Accelerating Recovery After ICU Admission: Post-discharge Supplementation With Pasteurized Akkermansia Muciniphila. (PAM-ICU)

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

Study Overview

• Status: Not yet recruiting
• Conditions: Sepsis; Critical Illness; Post Intensive Care Unit Syndrome; Intensive Care Unit Survivors; Microbiome Dysbiosis
• Intervention / Treatment: Dietary supplement: Pasteurized Akkermansia muciniphila; Other: Placebo Control

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Duveke de Gaay Fortman, MD; Phone Number: +31205669111; Email: p.d.e.degaayfortman@amsterdamumc.nl
• Study Contact Backup: Name: Rebekka Bout; Phone Number: +31205669111; Email: r.rebel@amsterdamumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pasteurized Akkermansia muciniphila (PAM); Oral supplementation with pasteurized Akkermansia muciniphila, 30 × 10⁹ bacteria in capsule form, once daily for 56 days, in addition to standard care.	Dietary supplement: Pasteurized Akkermansia muciniphila; Oral supplementation with pasteurized Akkermansia muciniphila, 30 × 10⁹ bacteria in capsule form, once daily for 56 days, in addition to standard care.
Placebo Comparator: Placebo; 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.	Other: Placebo 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in abundance of butyrate-producing bacteria	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	Baseline and day 56
Safety (occurrence of adverse events)	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	Baseline to day 56 (end of intervention)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in gut microbiota composition	Differences between arms and within-participant change from baseline in microbiota α-diversity and β-diversity	Day 0 (baseline), day 28, day 56
Changes in circulating immune and inflammatory profiles	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.	Day 0 (baseline), day 28, day 56
Changes in gut barrier markers	Plasma levels and changes from baseline of lipopolysaccharide-binding protein (LBP) and soluble CD14 (sCD14); between-arm comparisons.	Day 0 (baseline), day 28, day 56
Secondary infections and rehospitalizations	Incidence of adjudicated secondary infections and all-cause rehospitalizations; comparison between PAM and placebo.	Through day 365

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Host metabolic function	Change from baseline in insulin sensitivity estimated by HOMA-%S, calculated from fasting plasma glucose and insulin; between-arm differences.	Day 0 (baseline), day 28, day 56

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Collaborators: ZonMw: The Netherlands Organisation for Health Research and Development; THE AKKERMANSIA COMPANY
• Investigators: Principal Investigator: JW Wiersinga, Professor, Amsterdam UMC

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: December 8, 2025
• First Submitted That Met QC Criteria: December 8, 2025
• First Posted (Actual): December 19, 2025

Study Record Updates

• Last Update Posted (Actual): December 19, 2025
• Last Update Submitted That Met QC Criteria: December 8, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Microbiome; Randomized Controlled Trial; PAM; Akkermansia muciniphila; Gut Barrier Function; Pasteurized Akkermansia muciniphila; Postbioticum; Post-Sepsis Recovery
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathological Conditions, Signs and Symptoms; Critical Illness; Sepsis
• Other Study ID Numbers: NL-009844

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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