Impact of Lifestyle Interventions on Cognitive Decline in NAFLD: A Randomized Controlled Trial of Liver Fibrosis, Hormonal Imbalance, and Inflammatory Markers
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Enrollment
- 45
- Locations
- 4
- Primary Endpoint
- Composite of Heart Failure Hospitalization or Cardiovascular Death
Study Overview
Brief Summary
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Single (Outcomes Assessor)
Masking Description
Outcome assessors conducting the Montreal Cognitive Assessment (MoCA) and laboratory technicians performing biomarker analyses (ELISA for T-Tau, cytokines, hormones) will be blinded to group assignment. Participants and the interventionists (dietitians, physiotherapists) cannot be blinded due to the behavioral nature of the lifestyle interventions.
Eligibility Criteria
- Ages
- 18 Years to 42 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Arms & Interventions
Mediterranean Diet Intervention
Participants will follow a structured, culturally adapted Mediterranean diet plan for 6 months, designed and supervised by a qualified dietitian. The diet emphasizes whole grains, vegetables, fruits, legumes, nuts, olive oil, and lean proteins (detailed 7-day plan in Annexure 7). Support includes individualized counseling, provision of meal plans, weekly food diaries, 24-hour dietary recalls, and monthly check-ins. Outcome assessments occur at T0, T1 (6 months), and T2 (12 months).
Intervention: Structured Mediterranean Diet (Behavioral)
Control / General Advice
Participants will receive general verbal and written advice on healthy eating and physical activity, consistent with standard care. No structured diet plan or supervised exercise will be provided. They will undergo all outcome assessments (FibroScan, FIB-4, MoCA, biomarker blood draws) at Baseline (T0), 6 months (T1), and 12 months (T2).
Intervention: Control / General Advice (Behavioral)
Combined Diet and Exercise Intervention
Participants will receive the identical Mediterranean diet intervention as Arm 2 plus a structured, progressive aerobic exercise program. The exercise consists of a 60-minute walking session, 5 days per week, for 6 months, progressing through conditioning, strength-building, and endurance phases (detailed in Annexure III). Compliance is monitored via exercise logs, fortnightly contact, and monthly check-ins. Outcome assessments occur at T0, T1 (6 months), and T2 (12 months).
Intervention: Structured Mediterranean Diet (Behavioral)
Combined Diet and Exercise Intervention
Participants will receive the identical Mediterranean diet intervention as Arm 2 plus a structured, progressive aerobic exercise program. The exercise consists of a 60-minute walking session, 5 days per week, for 6 months, progressing through conditioning, strength-building, and endurance phases (detailed in Annexure III). Compliance is monitored via exercise logs, fortnightly contact, and monthly check-ins. Outcome assessments occur at T0, T1 (6 months), and T2 (12 months).
Intervention: Control / General Advice (Behavioral)
Outcomes
Primary Outcomes
Composite of Heart Failure Hospitalization or Cardiovascular Death
Time Frame: From randomization up to study completion (maximum follow-up of 30 months).
Time to first adjudicated event of either hospitalization for worsening heart failure or cardiovascular death. Events will be confirmed by a blinded Clinical Events Committee (CEC).
Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score
Time Frame: Baseline, Month 12.
The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a 23-item, self-administered disease-specific questionnaire. The Overall Summary Score (OSS) aggregates the physical limitation, symptom frequency, quality of life, and social limitation domains. Scores range from 0 to 100, where higher scores indicate better health status. The outcome is the change in KCCQ-OSS from baseline.
Change in N-terminal pro-brain natriuretic peptide (NT-proBNP)
Time Frame: Baseline, Month 6.
The ratio of change in serum NT-proBNP level from baseline. NT-proBNP will be measured in pg/mL by a central laboratory using a standardized assay.
All-cause Mortality
Time Frame: From randomization up to study completion (maximum follow-up of 30 months).
Time from randomization to death from any cause.
Secondary Outcomes
No secondary outcomes reported