Trial document




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  DRKS00015784

Trial Description

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Title

Metabolic health and immune status in young obese subjects

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Trial Acronym

MeGA

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URL of the Trial

https://www.unika-t.de/studienzentrum/studienzentrum-epidemiologie/mega/

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Brief Summary in Lay Language

Obesity is a major public health problem worldwide with severe medical and economic consequences. In Germany, approximately one quarter of adult men and women is obese. Obesity and associated insulin resistance predispose individuals to develop chronic metabolic diseases, such as type 2 diabetes, and cardiovascular disease. Adipose tissue lies at the crossroad of nutrition, metabolism and immunity and adipose tissue inflammation was proposed as a central mechanism connecting obesity with its metabolic and vascular complications. Evidence suggests that vascular and metabolic dysfunctions are closely regulated by coincident immune regulation. In addition, recent clinical investigations have demonstrated a clear relationship between the gut microbiota and the immune system. Due to still lacking information about the interactive effects of the above factors on disease pathogenesis and progression in humans, a study with obese adults (BMI >30 kg/m²) aged 25-65 years (50% men, 50% women), who plan to have an influenza vaccination with their treating physician in autumn will be established. A group of normal-weight healthy subjects (BMI: 20-24.99 kg/m2) will be recruited as reference group. Participants will undertake extensive examinations including body composition analysis, measurements of metabolic characteristics and imaging data, determination of health-related behaviours, and collection of biomaterials (blood, urine, stool samples) to measure immunometabolic profiles. All participants should attend four visits over a 21 months period.
The study will contribute to a deeper insight into the differences between healthy normal- weight and obese persons regarding metabolic health, immune status, and gut microbiota.
It will be investigated, whether and to what extent the innate and adaptive immune system differs between obese and normal-weight persons before and after an immune system challenge and how metabolic parameters and gut microbiome as well as gut metabolites are associated with inflammatory and immune markers.

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Brief Summary in Scientific Language

Obesity and associated insulin resistance predispose individuals to develop chronic metabolic diseases, such as type 2 diabetes, and cardiovascular disease. Furthermore, it is now known that there is a link between obesity and diseases that are less obviously linked to metabolic derangements, including several forms of cancer, Alzheimer’s disease and asthma. Environmental, dietary, lifestyle and genetic factors have been identified to describe the pathophysiology of obesity; however, the biological basis linking obesity to metabolic dysfunction and the subsequent development of chronic diseases has not been fully elucidated so far.
During the past decade, it became clear that inflammation is a key feature of obesity and chronic diseases. Inflammation as short-term adaptive response to injuries is a crucial component of tissue repair and involves integration of many complex signals in distinct cells and organs. However, the long-term consequences of prolonged inflammation are often not beneficial. This seems to be the case in metabolic diseases triggered by nutrients and metabolic surplus (metabolically triggered inflammation). Accumulating evidence points to localized inflammation in adipose tissue, which in turn promotes systemic inflammation, characterized by abnormal cytokine production, increased acute-phase reactants and other mediators, and activation of a network of inflammatory signalling pathways. The finding that tumour necrosis factor-alpha (TNF-alpha), a pro-inflammatory cytokine that activates various signal transduction cascades, is overexpressed in the adipose tissue of obese mice provided the first clear link between obesity, diabetes and chronic inflammation.
Recent studies confirmed the unusual properties of adipocytes and centrally placed adipose tissue as a crucial site in the generation of inflammatory response and mediators. Adipose tissue serves as a key site for the interaction of adipocytes with other effectors of the immune system and there are striking commonalities between adipocytes and a diverse set of immune cells (including T cells, macrophages and dendritic cells). These features range from complement activation and production of inflammatory mediators to pathogen sensing and phagocytic properties. Thus, a possibility to explore the link between metabolism and inflammation might be to investigate the functional interface of cells of primarily immune or metabolic nature, such as adipocytes and macrophages, and the shared response systems. So far, the understanding of interactions between immune and metabolic cells is incomplete.
Much of the previous research linking inflammation and metabolic diseases - called immunometabolism - has focused on the role of the innate immune response mainly investigating the importance of macrophages in this context. However, recent studies also point to an important role for the adaptive immune system. T and B lymphocytes rely on antigen recognition and account for diverse populations of immune cells with either primarily pro-inflammatory or regulatory functions. Thus, newer studies in the field identified components of both the innate and adaptive immune response as key players in regulating inflammatory processes.

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Organizational Data

  •   DRKS00015784
  •   2018/11/23
  •   [---]*
  •   yes
  •   Approved
  •   18-637, Ethik-Kommission der Medizinischen Fakultät der Ludwig-Maximilians-Universität München
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Secondary IDs

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Health Condition or Problem studied

  •   E66 -  Obesity
  •   E11 -  Type 2 diabetes mellitus
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Interventions/Observational Groups

  •   Adult, overweight (Body mass index > 30 kg/m²) with influenca vaccination
  •   Healthy adult normal weight individuals (BMI: 20-24.99 kg/m²) with influenca vaccination
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Characteristics

  •   Non-interventional
  •   Epidemiological study
  •   Non-randomized controlled trial
  •   Open (masking not used)
  •   [---]*
  •   Other
  •   Prevention
  •   Parallel
  •   N/A
  •   N/A
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Primary Outcome

B-lymphocytes (FACS)

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Secondary Outcome

Oral glucose tolerance test.
Immunophenotyping of T-cell subpopulations (CD4+, CD8+, NK cells, Tregs, memory T cells),
Inflammation markers: Plasma levels of interleukins, IFN-gamma, CCL5, TNF-alpha

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • other 
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Recruitment

  •   Actual
  •   2018/11/20
  •   400
  •   Monocenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   25   Years
  •   65   Years
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Additional Inclusion Criteria

Age: 25-65 years
Exposure: Normal weight (BMI: 20-24.99 kg/m²) and overweight/adipose (BMI: >30kg/m²)

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Exclusion Criteria

- Antibiotics or corticosteroids use 3 months prior to the baseline visit
- Current use of immunosuppressive medicine
- History of significant illness
- Acute febrile illness

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Addresses

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    • Lehrstuhl für Epidemiologieder LMU München am UNIKA-T Augsburg
    • Ms.  Professorin Dr med.  Christine  Meisinger 
    • Neusässer Str. 47
    • 86156  Augsburg
    • Germany
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    • Lehrstuhl für Epidemiologieder LMU München am UNIKA-T Augsburg
    • Ms.  Professorin Dr. med.  Christine  Meisinger 
    • Neusässer Str. 47
    • 86156  Augsburg
    • Germany
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    • Lehrstuhl für Epidemiologieder LMU München am UNIKA-T Augsburg
    • Ms.  Marion  Kötzner 
    • Neusässer Str. 47
    • 86156  Augsburg
    • Germany
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Sources of Monetary or Material Support

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    • Lehrstuhl für Epidemiologieder LMU München am UNIKA-T Augsburg
    • Mr.  Professor Dr.  Jakob  Linseisen 
    • Neusässer Str. 47
    • 86156  Augsburg
    • Germany
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Status

  •   Recruiting ongoing
  •   [---]*
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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.