Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Cognitive and Psychiatric Effects of Linaclotide on Patients With Constipation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03342287
Recruitment Status : Withdrawn
First Posted : November 14, 2017
Last Update Posted : August 31, 2021
Sponsor:
Information provided by (Responsible Party):
Paul Moayyedi, McMaster University

Tracking Information
First Submitted Date March 1, 2016
First Posted Date November 14, 2017
Last Update Posted Date August 31, 2021
Study Start Date March 2016
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: November 9, 2017)
To measure anxiety and depression using the Depression, Anxiety and Stress Scale (DASS) in patients with IBS-C and CIC before and after treatment with Linaclotide [ Time Frame: Change from baseline to week 8 ]
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: December 7, 2017)
  • To measure neuropsychological performance in Patients with IBS-C and CIC using a standardized neuropsychological assessment in patients (CNS vital signs) before and after treatment with Linaclotide [ Time Frame: Change from baseline to week 8 ]
    Neuropsychological testing will be performed using the standardized and validated CNS vital signs evaluation platform.
  • To determine changes in fecal microbiome profile before and after treatment with Linaclotide and whether these changes correlate with changes in psychiatric symptoms and cognition. [ Time Frame: Change from baseline to week 8 ]
    Fecal microbiome profile will be characterized using our in-house bioinformatics pipelines that provide measures of diversity between time points as well as differences in taxa between time points. Measurements will be aggregated to arrive at one reported value including diversity measures for microbiome analysis.
  • To determine changes in inflammatory biomarker profile before and after treatment with Linaclotide and whether these changes correlate with changes in psychiatric symptoms and cognition. [ Time Frame: Change from baseline to week 8 ]
    Inflammatory biomarkers measured will include IL-1, IL-6, TNF-alpha, IFN-gamma. Measurements will be aggregated to arrive at one reported value for average inflammatory biomarker levels.
Original Secondary Outcome Measures
 (submitted: November 9, 2017)
  • To measure neuropsychological performance in Patients with IBS-C and CIC using a standardized neuropsychological assessment in patients (CNS vital signs) before and after treatment with Linaclotide [ Time Frame: Change from baseline to week 8 ]
    Neuropsychological testing will be performed using the standardized and validated CNS vital signs evaluation platform.
  • To determine changes in fecal microbiome profile and inflammatory biomarkers before and after treatment with Linaclotide and whether these changes correlate with changes in psychiatric symptoms and cognition. [ Time Frame: Change from baseline to week 8 ]
    Fecal microbiome profile will be characterized using our in-house bioinformatics pipelines that provide measures of diversity between time points as well as differences in taxa between time points. Inflammatory biomarkers measured will include IL-1, IL-6, TNF-alpha, IFN-gamma. Psychiatric symptoms will be measured using the DASS scale and cognition using the CNS vital signs platform. Outcome measures will be aggregated to arrive at one reported value including diversity measures for microbiome analysis, average inflammatory biomarker levels.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Cognitive and Psychiatric Effects of Linaclotide on Patients With Constipation
Official Title Cognitive and Psychiatric Effects of Linaclotide on Patients With Irritable Bowel Syndrome-Constipation Predominant and Chronic Idiopathic Constipation
Brief 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.

Detailed 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.

Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
Blood samples and fecal samples collected.
Sampling Method Probability Sample
Study Population Patients with IBS-C or CIC starting on Linaclotide
Condition
  • Constipation
  • Irritable Bowel Syndrome
Intervention
  • Other: questionnaires
    Questionnaires rating IBS symptoms, constipation, anxiety and depression
  • Other: cognitive evaluation
    Administration of online cognitive battery
  • Other: Blood
    Measurement of cytokines/inflammatory biomarkers
  • Other: Fecal sample
    Measurement of the gut microbiome
Study Groups/Cohorts Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Withdrawn
Actual Enrollment
 (submitted: August 30, 2021)
0
Original Estimated Enrollment
 (submitted: November 9, 2017)
100
Estimated Study Completion Date March 2021
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • IBS-C or CIC as defined by Rome III criteria
  • able to provide and sign informed consent
  • age 18-65 years

Exclusion Criteria:

  • Previous diagnosis of bipolar, schizophrenia, or schizoaffective disorder
  • psychosis
  • active suicidal thoughts
  • presence of a major neurocognitive disorder, delirium or other cognitive disorder
  • active substance dependence ( including the use of cannabis more than 3 times per week
  • active eating disorder
  • pregnant or breastfeeding
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries Canada
Removed Location Countries  
 
Administrative Information
NCT Number NCT03342287
Other Study ID Numbers 1088
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party Paul Moayyedi, McMaster University
Study Sponsor McMaster University
Collaborators Not Provided
Investigators
Principal Investigator: Paul Moayyedi, MD, PhD McMaster University
PRS Account McMaster University
Verification Date August 2021