Impact of Propionic Acid on Regulatory T Cell Function in Healthy Adults ( Pro-Health) (Pro-Health)

Impact of Propionic Acid on Regulatory T Cell Function in Healthy Adults.

Pro-Health is a single-center, double-blind, randomized and placebo-controlled intervention study in healthy adults. The investigators address the effect of a dietary food supplementation of propionic acid on the immune system and the function of the intestinal barrier in healhty adults.

Study Overview

• Status: Active, not recruiting
• Conditions: Healthy
• Intervention / Treatment: Other: Placebo; Dietary supplement: Sodium propionate

Detailed Description

Chronic inflammation is a major risk factor of cardiovascular disease progression in CKD, irrespective of confounding comorbidities. Based on current knowledge, microbially-derived metabolites such as short chain fatty acids (SCFA) play an important role in the regulation of chronic inflammatory processes in CKD patients. Patients with CKD are known to have reduced serum levels of the SCFA propionic acid (PA), as a consequence of both gut microbial dysbiosis and reduced fiber intake. In animal and human studies the impact of PA on function and abundance of regulatory T cells (Treg) has been demonstrated. Consequently, the investigators aim to increase the PA serum levels by oral PA food supplementation in healthy adults in order to perspectively intervene with the same strategy in patients with CKD in the near future, with the target to increase abundance and function of antiinflammatory cells.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 13353
    • Department of Pediatric Gastroenterology, Nephrology and Metabolic Diseases, Charité-Universitätsmedizin Berlin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 18 - 40 years old
• Body weight: > 30kg

Exclusion Criteria:

• Disease or dysfunctions, which disqualifies the patient
• Incapacity of contract or any other circumstances, which prohibit the patient from understanding setup, meaning and entity of the study
• Acute infections
• Immunosuppressive therapy within the last 12 weeks before the start of the study
• Pre-/pro- or postbiotic or antibiotic therapy within the last 4 weeks before the start of the study
• Planned or unplanned hospitalization within in last 4 weeks before the start of the study or during study
• Malignant diseases
• Pregnancy
• chronic gastrointestinal or hepatic diseases (for example chronic inflammatory bowel disease
• alcohol- or drug abuse
• parallel participation on other interventional trials

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo Intervention; The control-group receives a placebo instead of propionate. The placebo contains maltodextrin and the same amount of sodium chloride as compared to the PA intervention. The placebo is taken twice per day for 28 days.	Other: Placebo; The patients will be randomized to PA or placebo intervention (2:1 randomization). After the intervention of 28 days, we conduct an open-label study phase, where all patients are offered a dietary supplement of PA for overall 12 weeks (8 additional weeks for the intervention group and 12 weeks for the placebo group). By doing so we are giving every patient the opportunity to take PA and benefit from the possible positive impact on immunsystem and intestinal barrier function.
Experimental: PA Intervention.; The group which receives the PA as a dietary food supplement. A single capsule contains 500mg of sodiumpropionate, which is taken twice daily for 28 days.	Dietary supplement: Sodium propionate; The patients will be randomized to PA or placebo intervention (2:1 randomization). After the intervention of 28 days, we conduct an open-label study phase, where all patients are offered a dietary supplement of PA for overall 12 weeks (8 additional weeks for the intervention group and 12 weeks for the placebo group). By doing so we are giving every patient the opportunity to take PA and benefit from the possible positive impact on immunsystem and intestinal barrier function.; Other Names: Propicum

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in count of regulatory T-cells from baseline to week 4	Analysis of Treg counts in whole blood (absolute quantification) and peripheral blood	Baseline visit (week 0) in comparison to week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Single cell RNA sequencing of immune cells	Analysis of the transcriptome of immune cells using cellular indexing of transcriptomes and epitopes (CITEseq)	Baseline visit (week 0); Week 4
Taxonomy of the fecal microbiome	The taxonomy of the fecal microbiome will be anayzed using 16S RNA amplicon sequencing.	Baseline visit (week 0); Week 4
Measuring the suppressive function of regulatory T cells (Tregs) as percentage of proliferated conventional CD4-positive T cells with an in vitro T regulatory cell (Treg) suppression assay	The suppressive capacity of patients Treg will be analyzed by co-cultivation with conventional, stimulated T cells (Tconv) in different proportions (Treg:Tconv). The proliferation of Tconv will be reported.	Baseline visit (week 0); Week 4
Propionic acid serum levels and targeted metabolomics	Analysis of PA serum levels and other microbially-derived metabolites by GC-MS and LC-MS	Baseline visit (week 0); Week 2; Week 4
Relative abundance of different immune cell subsets with Immune cell phenotyping of peripheral blood mononuclear cells (PBMC)	Patients PBMC will be thawed and immune cells we be analyzed using multicolor flow cytometry and mass cytometry. By using a broad range of different antibodies combined in several panels the investigators will analyse distinct T cell subtypes including markers of activation, but also other immune cells (including B cells, dendritic cells, monocytes, natural killer cells). Data will reported in relation to parent populations (e.g. T heller cells in % of T cells).	Baseline visit (week 0); Week 2; Week 4
Measuring the intestinal barrier function by measuring the concentration of different leaky gut markers	Analysis of biomarkers for intestinal barrier function, such as sCD14, zonulin-1 and LPS	Baseline visit (week 0); Week 2; Week 4
Cardiovascular Phenothyping	Analysis of heart rate over time.	Baseline visit (week 0); Week 2; Week 4
Cardiovascular Phenotyping	Analysis of blood pressure over time.	Baseline visit (week 0); Week 2; Week 4
Cholesterol levels	Cholestrol levels will be assessed using standard clinical lab values	Baseline visit (week 0); Week 2; Week 4

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2024
• Primary Completion (Actual): February 28, 2024
• Study Completion (Estimated): May 30, 2025

Study Registration Dates

• First Submitted: December 27, 2023
• First Submitted That Met QC Criteria: December 27, 2023
• First Posted (Actual): January 10, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 14, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: EA2/195/22_2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No