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

Styrian Higher Education

Status: Enrolling

Conditions: Gut Microbiota Modulation; Obesity & Overweight; Circadian Rhythm Disorders; Prediabetes (Insulin Resistance, Impaired Glucose Tolerance)

Treatments: Dietary Supplement: Verum (A); Dietary Supplement: Placebo (B)

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT07440147

1306/2025

101080788 (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Enrollment: 200 estimated patients

Sex: All

Ages: 21+ years old

Volunteers: Accepts Healthy Volunteers

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)

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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200 participants in 2 patient groups

AB Group

Experimental group

Description:

Participants will first receive Verum (A) for 3 months. After a 4-week washout period, they will receive Placebo (B) for 3 months.

Treatment:

Dietary Supplement: Placebo (B)

Dietary Supplement: Verum (A)

BA Group

Experimental group

Description:

Participants will first receive Placbo (B) for 3 months. After a 4-week washout period, they will receive Verum (A) for 3 months.

Treatment:

Dietary Supplement: Placebo (B)

Dietary Supplement: Verum (A)