Critical Illness, Intensive Care Unit Survivors, Microbiome Dysbiosis, Post Intensive Care Unit Syndrome, Sepsis
Conditions
Keywords
Pasteurized Akkermansia muciniphila, Akkermansia muciniphila, Postbioticum, Microbiome, PAM, Gut Barrier Function, Post-Sepsis Recovery, Randomized Controlled Trial
Brief summary
The goal of this clinical trial is to learn if daily oral supplementation with pasteurized Akkermansia muciniphila (PAM), an EFSA-approved food supplement, can support recovery in adults who have recently been treated in the ICU for sepsis. The main questions it aims to answer are: * Is PAM safe to take for 56 days after ICU discharge? * Does PAM increase the abundance of beneficial butyrate-producing bacteria in the gut? Researchers will compare PAM to a placebo (a capsule that looks the same but has no active ingredient) to see if PAM improves gut microbiota and immune recovery. Participants will: * Take PAM or placebo capsules once daily for 56 days * Provide stool and blood samples at baseline, day 28, and day 56 * Receive a follow-up phone call about their health 1 year after starting the study
Interventions
DIETARY_SUPPLEMENTPasteurized Akkermansia muciniphila
Oral supplementation with pasteurized Akkermansia muciniphila, 30 × 10⁹ bacteria in capsule form, once daily for 56 days, in addition to standard care.
OTHERPlacebo Control
Oral administration of placebo capsules matched in appearance and dosing schedule to the PAM capsules, once daily for 56 days, in addition to standard care. The placebo contains no active component.
Sponsors
THE AKKERMANSIA COMPANY
ZonMw: The Netherlands Organisation for Health Research and Development
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
This is a double-blind, placebo-controlled trial. Participants, care providers, investigators, and outcomes assessors are masked to intervention assignment.
Intervention model description
Participants will be randomized in a parallel-group design to receive either pasteurized Akkermansia muciniphila supplementation or placebo.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥18 years * Treated in the ICU for at least 2 days and discharged to a regular clinical ward * Diagnosed with sepsis during ICU admission * Received selective digestive decontamination (SDD) or cephalosporin * Capable of giving written informed consent
Exclusion criteria
* Recent major gastrointestinal surgery * Diagnosed with ulcerative colitis or Crohn's disease * Presence of a hematological malignancy and/or current use of immunomodulatory therapy (e.g., CAR-T cell therapy or immune checkpoint inhibitors) Use of systemic immunomodulatory drugs or corticosteroids (defined as ≥10 mg prednisone equivalent daily at ICU discharge), at the time of inclusion. * History of solid organ or stem cell transplantation * Pregnancy or lactation * Donation of blood or plasma within 30 days prior to inclusion or planned donation during the intervention period * Any other condition that, in the opinion of the investigator, could pose a risk to the subject or interfere with study result
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety (occurrence of adverse events) | Baseline to day 56 (end of intervention) | Proportion of participants with ≥1 adverse event (AE) and total AE count, summarized by severity and relatedness, comparing PAM vs placebo at end of intervention |
| Change in abundance of butyrate-producing bacteria | Baseline and day 56 | Difference (Δ) from baseline in the relative abundance of gut butyrate-producing bacteria at day 56, assessed by shotgun metagenomic sequencing (taxa/functional pathways associated with butyrate production), comparing PAM vs placebo at the end of the intervention |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in circulating immune and inflammatory profiles | Day 0 (baseline), day 28, day 56 | Between-arm differences and longitudinal changes in systemic immune profiles, including major innate and adaptive subsets and activation markers. In addition, ex vivo whole blood stimulations will be performed to quantify cytokine production in response to microbial ligands. |
| Secondary infections and rehospitalizations | Through day 365 | Incidence of adjudicated secondary infections and all-cause rehospitalizations; comparison between PAM and placebo. |
| Changes in gut barrier markers | Day 0 (baseline), day 28, day 56 | Plasma levels and changes from baseline of lipopolysaccharide-binding protein (LBP) and soluble CD14 (sCD14); between-arm comparisons. |
| Changes in gut microbiota composition | Day 0 (baseline), day 28, day 56 | Differences between arms and within-participant change from baseline in microbiota α-diversity and β-diversity |
Other
| Measure | Time frame | Description |
|---|---|---|
| Host metabolic function | Day 0 (baseline), day 28, day 56 | Change from baseline in insulin sensitivity estimated by HOMA-%S, calculated from fasting plasma glucose and insulin; between-arm differences. |
Contacts
Primary ContactDuveke de Gaay Fortman, MD
Backup ContactRebekka Bout
Outcome results
None listed