Non-Alcoholic Fatty Liver DiseaseNCT07294963
Impact of Lifestyle Interventions on Cognitive Decline in Non-alcoholic Fatty Liver Disease
A study testing Structured Mediterranean Diet in people with Non-Alcoholic Fatty Liver Disease and Neurocognitive Disorders, run by Khyber Medical University Peshawar at 2 sites in Pakistan.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 42 years
- Conditions the study is for
- Non-Alcoholic Fatty Liver Disease, Neurocognitive Disorders
- What is being tested?
- Structured Mediterranean Diet
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 2 sitesPakistan
- Study dates
- 1 Oct 2025to 15 Jun 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 42 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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).
Who cannot join
- 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.
Trial locations and contacts
2 sites in 1 country.
Pakistan2 sites
Khyber Teaching Hospital
Peshawar, KPK, 25100
Northwest General Hospital
Peshawar, KPK, 25100
About this study
Official title: Impact of Lifestyle Interventions on Cognitive Decline in NAFLD: A Randomized Controlled Trial of Liver Fibrosis, Hormonal Imbalance, and Inflammatory Markers
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.
Read the 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.
- Being tested
- Structured Mediterranean Diet, Control / General Advice
- Keywords
- Hepatocerebral Syndrome, Metabolic dysfunction-Associated SteatoHepatitis, Cognitive Decline, Liver Fibrosis, Non-Alcoholic Fatty Liver Disease
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Neurocognitive Disorders, Cognitive Dysfunction, Liver Cirrhosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Structured Mediterranean DietBehavioural
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 AdviceBehavioural
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.
| Study group | Role | What they receive |
|---|---|---|
| Mediterranean Diet Intervention | Experimental | 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). Receives: Behavioral: Structured Mediterranean Diet |
| Control / General Advice | Active comparator | 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). Receives: Behavioral: Control / General Advice |
| Combined Diet and Exercise Intervention | Experimental | 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). Receives: Behavioral: Structured Mediterranean Diet; Behavioral: Control / General Advice |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite of Heart Failure Hospitalization or Cardiovascular Death
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).
Measured: From randomization up to study completion (maximum follow-up of 30 months).
Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score
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.
Measured: Baseline, Month 12.
Change in N-terminal pro-brain natriuretic peptide (NT-proBNP)
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.
Measured: Baseline, Month 6.
All-cause Mortality
Time from randomization to death from any cause.
Measured: From randomization up to study completion (maximum follow-up of 30 months).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2025
- Study start1 Oct 2025
- Primary completion28 Apr 2026
- Study completion15 Jun 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Non-Alcoholic Fatty Liver DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Khyber Medical University Peshawar
- Sponsor type
- University, hospital or other
- Collaborators
- Northwest General Hospital and Research centre, Khyber Teaching Hospital
- Responsible party
- Sponsor
- Investigators
- Dr Ayesha Qaiser, PhD Scholar, Principal investigator, Khyber Medical University PeshawarDr Inayat Shah, PhD, Principal investigator, Institute of Basic Medical Sciences, Khyber Medical UniversityDr Arshad Hussain, PhD, Principal investigator, Northwest General Hospital, Peshawar
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07294963
- Sponsor's protocol ID
- KMU/DIR/CTU/2025/010
- Status last verified
- Aug 2026
- First submitted
- 8 Dec 2025
- Last updated
- 18 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data that underlie the results reported in the primary publication (including demographic, clinical, laboratory, and cognitive assessment data) will be made available to qualified researchers upon reasonable request. The data will be shared to achieve the aims in the approved proposal, subject to a data use agreement.
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.
PubMed 33572481Semmler 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.
PubMed 34328248Whitehead 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.
PubMed 26092476Ishiba 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.
PubMed 29744597
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Lifestyle Interventions on Cognitive Decline in NAFLD: A Randomized Controlled Trial of Liver Fibrosis, Hormonal Imbalance, and Inflammatory Markers
- ClinicalTrials.gov ID
- NCT07294963
- Acronym / sponsor ID
- KMU/DIR/CTU/2025/010
- Keywords
- Hepatocerebral Syndrome, Metabolic dysfunction-Associated SteatoHepatitis, Cognitive Decline, Liver Fibrosis, Non-Alcoholic Fatty Liver Disease
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Khyber Medical University PeshawarUniversity, hospital or other
- Collaborators
- Northwest General Hospital and Research centre, Khyber Teaching Hospital
- Study start
- 1 Oct 2025 (actual)
- Primary completion
- 28 Apr 2026 (actual)
- Study completion
- 15 Jun 2026 (actual)
- First posted
- 19 Dec 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 3
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Mediterranean Diet Intervention | Experimental | Behavioral: Structured Mediterranean DietParticipants 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). |
| Control / General Advice | Active comparator | Behavioral: Control / General AdviceParticipants 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). |
| Combined Diet and Exercise Intervention | Experimental | Behavioral: Structured Mediterranean Diet, Behavioral: Control / General AdviceParticipants 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). |
Who may qualify
- Ages
- 18 to 42 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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).
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Structured Mediterranean DietA 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). | Behavioural | Combined Diet and Exercise Intervention, Mediterranean Diet Intervention |
| Control / General AdviceThis 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. | Behavioural | Combined Diet and Exercise Intervention, Control / General Advice |
Primary outcome
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2026.
- Background: PubMed 33572481Kjaergaard 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.
- Background: PubMed 34328248Semmler 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.
- Background: PubMed 26092476Whitehead 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.
- Background: PubMed 29744597Ishiba 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.
- Individual participant dataSharing planned: Yes. De-identified individual participant data that underlie the results reported in the primary publication (including demographic, clinical, laboratory, and cognitive assessment data) will be made available to qualified researchers upon reasonable request. The data will be shared to achieve the aims in the approved proposal, subject to a data use agreement.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dr Ayesha Qaiser, PhD Scholar principal investigator
Khyber Medical University Peshawar
Dr Inayat Shah, PhD principal investigator
Institute of Basic Medical Sciences, Khyber Medical University
Dr Arshad Hussain, PhD principal investigator
Northwest General Hospital, Peshawar
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Structured Mediterranean Diet in people with Non-Alcoholic Fatty Liver Disease and Neurocognitive Disorders, run by Khyber Medical University Peshawar at 2 sites in Pakistan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Pakistan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Composite of Heart Failure Hospitalization or Cardiovascular Death (time frame: From randomization up to study completion (maximum follow-up of 30 months).). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07294963, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Aug 2026.