Clinical Trial Details
— Status: Withdrawn
Administrative data
| NCT number |
NCT03342287 |
| Other study ID # |
1088 |
| Secondary ID |
|
| Status |
Withdrawn |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
March 2016 |
| Est. completion date |
March 2021 |
Study information
| Verified date |
August 2021 |
| Source |
McMaster University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Irritable Bowel syndrome - constipation predominant (IBS-C) is a chronic and
disabling,disorder of the gut that is characterized by abdominal pain or discomfort.
Approximately 50% of patients with IBS-C will also meet criteria for anxiety or depression.
Anti depressant medication is widely used in the treatment of IBS. Linaclotide is a novel
medication for IBS that is also effective at relieving pain associated with IBS, which may be
in part to signalling between the gut and the brain. However, the impact of Linaclotide on
the psychiatric symptoms of anxiety and depression on IBS has not been investigated.
Description:
Irritable bowel syndrome (IBS) is a chronic, disabling functional gastrointestinal disorder
that is characterized by abdominal pain or discomfort and a disturbance in bowel habit. It
has long been recognized that psychological factors can be important in IBS, and that
bi-directional signaling between the gut and the brain is likely involved in the
pathophysiology of the syndrome. Approximately 50% of patients with IBS at a tertiary center
will also meet criteria for anxiety or depression. Anti-depressant medications are widely
used in the treatment of IBS, even without psychiatric comorbidity, with good evidence for
both tricyclic antidepressants and selective serotonin reuptake inhibitors. Unfortunately
both classes of anti-depressants have significant gastrointestinal side effects and a large
number of patients cannot tolerate the medications.
Linaclotide, a guanylate cyclase agonist, has emerged as an important, novel treatment for
patients with constipation-predominant IBS (IBS-C) and Chronic Idiopathic Constipation (CIC).
Linaclotide is effective at relieving pain associated with IBS, which may be in part mediated
by modulation of signaling between the gut and the brain. In this study the investigators
will study the effect of Linaclotide on anxiety, depression and cognitive functioning in
patients with IBS-C and CIC. If Linaclotide is also effective in treating anxiety and
depression and improving cognitive functioning in patients with IBS-C and CIC, this will be
an important therapeutic advance for the 50% of IBS patients with psychiatric comorbidity.
The investigators also propose to investigate the mechanisms by which Linaclotide may effect
psychiatric symptoms and neuropsychological functioning by measuring changes in the gut
microbiome and inflammatory biomarkers. The gut and the brain are intimately connected by
several, bidirectional, signaling pathways including neural, humoral and immune mechanisms.
The concept of the "gut-brain axis" has recently been supplanted by the "microbiota-gut-brain
axis," emphasizing the important role the gut microbiota plays in mediating brain responses.
The gut microbiota communicate with the brain through immune and neuronal pathways and some
microbiota can directly secrete neurotransmitters such as serotonin, dopamine and
gamma-aminobutyric acid (GABA) . In true bidirectional fashion, the brain can also influence
the microbiota through the secretion of cortisol and sympathetic neurotransmission, changing
gut motility, secretion and mucin production, which can affect the habitat of the resident
microbiota and thereby alter the composition of the microbiota. Alterations in gut microbiota
have been associated with irritable bowel syndrome in multiple studies.
Given the importance of the gut microbiota in mediating gut-brain responses, the
investigators propose that the gut microbiota may play a direct role in the pathophysiology
of anxiety and depression in patients with IBS. If Linaclotide is effective in reducing
psychiatric and neuropsychological symptoms in patients with IBS, this may occur through
changes in the gut microbiota, perhaps as a result of altered colonic motility and altered
habitat of resident microbiota.
