Investigation of the Effect of Concurrent Administration of Synbiotic Supplement and Vitamin D Supplement on Liver Disease Severity, Minimal Hepatic Encephalopathy, Quality of Life, Sleep, Mental Health, and Appetite in Patients with Liver Cirrhosis: A Double-Blind Randomized Clinical Trial

The aim of this study is to investigate the effect of concurrent administration of synbiotic and vitamin D supplements on liver disease severity, minimal hepatic encephalopathy, quality of life, sleep quality, mental health, and appetite in patients with liver cirrhosis.

A randomized controlled clinical trial with parallel groups, double-blind, phase 3, and the random sequence was generated using the website www.sealedenvelope.com. the final sample size was determined as 66 participants.

Patients with cirrhosis who meet the eligibility criteria and are referred to Motahari Clinic in Shiraz will enter a randomized double-blind clinical trial after obtaining informed consent, and they will be randomly allocated into two groups—intervention (vitamin D and synbiotic) and control (placebo)—for 8 weeks. The appearance and packaging of the supplement and placebo will be identical and coded, so that both the patient and the researcher are unaware of the type of intervention.

Inclusion criteria: Patients with liver cirrhosis with a definite diagnosis of cirrhosis and vitamin D deficiency (less than 30 ng/ml). Exclusion criteria: Receiving synbiotic, vitamin D, or antibiotics during the past 2 to 3 months.

Intervention group (A): Patients will receive a synbiotic and vitamin D for 8 weeks. Synbiotic: FamiLact 2 Plus (Zist Takhmir), 1 capsule daily after lunch. Vitamin D 50,000 IU (Zahravi): 1 capsule weekly. Control group (B): Patients will receive synbiotic placebo and vitamin D placebo for 8 weeks. FamiLact 2 Plus synbiotic placebo (starch) produced by Shiraz Faculty of Pharmacy: 1 capsule daily after lunch. Vitamin D placebo (paraffin) produced by Zahravi Pharmaceutical Company: 1 capsule weekly.

score of minimal hepatic encephalopathy؛ the severity of liver disease

Randomization was performed using block randomization with permuted blocks and variable block sizes of 4 and 6 and an allocation ratio of 1:1. The randomization sequence was generated using the website www.sealedenvelope.com . Considering approximately 10% dropout, the final sample size was determined as 66 participants, and they were allocated to the intervention and control groups based on this sequence.

Allocation Concealment Mechanism: To ensure blinding of all researchers and participants, a third individual who is not involved in conducting the study will prepare the random allocation list for assigning participants to the groups. This person will label all intervention containers—identical in appearance and color—based on coded numbering. Therefore, participants will remain unaware of the type of intervention they receive, and the random sequence will be unpredictable. Double-Blind Design: The study will be conducted in a double-blind manner: both the participants and the researcher will be unaware of the type of intervention administered. All supplements and placebos will be identical in shape, color, size, and packaging

Due to the confidential and sensitive nature of participants’ information, and in order to comply with research ethics and protect patient privacy, there is no plan to share individual participant data (IPD). All data will be used solely within the study protocol and under the supervision of the Ethics Committee.