Metabolic health and liver disease in Polish twins

Multimorbidity in Metabolic Syndrome: A Longitudinal Cohort Study in TWINS.PL

This project will follow Polish twins aged 15–44 for five years to see if family history, prior COVID-19, or other factors predict new fatty liver (MASLD), liver fibrosis/cirrhosis, or other metabolic syndrome complications.

Quick facts

• Study type: Observational
• Enrollment: 1500 (estimated)
• Ages: 15 Years to 44 Years
• Sex: All
• Sponsor: Poznan University of Medical Sciences (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Poznan, Wielkopolska)
• Trial ID: NCT07181018 on ClinicalTrials.gov

What this trial studies

This is a five-year observational cohort using a trial-within-cohort design to document new cases and progression of MASLD, liver fibrosis, cirrhosis, and other metabolic syndrome complications among Polish twins aged 15–44. Twin pairs with a living co-twin who provide informed consent will contribute medical and family histories and undergo periodic clinical exams, laboratory testing, and liver imaging to track incident disease and progression. The protocol excludes participants with pre-existing advanced liver disease, specific genetic or autoimmune liver disorders, high chronic alcohol intake, or inability to provide family medical history. The study will also analyze whether prior COVID-19 infection or long-COVID features are associated with onset or worsening of MASLD and related metabolic conditions.

Who should consider this trial

Good fit: Ideal candidates are Polish twins aged 15–44 who have a living co-twin, can provide informed consent and family medical history, and have first- or second-degree relatives with metabolic syndrome or related conditions.

Not a fit: People with pre-existing advanced liver fibrosis, cirrhosis, liver cancer, specified genetic or autoimmune liver diseases, high chronic alcohol intake, or without a consenting co-twin are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, the study could help identify high-risk individuals and inform earlier screening and prevention to reduce progression to MASLD, fibrosis, or cirrhosis.

How similar studies have performed: Prior twin and cohort studies have linked genetics and family history to metabolic syndrome and fatty liver, while the specific link between prior COVID-19 and MASLD progression is a newer and less-established area of research.

Eligibility criteria

Inclusion Criteria

1\. Age between 15 and 44 years. 2. Provision of informed consent to participate in the study. 3. Twin with a living co-twin. 4. Positive family history in first- and second-degree relatives of metabolic syndrome (MS), associated diseases, or the most common complications of the syndrome.

\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ Exclusion Criteria

Permanent exclusion criteria:

1. Co-twin does not consent to participate in the study.
2. Inability to obtain medical history of biological family members.
3. Presence of advanced liver fibrosis, cirrhosis, or liver cancer.
4. Known liver genetic disorders, autoimmune hepatitis, celiac disease, hemochromatosis, primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), cystic fibrosis, or Wilson's disease.
5. Current or chronic alcohol consumption \>20 g of ethanol/day in women and \>30 g/day in men.
6. Short bowel syndrome.
7. Cyanotic congenital heart defect.
8. Myasthenia.
9. Central nervous system degenerative diseases such as Alzheimer's disease, Parkinson's disease, or Huntington's disease.
10. Storage diseases involving the liver.
11. Active malignant neoplasm undergoing treatment (excluding non-melanoma skin cancers and melanoma treated non-pharmacologically).
12. Chronic kidney disease requiring renal replacement therapy.
13. Status post organ or tissue transplantation requiring immunosuppression.
14. Pituitary, hypothalamic, or adrenal hyperfunction/hypofunction requiring hormone supplementation.
15. Addiction to psychoactive substances or drugs.
16. Other severe and incurable diseases that, in the investigator's opinion, constitute a permanent contraindication for participation in the study.
17. Lack of cooperation by the volunteer during the visit to the Research Center. \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_

Temporary exclusion criteria (after resolution, the volunteer may be enrolled):

1. Acute infection, low-grade fever or fever, or use of antibiotics at the time of recruitment or prior to the visit at the Research Center - inclusion possible after 6 weeks.
2. Any vaccination within the past 6 weeks.
3. Pregnancy and up to 6 months postpartum.
4. 3 months after the natural cessation of breastfeeding.
5. 3 months after surgery (does not apply to minor surgical procedures).
6. Untreated hyperthyroidism or hypothyroidism - inclusion possible 3 months after achieving euthyroidism.
7. Significant weight loss or gain in the past 3 months (\>10% of initial body weight) - inclusion possible 3 months after weight stabilization.
8. 6 months after discontinuation of temporary parenteral or enteral nutrition via feeding tube.
9. 12 months after bariatric surgery.
10. Systemic treatment with steroids, chemotherapy, immunosuppressive drugs, or biological therapy known to be hepatotoxic or potentially inducing abnormalities found in MS - inclusion possible at least 3 months after completing therapy.

Where this trial is running

Poznan, Wielkopolska

• Uniwersytecki Szpital Kliniczny — Poznan, Wielkopolska, Poland (Recruiting)

Study contacts

• Study coordinator: Piotr Eder, MD, Profesor

Conditions Twins; Metabolic Syndrome