Faecal Calprotectin as a Potential Non-invasive Inflammatory Marker in Pregnancy and Inflammatory Bowel Disease

Pregnancy Clinical Trial

— PREGCAL  

Official title:

PREGCAL: Pilot Study to Assess Faecal Calprotectin as a Potential Non-invasive Inflammatory Marker in Pregnancy and Inflammatory Bowel Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02778464
• Other study ID #: 2015GAS78
• Status: Completed
• Start date: November 8, 2016
• Est. completion date: January 31, 2020

Study information

• Verified date: March 2020
• Source: The Royal Wolverhampton Hospitals NHS Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

When women with rheumatoid arthritis become pregnant 75% of them will go into remission, despite stopping medication. This phenomenon is not well understood and is not seen in other inflammatory conditions. Once they give birth they often relapse. Bacteria in the stool and inside the gut have the ability to effect the immune system and some beneficial bacteria are known to down regulate inflammatory components of the immune system. Gut bacteria are also known to alter significantly during pregnancy and in other inflammatory conditions there are low levels of beneficial bacteria associated with diseases like ulcerative colitis. There is significant crossover between rheumatoid arthritis and inflammatory bowel disease with similar arthritic symptoms and mechanisms of inflammation. There is very limited investigation of gut bacteria and rheumatoid arthritis, but some animal work has shown that treatment with probiotics and prebiotics can improve the condition. The aim of this study is to examine the bacteria in the stool of women who are pregnant with rheumatoid arthritis and identify any significant bacteria changes that might be used to direct future research.

Description:

Pregnancy has an interesting and different impact on inflammatory conditions that have much in common immunologically. In inflammatory bowel disease 33% will deteriorate, 33% will remain stable and 33% will improve. In rheumatoid arthritis 75% of women will improve. Gut microbiota alters significantly in pregnancy as do predominant immunological pathways and relapse post-partum is swift. Research on intestinal microbiota in women with inflammatory conditions is scant. The high remission rate in pregnancy gives us a unique opportunity to study the microbiota for changing patterns that could be identified in the future as potential therapeutic targets.

The study aims to identify any bacterial changes from pre-conception through pregnancy to post-partum and comparing women who relapse with rheumatoid arthritis to those who remain in remission.

Clinical condition will be assessed and stool and serum samples will be obtained from women during each trimester during pregnancy for analysis of serum and fecal biomarkers and for microbiota 16S rRNA (ribosomal ribonucleic acid) techniques. Group-specific 16S rRNA-targeted oligonucleotide probes labeled with the fluorescent dye Cy3 will be used for enumerating bacteria. The probes used will determine bifidobacteria, bacteroides, clostridia (Clostridium perfringens/histolyticum sub. Grp.), eubacterium recale-C histolyticum sub gp., agrobacterium rimae - Collinsella-Eggerthella lenta sub. Gp., Lactobacillus/Enterococcus spp., desulfovibrio spp., Faecalibacterium prausnitzii and Escherichia coli, interferon-gamma and Interleukin 10 (IL-10). Total bacteria will be enumerated using flow cytometry techniques.

The outcomes of this project would help identify microbiota patterns and bacteria species that are beneficial in rheumatoid arthritis and could be targets for potential gut immunomodulation therapy in the future to prolong periods of remissions.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 63
• Est. completion date: January 31, 2020
• Est. primary completion date: January 31, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

• Healthy pregnant women (i.e. no-IBD and no significant comorbidities). pregnant IBD and rheumatoid women with any class of disease activity, non-pregnant IBD women and Rheumatoid arthritis women aged between 18 and 40.

Exclusion Criteria:

• Coeliac disease

• Familial adenomatous polyposis and hereditary nonpolyposis

• Rheumatoid arthritis (in healthy group or IBD groups)

• Irritable bowel syndrome (ROME III criteria)

• Lactose intolerance

• Other connective tissue inflammatory diseases

• Active infection

• NSAID, aspirin or anticoagulant us,

• Recipients of antibiotics in under 4 weeks of initial trial participation

• Women on the oral contraceptive pill

Related Conditions & MeSH terms

• Colitis, Ulcerative
• Crohn Disease
• Crohn's Disease (CD)
• Inflammatory Bowel Disease (IBD)
• Inflammatory Bowel Diseases
• Intestinal Diseases
• Pregnancy
• Ulcerative Colitis (UC)

Locations

Country	Name	City	State
United Kingdom	The Royal Wolverhampton NHS Trust	Wolverhampton

Sponsors (1)

Lead Sponsor	Collaborator
The Royal Wolverhampton Hospitals NHS Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Measure faecal calprotectin in pregnant IBD patients and compare to healthy controls	Measuring faecal calprotectin in pregnant IBD patients and comparing to healthy controls in a feasibility study will see if it may be of use as a marker of intestinal inflammation during pregnancy.	24 Months
Secondary	Assess elevated f-CP in pregnant, healthy patients	If pregnant healthy patients have elevated f-CP levels outwith the standard range for normal. If they do not, then demonstrating that against an IBD cohort may mean that they can be used as surrogate markers of inflammation even in pregnancy	24 months
Secondary	Assess elevated f-CP levels in IBD patients	If the f-CP levels are raised if they compare with those of IBD patients, and therefore the marker becomes unreliable or if there is a difference, could lead to a larger national study to quantify sensitivity and specificity of the test in this group of patients	24 months
Secondary	Measure serum calprotectin levels in faeces	Measurements for serum calprotectin will also be taken to compare to faecal levels and see if they correlate to fluctuate at different times during pregnancy	24 Months
Secondary	Assess elevated f-SA12 levels in pregnant, healthy patients	If pregnant healthy patients have elevated f-SA12 levels outwith the standard range for normal. If they do not, then demonstrating that against an IBD cohort may mean that they can be used as surrogate markers of inflammation even in pregnancy	24 months
Secondary	Assess elevated f-SA12 levels in IBD patients	If the f-SA12 levels are raised if they compare with those of IBD patients, and therefore the marker becomes unreliable or if there is a difference, could lead to a larger national study to quantify sensitivity and specificity of the test in this group of patients	24 Months