Pea Fibre in Hemodialysis

Official title

Influencing Microbiota and Uremic Toxins With Pea Fibre Intervention in Nephrology

Overview

Background and problem Chronic kidney disease (CKD) affects a large share of adults worldwide and is a growing public-health concern. People with advanced CKD can develop "uremia", a dangerous build-up of waste products in the blood that the failing kidneys cannot remove. Even when patients receive regular dialysis, many so-called "uremic toxins" remain in the body because some of these substances bind tightly to blood proteins and are poorly removed by dialysis. Over 100 uremic toxins have been identified and classified and protein-bound toxins such as Indoxylsulfate and p-Cresylsulfate are especially difficult to clear by dialysis. Some uremic toxins are linked to heart and blood-vessel disease, inflammation, and worse outcomes in dialysis patients. For example, Indoxylsulfate has been associated with higher mortality, vascular calcification, vessel stiffness and heart failure. Reducing these toxins might therefore improve quality of life and lower cardiovascular risk in people on dialysis. Purpose of the study The study will test whether adding inner, fermentable pea fiber (a natural prebiotic) to the daily diet of hemodialysis patients can lower blood levels of uremic toxins-especially Indoxylsulfate-and improve related markers of inflammation and cardiovascular risk. The investigators hypothesize that fermentable fibers change gut bacterial composition so that less toxin-forming bacterial metabolism (from amino acids like tryptophan) occurs, thereby reducing the amount of harmful metabolites that reach the blood. Type of study: Randomized, double-blind, controlled trial with two groups. Duration: 8 weeks of intervention. Intervention: Participants will receive daily baked goods (bread, rolls, muffins, scones, pizza bread) that together provide 20 g of pea fiber per day; the control group will receive identical foods without added pea fiber. The fiber mix uses commercially available inner pea-fiber products. Blood and stool sampling: Blood samples are taken before the intervention, at 4 weeks and at 8 weeks to measure Indoxylsulfate and other toxins, inflammation markers, vitamin D metabolites and cardiovascular risk markers. A subgroup will also provide stool samples to study changes in the gut microbiome. Who can join Adults aged 18-89 who have been on chronic hemodialysis for at least three months and receive dialysis two to three times per week are eligible. The study excludes people with recent serious infections, advanced liver disease, active cancer, recent blood transfusion, pregnancy, certain food intolerances or inability to consent. Each study arm will include 36 participants. Primary and secondary outcomes Primary outcome: Change in blood Indoxylsulfate concentration between the pea-fiber group and the control group. Secondary outcomes: Levels of other uremic toxins, routine kidney-related blood tests (creatinine, urea, uric acid), electrolytes, vitamin D metabolites, inflammatory markers, lipid markers, FGF23, short-chain fatty acids, sKlotho, and the effect of patient serum on cytokine production in a standard immune cell line. Stool analyses in a subgroup will examine shifts in bacterial groups and metabolic networks. How the intervention is delivered and monitored Foods are prepared in a certified bakery and coded so neither participants nor study staff know who receives pea fiber or placebo. To improve adherence, participants choose from a variety of pre-portioned baked items and are advised to spread intake across the day. Unused portions are returned and logged. Dietary recalls and symptom questionnaires are collected to monitor changes in overall diet, appetite and gastrointestinal side effects. Blood draws are timed before dialysis after the long interdialytic interval to standardize measurements. Potential impact and limitations If fermentable inner pea fibers lower Indoxylsulfate and related toxins, this would support a simple, food-based strategy to reduce toxin burden and possibly cardiovascular risk in dialysis patients. However, previous studies show mixed results depending on the type of fiber used: fermentable fibers (like amylose-rich starch or inulin) have produced beneficial changes in some trials, while non-fermentable fibers did not. Since evidence high-quality randomized trials in dialysis patients is still limited there is the need for this study.

Interventions

• Dietary supplement praebiotic inner fermentable pea fibres
  prebiotic pea fibres baked into bread, rolls, muffins, scones or pizza bread in the intervention group.
• Dietary supplement Control
  Similar baked goods without prebiotic ingredients.

Primary outcome measures

• Indoxylsulfate plasma concentration [Time frame: 8 weeks]

Secondary outcome measures (9)

• p-cresyl sulfate plasma concentration [Time frame: 8 weeks]
• Trimethylamin-N-oxide plasma concentration [Time frame: 8 weeks]
• Tumor necrosis factor alpha plasma concentration [Time frame: 8 weeks]
• Interleukin-6 plasma concentration [Time frame: 8 weeks]
• C-reactive protein plasma concentration [Time frame: 8 weeks]
• Fibroblast growth factor 23 plasma concentration [Time frame: 8 weeks]
• Total plasma cholesterol concentration [Time frame: 8 weeks]
• LDL cholesterol plasma concentration [Time frame: 8 weeks]
• Triglyceride plasma concentration [Time frame: 8 weeks]

Eligibility criteria

Inclusion criteria

• male and female patients 18-89 years of age
• chronic hemodialysis treatment minimum 3 months for any kind of kidney disease
• 2-3 hemodialysis sessions per week
• expected to continue regular treatment for at least 3 months
• written informed consent

Exclusion criteria

• Persons younger than 18 or older than 89 years
• Clinically relevant infections at the time of the study or within 2 weeks prior to study inclusion
• Use of immunosuppressive medications, with the exception of glucocorticoids ≤ 5 mg prednisolone equivalent
• Liver cirrhosis, Child-Pugh stage C
• Active malignancy, with or without specific oncological therapy
• Blood transfusion within 4 weeks prior to inclusion, or severe anemia with a current indication for blood transfusion
• Planned absence (e.g., vacation) for more than 1 week during the study period
• Pregnancy
• Intolerance to gluten, eggs, milk, yeast, nuts, or pea protein
• Missing consent to participate in the study
• Inability to understand the study content and procedures and to provide informed consent after appropriate explanation
• Persons institutionalized by court or administrative order
• Simultaneous participation in another interventional study

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Prevention

Study locations

Germany · 1 center

• University Hospital Martin-Luther-University Halle-Wittenberg — Halle

Identifiers

NCT: NCT07544797 · UKH-KIMII-001-26

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗