Impact of Lifestyle Interventions on Cognitive Decline in Non-alcoholic Fatty Liver Disease

Official title

Impact of Lifestyle Interventions on Cognitive Decline in NAFLD: A Randomized Controlled Trial of Liver Fibrosis, Hormonal Imbalance, and Inflammatory Markers

Overview

This study investigates whether a structured lifestyle program can help improve thinking skills and liver health in adults with Non-Alcoholic Fatty Liver Disease (NAFLD). We are enrolling 45 participants, aged 18-42, who will be randomly assigned to one of three groups for six months: one receiving general health advice, a second following a supervised Mediterranean diet plan, and a third combining the same diet with a regular walking program. The main goal is to see if these diet and exercise interventions can lead to better scores on memory and reasoning tests, reduce liver stiffness measured by a painless scan (FibroScan), and improve related blood markers of inflammation and hormone balance.

Detailed description

This is a parallel-group, randomized controlled trial designed to evaluate the impact of lifestyle interventions on cognitive function in patients with NAFLD, and to explore associations with liver fibrosis severity and underlying biomarkers. The study aims to recruit 45 participants with imaging-confirmed NAFLD, who will be randomized (1:1:1) into a control group (general advice), a dietary intervention group (structured Mediterranean diet), or a combined intervention group (diet plus supervised exercise). Primary outcomes include cognitive performance measured by the Montreal Cognitive Assessment (MoCA) and serum T-Tau levels, assessed at baseline and after the 6-month intervention. Key secondary outcomes encompass changes in liver fibrosis (via FibroScan and FIB-4 index), inflammatory biomarkers (IL-6, TNF-α), and hormonal profiles (cortisol, testosterone, estradiol). The protocol has received ethical approval from the Khyber Medical University Institutional Review Board, and analysis will follow intention-to-treat principles using repeated-measures ANOVA and regression models to determine intervention efficacy and pathophysiological correlations.

Interventions

• Behavioral Structured Mediterranean Diet
  A culturally adapted, structured dietary plan based on the Mediterranean diet principles, delivered through individual dietitian counseling, provision of weekly meal plans, and ongoing compliance support (food diaries, recalls, monthly check-ins).
• Behavioral Control / General Advice
  This intervention consists of providing standardized, non-structured verbal and written information on the principles of a balanced diet and the benefits of regular physical activity, as per routine clinical practice. It serves as the active comparator representing minimal intervention.

Primary outcome measures

• Composite of Heart Failure Hospitalization or Cardiovascular Death [Time frame: From randomization up to study completion (maximum follow-up of 30 months).]
• Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score [Time frame: Baseline, Month 12.]
• Change in N-terminal pro-brain natriuretic peptide (NT-proBNP) [Time frame: Baseline, Month 6.]
• All-cause Mortality [Time frame: From randomization up to study completion (maximum follow-up of 30 months).]

Eligibility criteria

Inclusion criteria

• Age 18 to 42 years.
• Diagnosed with fatty liver (NAFLD) via imaging (e.g., ultrasound).
• Liver fibrosis assessed and staged via FibroScan and the FIB-4 index.
• Literate (to consent and complete cognitive assessments/questionnaires).

Exclusion criteria

• History of alcohol intake >20g/day.
• Chronic viral hepatitis B or C.
• Major neuropsychiatric illnesses.
• Pregnancy or breastfeeding.
• Chronic illnesses including Diabetes Mellitus and thyroid dysfunction.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Pakistan · 2 centers

• Khyber Teaching Hospital — Peshawar
• Northwest General Hospital — Peshawar

Publications

• Kjaergaard K, Mikkelsen ACD, Wernberg CW, Gronkjaer LL, Eriksen PL, Damholdt MF, Mookerjee RP, Vilstrup H, Lauridsen MM, Thomsen KL. Cognitive Dysfunction in Non-Alcoholic Fatty Liver Disease-Current Knowledge, Mechanisms and Perspectives. J Clin Med. 2021 Feb 9;10(4):673. doi: 10.3390/jcm10040673. PMID 33572481
• Semmler G, Datz C, Reiberger T, Trauner M. Diet and exercise in NAFLD/NASH: Beyond the obvious. Liver Int. 2021 Oct;41(10):2249-2268. doi: 10.1111/liv.15024. Epub 2021 Aug 21. PMID 34328248
• Whitehead AL, Julious SA, Cooper CL, Campbell MJ. Estimating the sample size for a pilot randomised trial to minimise the overall trial sample size for the external pilot and main trial for a continuous outcome variable. Stat Methods Med Res. 2016 Jun;25(3):1057-73. doi: 10.1177/0962280215588241. Epub 2015 Jun 19. PMID 26092476
• Ishiba H, Sumida Y, Tanaka S, Yoneda M, Hyogo H, Ono M, Fujii H, Eguchi Y, Suzuki Y, Yoneda M, Takahashi H, Nakahara T, Seko Y, Mori K, Kanemasa K, Shimada K, Imai S, Imajo K, Kawaguchi T, Nakajima A, Chayama K, Saibara T, Shima T, Fujimoto K, Okanoue T, Itoh Y; Japan Study Group of Non-Alcoholic Fatty Liver Disease (JSG-NAFLD). The novel cutoff points for the FIB4 index categorized by age increas PMID 29744597

Identifiers

NCT: NCT07294963 · KMU/DIR/CTU/2025/010

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗