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

Completed
Conditions
Ulcerative Colitis (UC)
Inflammatory Bowel Disease (IBD)
Pregnancy
Crohn's Disease (CD)
Registration Number
NCT02778464
Lead Sponsor
The Royal Wolverhampton Hospitals NHS Trust
Brief 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.

Detailed 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 & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
63
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

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Measure faecal calprotectin in pregnant IBD patients and compare to healthy controls24 Months

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.

Secondary Outcome Measures
NameTimeMethod
Assess elevated f-CP levels in IBD patients24 months

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

Assess elevated f-SA12 levels in pregnant, healthy patients24 months

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

Assess elevated f-CP in pregnant, healthy patients24 months

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

Measure serum calprotectin levels in faeces24 Months

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

Assess elevated f-SA12 levels in IBD patients24 Months

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

Trial Locations

Locations (1)

The Royal Wolverhampton NHS Trust

🇬🇧

Wolverhampton, United Kingdom

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