Characterization of nutritional, AhR-dependent immune responses in patients with chronic kidney disease and multiple sclerosis
Organizational Data
- DRKS-ID:
- DRKS00030864
- Recruitment Status:
- Recruiting ongoing
- Date of registration in DRKS:
- 2022-12-07
- Last update in DRKS:
- 2024-03-12
- Registration type:
- Prospective
Acronym/abbreviation of the study
TAhRget
URL of the study
No Entry
Brief summary in lay language
An unfavorable Western diet rich in salt, saturated fat, and processed animal products is considered an independent risk factor for the development of chronic kidney disease (CKD) and multiple sclerosis (MS) and promotes the progression of both diseases. On the other hand, a whole-food, plant-based diet is associated with better progression. However, the underlying mechanisms are poorly understood and may be mediated in part by the aryl hydrocarbon receptor (AhR). Therefore, we intend to characterize the diet-dependent AhR-mediated mechanisms in patients with CKD and MS. We postulate that disease-specific nutritional approaches may reduce AhR-mediated inflammation.
Brief summary in scientific language
The present study is a subproject of an interdisciplinary network for the investigation of pathomechanisms, which is funded by the BMBF. Overall aim of the TAhRget network: Inflammation-related organ damage is a major pathological factor of chronic diseases such as CKD and MS. The AhR is a Ligand-activated transcription factor that is activated by a variety of ligands. These diverse ligands are found in the environment and diet or are produced by bacteria in the gut. AhR appears to be involved in immune dysregulation in CKD and MS, interestingly, however, in opposite ways. Whereas in CKD there is over-activation of the AhR due to the reduced ability to excrete ligands via the urine, in MS a lack of ligands appears to be associated with increased inflammatory and disease activity. We would like to use this phenomenon to elucidate the mechanisms of AhR-mediated immune responses as a cross-disease pathomechanism and thus contribute to the development of targeted AhR therapy strategies for the adjunctive treatment of for the adjunctive treatment of CKD and MS.
Health condition or problem studied
- ICD10:
- N18 - Chronic kidney disease
- ICD10:
- G35 - Multiple sclerosis
- Healthy volunteers:
- No
Interventions, Observational Groups
- Arm 1:
- This is an exploratory, mechanistic study in which patients will consume a balanced, standardized, plant-based diet for five days (exposure). There will be a total of five study time points: two baselines 2 weeks apart (V1, V2), day 3 of exposure (V3), after 5 days of exposure (V4), 4 weeks post exposure (V5). Screening (V0) In order to document the health status of the patients, the following parameters will be collected before inclusion in the study: Medical history, physical examination, body weight, body height, hip and waist circumference, blood pressure, electrocardiogram, heart rate, routine laboratory parameters from blood and urine. Study visits (V1-V5) During the study visits, body weight and body composition are determined. Also, blood pressure, pulse and pulse wave velocity are measured and biomaterials (blood, 24h urine, stool) are collected. The dietary habits of the last four weeks will be recorded once at V1 with an established dietary frequency questionnaire of the Robert Koch Institute (RKI). At V2, the patients are given the food for days 1-3, and at V3 the food for days 4-5.
Endpoints
- Primary outcome:
- Serum activation potential of AhR measured in vitro using a cell-based assay with AhR reporter cells.
- Secondary outcome:
- - Reduction of systolic and diastolic blood pressure - Decrease in pulse wave velocity (PWV) - Change in taxonomic and functional composition of the gut microbiota - Alteration of mRNA expression of AhR-specific genes in whole blood - Change in metabolite patterns in serum, stool, and 24h urine - Change in tryptophan metabolites, amino acids and related amines, short chain fatty acids, purines, fatty acid profiles and fatty acid methyl esters in plasma, stool and 24h urine - Altered abundances of pro- and anti-inflammatory immune cells - Increase of anti-inflammatory circulating cytokines in plasma - Change in the expression of bacterial genes responsible for enzymes for the formation of metabolites that are relevant to host health - Improved intestinal barrier function
Study Design
- Purpose:
- Treatment
- Allocation:
- N/A (single arm study)
- Control:
-
- Uncontrolled/single arm
- Phase:
- N/A
- Study type:
- Interventional
- Mechanism of allocation concealment:
- No Entry
- Blinding:
- No
- Assignment:
- Single (group)
- Sequence generation:
- No Entry
- Who is blinded:
- No Entry
Recruitment
- Recruitment Status:
- Recruiting ongoing
- Reason if recruiting stopped or withdrawn:
- No Entry
Recruitment Locations
- Recruitment countries:
-
- Germany
- Number of study centers:
- Monocenter study
- Recruitment location(s):
-
- University medical center Charité - Universitätsmedizin Berlin Berlin
Recruitment period and number of participants
- Planned study start date:
- 2023-04-17
- Actual study start date:
- 2023-04-12
- Planned study completion date:
- 2024-11-01
- Actual Study Completion Date:
- No Entry
- Target Sample Size:
- 24
- Final Sample Size:
- No Entry
Inclusion Criteria
- Sex:
- All
- Minimum Age:
- 18 Years
- Maximum Age:
- 60 Years
- Additional Inclusion Criteria:
- For all patients: - Men and women in a 1:1 ratio - Age 18-60 years - Body Mass Index 18,5 - 29,9 kg/m2 - Stool frequency every 1-2 days - Ability to consent - Existing health insurance CKD patients: - Chronic renal failure stage 3 (GFR 30- 59 ml/min) - Polycystic kidney disease For MS patients: - Relapsing-remitting MS according to MS diagnosis according to McDonald 2017 - EDSS smaller than 4.5 - Stable immunomodulatory therapy or no immunomodulatory therapy min. 6 months prior to inclusion
Exclusion Criteria
For all patients: - Diseases or functional disorders that, in the opinion of the study physician, preclude participation in the study - Autoimmune diseases (except MS) - Diabetes mellitus type 2 - Postoperative phase - Acute infection - Malnutrition - Smoker (abstinence for at least 6 months) - Vegetarian - vegans - Food intolerances - Food allergies - Taking antibiotics within the last 3 months - Regular intake of probiotics and/or prebiotics - Change in body weight of more than 2 kg in the previous month of the study - Pregnancy and lactation - Known medication, drug or alcohol abuse - Incapacity or other circumstances that do not allow the patient to fully understand the nature, meaning and implications of this study. For CKD patients: - CKD due to other underlying diseases, e.g., diabetes, glomerulonephritis For MS patients: - Initiation of or change in immunomodulatory therapy during the study - Cortisone treatment in the last 30 days before inclusion - Relapse in the last 30 days before inclusion
Addresses
Primary Sponsor
- Address:
- Charité - Universitätsmedizin Berlin10117 BerlinGermany
- Telephone:
- No Entry
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
- Investigator Sponsored/Initiated Trial (IST/IIT):
- Yes
Contact for Scientific Queries
- Address:
- Charité - Universitätsmedizin BerlinDr. rer. medic. Anja MählerLindenberger Weg 8013125 BerlinGermany
- Telephone:
- +49 30 450540323
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
Contact for Public Queries
- Address:
- Charité - Universitätsmedizin BerlinDr. rer. medic. Anja MählerLindenberger Weg 8013125 BerlinGermany
- Telephone:
- +49 30 450540323
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
Principal Investigator
- Address:
- Charité - Universitätsmedizin BerlinDr. rer. medic. Anja MählerLindenberger Weg 8013125 BerlinGermany
- Telephone:
- +49 30 450540323
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
Sources of Monetary or Material Support
Public funding institutions financed by tax money/Government funding body (German Research Foundation (DFG), Federal Ministry of Education and Research (BMBF), etc.)
- Address:
- Bundesministerium für Bildung und Forschung10117 BerlinGermany
- Telephone:
- No Entry
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
Ethics Committee
Address Ethics Committee
- Address:
- Ethikkommission der Charité – Universitätsmedizin BerlinCharitéplatz 110117 BerlinGermany
- Telephone:
- (+49)30-450517222
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
Vote of leading Ethics Committee
- Vote of leading Ethics Committee
- Date of ethics committee application:
- 2022-10-19
- Ethics committee number:
- EA4/168/22
- Vote of the Ethics Committee:
- Approved
- Date of the vote:
- 2022-11-16
Further identification numbers
- Other primary registry ID:
- No Entry
- EudraCT Number:
- No Entry
IPD - Individual Participant Data
- Do you plan to make participant-related data (IPD) available to other researchers in an anonymized form?:
- Yes
- IPD Sharing Plan:
- Plan Description: Individual participant data that underlie the results of reported articles (text, tables, figures, supplemental data) will be shared after deidentification. Time Frame: Beginning 9 months and ending 36 months following article publication. Access Criteria: Researchers who provide a methodologically sound proposal.
Study protocol and other study documents
- Study protocols:
- No Entry
- Study abstract:
- No Entry
- Other study documents:
- No Entry
- Background literature:
- No Entry
- Related DRKS studies:
- No Entry
Publication of study results
- Planned publication:
- No Entry
- Publikationen/Studienergebnisse:
- No Entry
- Date of first publication of study results:
- No Entry
- DRKS entry published for the first time with results:
- No Entry
Basic reporting
- Basic Reporting / Results tables:
- No Entry
- Brief summary of results:
- No Entry