Trial document




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  DRKS00006051

Trial Description

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Title

Contribution of microbially synthesized vitamers to folate status and impact on inflammatory bowel diseases

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Trial Acronym

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URL of the Trial

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Brief Summary in Lay Language

Folate (Vitamin B9) is one of the key vitamins involved in normal cellular function, growth, and development.
Inflammatory bowel diseases (IBD) such as Crohn's disease (CD) are characterized by a low rate of spontaneous remission of the lesions and a constant threat of relapsing attacks. Folate deficiency occurs in 40% of IBD patients. Folate deficiency may be directly related to the extent of the mucosal damage or result from inadequate intake, increased nutritional requirements due to the inflammatory condition, intake of medication, or genetic abnormalities. Studies in healthy subjects have shown that folates produced by bacteria in the gut (=gut microbiota) could impact the folate status of the host. Our hypothesis is that folate deficiency in ileal CD subjects reflects an altered folate metabolism in the gastrointestinal tract due to a host and/or a gut microbiota component. Furthermore, we hypothesize that altered folate metabolism in the gastrointestinal tract contribute to disturbed microbiota composition and increased inflammation in ileal CD patients.
In order to answer these questions, blood and fecal samples from ileal CD patients with low and high folate status will be collected. Furthermore, dietary folate intake will be evaluated by using a dietary questionnaire.

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Brief Summary in Scientific Language

Inflammatory bowel diseases (IBD) are characterized by an undulating course of activity, with a low rate of spontaneous remission of the lesions and a constant threat of relapsing attacks. Incidence rates of IBD increased dramatically in parallel with social development but etiology of the disease is unclear. Although genetic predisposition in IBD patients has been clearly established, environmental factors are necessary contributors to IBD pathogenesis. Microbial dysbiosis is a hallmark in IBD subjects. Folate is one of the key vitamins involved in normal cellular function, growth, and development. Subclinical but biochemically relevant folate deficiency occurs in 40% of IBD patients. Folate deficiency may be directly related to the extent of the mucosal damage or result from inadequate intake, increased nutritional requirements due to the inflammatory condition, intake of medication, or genetic abnormalities. Although evidence is accumulating that bacterially derived folates could impact the folate status of the host, their production in the gut has been largely ignored. Our hypothesis is that serum folate deficiency in ileal CD subjects reflects an altered folate metabolism in the gastrointestinal tract due to a host and/or a gastrointestinal microbiota component. Furthermore, we hypothesize that altered folate metabolism in the gastrointestinal tract contribute to microbial dysbiosis and increased inflammation in ileal CD patients.
With the present project, we will use a top down-approach, to first define the quantity as well as the different forms of fecal folate vitamers obtained from ileal CD patients with different serum folate status, and to The results should lead to a greater understanding of the role of bacterially synthesized folates and will facilitate the development of strategies to alter the gut microbiota in an effort to improve folate status and to prevent or suppress host inflammation.

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Organizational Data

  •   DRKS00006051
  •   2014/04/22
  •   [---]*
  •   yes
  •   Approved
  •   EA4/109/13, Ethik-Kommission der Charité -Universitätsmedizin Berlin-
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Secondary IDs

  •   U1111-1155-2153 
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Health Condition or Problem studied

  •   K50 -  Crohn disease [regional enteritis]
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Interventions/Observational Groups

  •   Ileal Crohn's disease patients with high folate serum Status.

    The following parameters will be measured: Inflammatory and oxidative stress markers in blood (ELISA), serum folate levels, fecal folate (microbiological assay and mass spectrometry), fecal calprotectin (ELISA), variants of the MHFTR gene (qPCR), fecal microbiota composition (pyrosequencing), FOLH1 gene expression (qPCR), disease activity index, medication, dietary folate intake (food questionnaire).
  •   Ileal Crohn's disease patients with low serum folate status.

    The following parameters will be measured: Inflammatory and oxidative stress markers in blood (ELISA), serum folate levels, fecal folate (microbiological assay and mass spectrometry), fecal calprotectin (ELISA), variants of the MHFTR gene (qPCR), fecal microbiota composition (pyrosequencing), FOLH1 gene expression (qPCR), disease activity index, medication, dietary folate intake (food questionnaire).
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Characteristics

  •   Non-interventional
  •   Other
  •   Non-randomized controlled trial
  •   Open (masking not used)
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  •   Other
  •   Basic research/physiological study
  •   Parallel
  •   N/A
  •   N/A
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Primary Outcome

- Difference in the spectrum and concentration of folates in fecal samples in ileal Crohn's disease patients with low and high serum folate status

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Secondary Outcome

- Differences in inflammatory and oxidative stress markers in Crohn's disease patients with low and high serum folate status.

- Correlation between microbiota composition and inflammatory/oxidative stress markers

- Correlation between microbiota composition and gene variants relevent for folate synthesis.

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
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Recruitment

  •   Planned
  •   2014/05/01
  •   40
  •   Monocenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   60   Years
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Additional Inclusion Criteria

ileal Crohn's disease Patients

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Exclusion Criteria

1) Other Gastrointestinal Diseases
2) High consumption of alcohol (21 Portion/week)
3) High Steroid dose (>60 mg/day)
4) Blood thining medicines
5) Expecting or lactating mothers

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Addresses

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    • German Institute of Human Nutrition Potsdam Rebrücke
    • Arthur-Scheunert-Allee 114-116
    • 14558  Nuthetal
    • Germany
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    • German Institute of Human Nutrition
    • Ms.  Dr.  Delphine  Saulnier 
    • Arthur-Scheunert-Allee 114-116
    • 14558  Nuthetal
    • Germany
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    • German Institute of Human Nutrition
    • Ms.  Dr.  Delphine  Saulnier 
    • Arthur-Scheunert-Allee 114-116
    • 14558  Nuthetal
    • Germany
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Sources of Monetary or Material Support

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    • Deutsche Forschungsgemeinschaft
    • Kennedyallee 40
    • 53175  Bonn
    • Germany
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Status

  •   Recruiting planned
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Trial Publications, Results and other Documents

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* This entry means the parameter is not applicable or has not been set.