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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Поведенческое 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).
• Поведенческое 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.

Первичные конечные точки

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

Критерии участия

Критерии включения

• 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).

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Пакистан · 2 центра

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

Публикации

• 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

Идентификаторы

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

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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