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

NCT ID: NCT07294963

Last Updated: 2025-12-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

45 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-10-01

Study Completion Date

2026-06-15

Brief Summary

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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

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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.

Conditions

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Non-Alcoholic Fatty Liver Disease Neurocognitive Disorders

Keywords

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Hepatocerebral Syndrome Metabolic dysfunction-Associated SteatoHepatitis Cognitive Decline Liver Fibrosis Non-Alcoholic Fatty Liver Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

A three-arm parallel-group randomized controlled trial will be conducted. Participants will be assigned to the Mediterranean Diet intervention, Control (general advice 2), and combined Mediterranean Diet + Structured Exercise intervention.
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors
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.

Study Groups

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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).

Group Type EXPERIMENTAL

Structured Mediterranean Diet

Intervention Type BEHAVIORAL

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).

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).

Group Type ACTIVE_COMPARATOR

Control / General Advice

Intervention Type BEHAVIORAL

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.

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).

Group Type EXPERIMENTAL

Structured Mediterranean Diet

Intervention Type BEHAVIORAL

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).

Control / General Advice

Intervention Type BEHAVIORAL

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.

Interventions

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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).

Intervention Type 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.

Intervention Type BEHAVIORAL

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

42 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Northwest General Hospital and Research centre

NETWORK

Sponsor Role collaborator

Khyber Teaching Hospital

OTHER

Sponsor Role collaborator

Khyber Medical University Peshawar

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Dr Ayesha Qaiser, PhD Scholar

Role: PRINCIPAL_INVESTIGATOR

Khyber Medical University Peshawar

Dr Inayat Shah, PhD

Role: PRINCIPAL_INVESTIGATOR

Institute of Basic Medical Sciences, Khyber Medical University

Dr Arshad Hussain, PhD

Role: PRINCIPAL_INVESTIGATOR

Northwest General Hospital, Peshawar

Locations

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Khyber Teaching Hospital

Peshawar, KPK, Pakistan

Site Status RECRUITING

Northwest General Hospital

Peshawar, KPK, Pakistan

Site Status RECRUITING

Countries

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Pakistan

Central Contacts

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Dr Ayesha Qaiser, MBBS, PhD Scholar

Role: CONTACT

Phone: +92 332 9135697

Email: [email protected]

Dr Inayat Shah, PhD

Role: CONTACT

Phone: +92 332 1431414

Email: [email protected]

Facility Contacts

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Dr Ayesha Qaiser, PhD Scholar

Role: primary

Dr Arshad Hussain, PhD

Role: backup

Dr Ayesha Qaiser, PhD Scholar

Role: primary

Dr Inayat Shah, PhD

Role: backup

References

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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.

Reference Type BACKGROUND
PMID: 33572481 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 34328248 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26092476 (View on PubMed)

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 increase the diagnostic accuracy in NAFLD: a multi-center study. J Gastroenterol. 2018 Nov;53(11):1216-1224. doi: 10.1007/s00535-018-1474-y. Epub 2018 May 9.

Reference Type BACKGROUND
PMID: 29744597 (View on PubMed)

Other Identifiers

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KMU/DIR/CTU/2025/010

Identifier Type: -

Identifier Source: org_study_id