Trial reportAlimentary pharmacology & therapeutics2020
Randomised clinical trial: linaclotide vs placebo-a study of bi-directional gut and brain axis.
Trial report in Alimentary pharmacology & therapeutics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02078323 (Investigation of Linaclotide's Effect on the Bi-directional Brain and Gut Axis in IBS-C Patients), which is not on this map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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.
Investigation of Linaclotide's Effect on the Bi-directional Brain and Gut Axis in IBS-C Patients
Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- Guideline
- Plecanatide Improves Abdominal Bloating and Bowel Symptoms of Irritable Bowel Syndrome with Constipation.Digestive diseases and sciences · 2024Trial
- Effects of Translumbosacral Neuromodulation Therapy on Gut and Brain Interactions and Anorectal Neuropathy in Fecal Incontinence: A Randomized Study.Neuromodulation : journal of the International Neuromodulation Society · 2021Trial
- Sensory Adaptation Training or Escitalopram for IBS With Constipation and Rectal Hypersensitivity: A Randomized Controlled Trial.Clinical and translational gastroenterology · 2021Trial
- Randomised clinical trial: linaclotide vs placebo-a study of bi-directional gut and brain axis.Alimentary pharmacology & therapeutics · 2020Trial
- Irritable Bowel Syndrome with Constipation: Diagnosis and Multisymptom Management Beyond Abdominal Pain and Bowel Movement Frequency: A Review.Advances in therapy · 2026Review
- The gut microbiota participates in the effect of linaclotide in patients with irritable bowel syndrome with constipation (IBS-C): a multicenter, prospective, pre-post study.Journal of translational medicine · 2024Article
- Gut liver brain axis in diseases: the implications for therapeutic interventions.Signal transduction and targeted therapy · 2023Review
- Parkinson's Disease and Diabetes Mellitus: Synergistic Effects on Pathophysiology and GI Motility.Current gastroenterology reports · 2023Review
- Guanylate cyclase-C agonists as peripherally acting treatments of chronic visceral pain.Trends in pharmacological sciences · 2022Review
- Efficacy ofFrontiers in nutrition · 2022Article
- Receptor Guanylyl Cyclase C and Cyclic GMP in Health and Disease: Perspectives and Therapeutic Opportunities.Frontiers in endocrinology · 2022Review
- The critical role of gut microbiota in obesity.Frontiers in endocrinology · 2022Review
- Review
- Review article: diagnosis, management and patient perspectives of the spectrum of constipation disorders.Alimentary pharmacology & therapeutics · 2021Review
- Diagnosing Constipation Spectrum Disorders in a Primary Care Setting.Journal of clinical medicine · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLinaclotide, a guanylate cyclase C agonist relieves irritable bowel syndrome with predominant constipation (IBS-C) symptoms, but how it improves pain in humans is unknown.
aimsTo investigate the effects of linaclotide and placebo on the afferent and efferent gut-brain-gut signalling in IBS-C patients, in a randomised clinical trial.
methodsPatients with IBS-C (Rome III) and rectal hypersensitivity were randomised (2:1) to receive linaclotide (290 µg) or placebo for 10 weeks and undergo bi-directional gut and brain axis assessment using anorectal electrical stimulations and transcranial/transspinal-anorectal magnetic stimulations. Rectal sensations were examined by balloon distention. Assessments included abdominal pain, bowel symptoms and quality of life (QOL) scores. Primary outcomes were latencies of recto-cortical and cortico-rectal evoked potentials.
resultsThirty-nine patients participated; 26 received linaclotide and 13 received placebo. Rectal cortical evoked potentials latencies (milliseconds) were significantly prolonged with linaclotide compared to baseline (P1:Δ 19 ± 6, P < 0.005; N1:Δ 20 ± 7, P < 0.02) but not with placebo (P1:Δ 3 ± 5; N1:Δ 4.7 ± 5,P = 0.3) or between groups. The efferent cortico-anorectal and spino-anorectal latencies were unchanged. The maximum tolerable rectal volume (cc) increased significantly with linaclotide compared to baseline (P < 0.001) and placebo (Δ 29 ± 10 vs 4 ± 20, (P < 0.03). Abdominal pain decreased (P < 0.001) with linaclotide but not between groups. Complete spontaneous bowel movement frequency increased (P < 0.001), and IBS-QOL scores improved (P = 0.01) with linaclotide compared to baseline and placebo. There was no difference in overall responders between linaclotide and placebo (54% vs 23%, P = 0.13).
conclusionsLinaclotide prolongs afferent gut-brain signalling from baseline but both afferent and efferent signalling were unaffected compared to placebo. Linaclotide significantly improves rectal hypersensitivity, IBS-C symptoms and QOL compared to placebo. These mechanisms may explain the effects of linaclotide on pain relief in IBS-C patients. ClinicalTrials.Gov: Registered at Clinical trials.gov no NCT02078323.
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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.