Effects of Akkermansia Muciniphila and Berberine Supplementation on Insulin Sensitivity in Night-shift Workers (Shift2Health)

February 23, 2026 updated by: FH Joanneum Gesellschaft mbH

Effects of Akkermansia Muciniphila and Berberine Supplementation on Insulin Sensitivity in Night-shift Workers: a Double-blind, Randomised, Placebo-controlled, Crossover Study Within the Shift2Health Project

Night shift work is associated with an increased risk of obesity, insulin resistance, and cardiometabolic disorders, largely due to circadian misalignment, disrupted sleep, and altered eating patterns. These behavioral and physiological disturbances impair glucose metabolism and are further influenced by the gut microbiota. In particular, the bacterium Akkermansia muciniphila has been linked to improved metabolic health, including enhanced insulin sensitivity, lipid regulation, and maintenance of intestinal barrier integrity. Berberine, a bioactive plant-derived compound, has demonstrated metabolic benefits, including upregulation of A. muciniphila, improvement of insulin sensitivity, and modulation of lipid metabolism.

Together, these complementary mechanisms suggest that combined A. muciniphila supplementation and berberine administration may synergistically improve metabolic health in shift workers by targeting gut microbiota composition and circadian-regulated metabolic pathways.

Based on this rationale, a double-blind, randomized, placebo-controlled, crossover study is being conducted in 200 night-shift workers from healthcare and industrial sectors in Austria and Denmark. Participants are stratified by age, sex, and work sector and randomly assigned to intervention sequences. Each participant receives either the combined supplement or placebo for 12 weeks, followed by a four-week washout, after which the alternate intervention is administered for another 12 weeks, with a total participation of 28 weeks.

Assessments are performed at four study visits and include anthropometry, body composition, blood pressure, and collection of blood, urine, and feces. Participants complete validated questionnaires on dietary intake, lifestyle, work schedules, and general health to monitor behavioral patterns throughout the study. Dietary intake is recorded for four days prior to each sampling visit in consideration of shift schedules. Sleep duration and quality are monitored via diaries and actigraphy and aligned with dietary records. Circadian variation is minimized by standardizing sampling times and implementing a fasting and synchronization period prior to visits.

The primary outcome is insulin sensitivity, measured by HOMA-IR. Secondary exploratory outcomes include gut microbiota composition and diversity, biomarkers of intestinal permeability and inflammation, lipid profiles, body composition, sleep quality, and dietary behavior.

These measures collectively provide a comprehensive evaluation of the metabolic, microbiome, and circadian effects of combined A. muciniphila and berberine supplementation in night-shift workers.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
200

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Austria
    • Styria
      • Graz, Styria, Austria, 8020
        • Recruiting
        • FH JOANNEUM University of Applied Sciences
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Health care or industrial shift worker
  • Employed or self-employed working ≥ 24 h/week
  • Current night shift work (night shift defined as a work schedule that includes at least 3 hours of work between 00:00 and 5:00) with at least 2 consecutive nights/month
  • Night shift work duration > 3 years
  • 4 or more night shifts/month

Exclusion Criteria:

  • BMI of 40 kg/m² or higher
  • Pregnancy or planned pregnancy within 6 months of enrolment or breastfeeding women
  • Bariatric surgery
  • Surgery in the 3 months prior to the study or planned surgery in the next 6 months that, in the opinion of the investigators, could potentially affect the outcome of the study
  • Diagnosed diabetes type 1 or type 2
  • Uncontrolled thyroid disease (confirmed by clinically significant abnormal TSH/T4 levels without stable medication for more than 3 months)
  • Chronic diseases (renal failure, active hepatitis, liver cirrhosis, myocardial infarction within the last 2 years, stroke, chronic obstructive pulmonary disease or cancer)
  • Immunodeficiency syndrome, active autoimmune or autoinflammatory disease (e.g. multiple sclerosis, lupus, rheumatoid arthritis), inflammatory bowel disease (e.g. IBS or ulcerative colitis) and acute episodes of atopic diseases (atopic dermatitis, asthma, type 1 allergies such as hay fever). Grave's disease, Hashimoto thyroiditis, Celiac disease, sarcoidosis, Lichen planus, are allowed, if well treated and stable
  • Regular intake of anticoagulants
  • Known allergy to any inactive or active ingredients in the study products
  • Participation in other clinical intervention trials during the study
  • Current or planned participation in a weight loss program (including intermittent fasting), extreme diet, or vigorous exercise (e.g., running, fast cycling, swimming laps, or playing intense sports that quickly raise your heart rate)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: AB Group
Participants will first receive Verum (A) for 3 months. After a 4-week washout period, they will receive Placebo (B) for 3 months.
Dietary supplement: Verum (A)
1 capsule of A. muciniphila (pasteurized, initial quantity of 10^30 TFU, heat inactivated) and 1 capsule of 500 mg berberine hydrochloride per day.
Dietary supplement: Placebo (B)
1 capsule of A. muciniphila placebo and 1 capsule of berberine placebo (both identical to verum regarding the shape, size, colour, and matched in excipients) per day.
Experimental: BA Group
Participants will first receive Placbo (B) for 3 months. After a 4-week washout period, they will receive Verum (A) for 3 months.
Dietary supplement: Verum (A)
1 capsule of A. muciniphila (pasteurized, initial quantity of 10^30 TFU, heat inactivated) and 1 capsule of 500 mg berberine hydrochloride per day.
Dietary supplement: Placebo (B)
1 capsule of A. muciniphila placebo and 1 capsule of berberine placebo (both identical to verum regarding the shape, size, colour, and matched in excipients) per day.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change of 3-months supplementation with A. muciniphila and berberine on insulin resistance using HOMA-IR compared to placebo
Time Frame: At the beginning and the end of each intervention period (week 0, 12, 16, 28)
Homeostasis Model Assessment of Insulin Resistance, calculated as (fasting insulin (μU/ml) x fasting glucose (mmol/l)) / 22.5, will be assessed to calculate the change between baseline and endpoint in the two periods
At the beginning and the end of each intervention period (week 0, 12, 16, 28)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in gut microbiom composition between the baseline and endpoint change in the two periods
Time Frame: At the beginning and the end of each intervention period (week 0, 12, 16, 28)
Gene sequencing of the 16S rRNA is performed on the stool samples to compare microbiota diversity and relative abundance
At the beginning and the end of each intervention period (week 0, 12, 16, 28)
Change in FABPi between the baseline and endpoint change in the two periods
Time Frame: At the beginning and the end of each intervention period (week 0, 12, 16, 28)
Measurement of FABP intestinal (FABPi) in blood (pg/mL)
At the beginning and the end of each intervention period (week 0, 12, 16, 28)
Change in zonulin between the baseline and endpoint change in the two periods
Time Frame: At the beginning and the end of each intervention period (week 0, 12, 16, 28)
Measurement of zonulin in blood (ng/mL)
At the beginning and the end of each intervention period (week 0, 12, 16, 28)
Change in LPB between the baseline and endpoint change in the two periods
Time Frame: At the beginning and the end of each intervention period (week 0, 12, 16, 28)
Measurement of lipopolysaccharide-binding protein (LPB) in blood (pg/mL)
At the beginning and the end of each intervention period (week 0, 12, 16, 28)
Change in CRP between the baseline and endpoint change in the two periods
Time Frame: At the beginning and the end of each intervention period (week 0, 12, 16, 28)
Analysis of high-sensitive C-reactive protein (hs-CRP, mg/L) in blood
At the beginning and the end of each intervention period (week 0, 12, 16, 28)
Change in stool short-chain fatty acids (SCFA) between the baseline and endpoint change in the two periods
Time Frame: At the beginning and the end of each intervention period (week 0, 12, 16, 28)
SCFA will be extracted and quantitatively analysed by GC-MS (µmol/g)
At the beginning and the end of each intervention period (week 0, 12, 16, 28)
Change in blood lipid profile and cardiovascular markers between the baseline and endpoint change in the two periods
Time Frame: At the beginning and the end of each intervention period (week 0, 12, 16, 28)
Measurement of cholesterol (mmol/L), low-density lipoprotein cholesterol (LDL-C, mmol/L), high-density lipoprotein (HDL-C, mmol/L), and triglyceride levels (TG, mmol/L) in blood
At the beginning and the end of each intervention period (week 0, 12, 16, 28)
Change in blood pressure between the baseline and endpoint change in the two periods
Time Frame: At the beginning and the end of each intervention period (week 0, 12, 16, 28)
Systolic BP (mmHG) and diastolic BP (mmHG)
At the beginning and the end of each intervention period (week 0, 12, 16, 28)
Change in melatonin between the baseline and endpoint change in the two periods
Time Frame: At the beginning and the end of each intervention period (week 0, 12, 16, 28)
6-sulfatoxymelatonin in urine (µg/L)
At the beginning and the end of each intervention period (week 0, 12, 16, 28)
Change in BMI between the baseline and endpoint change in the two periods
Time Frame: At the beginning and the end of each intervention period (week 0, 12, 16, 28)
Body mass index (BMI)
At the beginning and the end of each intervention period (week 0, 12, 16, 28)
Change in body composition between the baseline and endpoint change in the two periods
Time Frame: At the beginning and the end of each intervention period (week 0, 12, 16, 28)
Bioelectrical Impedance Analysis (BIA)
At the beginning and the end of each intervention period (week 0, 12, 16, 28)
Change in metabolomics at the end of the two periods
Time Frame: At the beginning and the end of each intervention period (week 12, week 28)
Metabolomic profiles obtained with LC-MS/MS
At the beginning and the end of each intervention period (week 12, week 28)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
FH Joanneum Gesellschaft mbH

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Medical University of Vienna
Erasmus Medical Center
University of Vienna
Københavns Universitet

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 20, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 1, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 27, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 23, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 27, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 27, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 23, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 1306/2025
  • 101080788 (Other Grant/Funding Number: Horizon Europe)

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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