In:
Alimentary Pharmacology & Therapeutics, Wiley, Vol. 51, No. 12 ( 2020-06), p. 1332-1341
Abstract:
Linaclotide, a guanylate cyclase C agonist relieves irritable bowel syndrome with predominant constipation (IBS‐C) symptoms, but how it improves pain in humans is unknown. Aims To 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. Methods Patients 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. Results Thirty‐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). Conclusions Linaclotide 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.
Type of Medium:
Online Resource
ISSN:
0269-2813
,
1365-2036
Language:
English
Publisher:
Wiley
Publication Date:
2020
detail.hit.zdb_id:
2003094-0
SSG:
15,3
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