journal of technical methods and pathology · 2022Article
- Role of Ion Channels in the Chemotransduction and Mechanotransduction in Digestive Function and Feeding Behavior.International journal of molecular sciences · 2022Review
- Herpes Simplex Virus-1 Induced Serotonin-Associated Metabolic Pathways Correlate With Severity of Virus- and Inflammation-Associated Ocular Disease.Frontiers in microbiology · 2022Article
- Unraveling Autocrine Signaling Pathways through Metabolic Fingerprinting in Serous Ovarian Cancer Cells.Biomedicines · 2021Article
- Tryptophan-derived serotonin-kynurenine balance in immune activation and intestinal inflammation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Review
- Inflammation and Overlap of Irritable Bowel Syndrome and Functional Dyspepsia.Journal of neurogastroenterology and motility · 2021Review
- Serotonin in the Pathogenesis of Lymphocytic Colitis.Journal of clinical medicine · 2021Article
- International Union of Basic and Clinical Pharmacology. CX. Classification of Receptors for 5-hydroxytryptamine; Pharmacology and Function.Pharmacological reviews · 2021Review
- Amino Acid Trp: The Far Out Impacts of Host and Commensal Tryptophan Metabolism.Frontiers in immunology · 2021Review
- Predicting human disease mutations and identifying drug targets from mouse gene knockout phenotyping campaigns.Disease models & mechanisms · 2019Review
- Impacts of Psychological Stress on Osteoporosis: Clinical Implications and Treatment Interactions.Frontiers in psychiatry · 2019Review
- New treatments and therapeutic targets for IBS and other functional bowel disorders.Nature reviews. Gastroenterology & hepatology · 2018Review
- The TPH1 rs211105 gene polymorphism affects abdominal symptoms and quality of life of diarrhea-predominant irritable bowel syndrome.Journal of clinical biochemistry and nutrition · 2018Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsSerotonin (5-hydroxytryptamine [5-HT]) has an important role in gastrointestinal function. LX1031 is an oral, locally acting, small molecule inhibitor of tryptophan hydroxylase (TPH). Local inhibition of TPH in the gastrointestinal tract might reduce mucosal production of serotonin (5-HT) and be used to treat patients with nonconstipating irritable bowel syndrome (IBS).
methodsWe evaluated 2 dose levels of LX1031 (250 mg or 1000 mg, given 4 times/day) in a 28-day, multicenter, randomized, double-blind, placebo-controlled study of 155 patients with nonconstipating IBS. 5-hydroxyindoleacetic acid (5-HIAA), a biomarker of pharmacodynamic activity, was measured in urine samples at baseline (24 hours after LX1031 administration), and at weeks 4 and 6 (n = 76).
resultsEach dose of LX1031 was safe and well-tolerated. The primary efficacy end point, relief of IBS pain and discomfort, improved significantly in patients given 1000 mg LX1031 (25.5%), compared with those given placebo, at week 1 (P = .018); with nonsignificant improvements at weeks 2, 3, and 4 (17.9%, 16.3%, and 11.6%, respectively). Symptom improvement correlated with a dose-dependent reduction in 5-HIAA, a marker for TPH inhibition, from baseline until week 4. This suggests the efficacy of LX1031 is related to the extent of inhibition of 5-HT biosynthesis. Stool consistency significantly improved, compared with the group given placebo, at weeks 1 and 4 (P < .01) and at week 2 (P < .001).
conclusionsIn a phase 2 study, LX1031 was well tolerated, relieving symptoms and increasing stool consistency in patients with nonconstipating IBS. Symptom relief was associated with reduced levels of 5-HIAA in urine samples. This marker might be used to identify patients with nonconstipating IBS who respond to inhibitors of 5-HT synthesis.
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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.