Exercise and Cerebral Hemodynamics in MAFLD.

NCT05520697 | Unknown

• 1 other identifier: GAS-3608-21-23-1
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

Arterial stiffness and endothelial dysfunction present in metabolic associated fatty liver disease (MAFLD) confer increased cardiovascular risk, which represents the leading cause of mortality in this group of patients. Mechanisms involved in the cardiovascular complications of MAFLD have recently been found to also affect cerebral blood flow altering cerebral hemodynamics in MAFLD subjects. These alerations can be detected through transcranial Doppler, which measures markers of cerebrovascular vasoconstriction, which indicates cerebrovascular autoregulation.16 These abnormalities are related to vascular disease in MAFLD, which plays an essential role in ischemic stroke and cognitive impairment, which explains why MAFLD patients had lower scores on cognitive function tests.17 Nonetheless, there are no studies evaluating the effect of lifestyle interventions (specifically exercise) on cerebral hemodynamics in patients with MAFLD, however, it has been shown that in other pathologies that share pathophysiological similarities with NAFLD there are beneficial changes in this outcome. An example of the above is chronic heart failure and liver cirrhosis, where physical exercise attenuates the inflammatory cascade (decrease in IL6, IL8, IL12, TNFa), and decreases the activation of the renin-angiotensin system with a direct effect on endothelial function improvement. Our research group also documented that a 12-week physical training program acts on this mechanism and has a beneficial effect on cerebral hemodynamics evaluated by transcranial Doppler in patients with liver cirrhosis, which leads to an improvement in neuropsychometric tests.18 Improvement in the previously described pathways through a 16-week physical training program in MAFLD patients could potentially improve alterations in cerebral blood flow, cognitive function, endothelial function, body composition, and the degree of liver steatosis and fibrosis. This outcome has never been assessed in MAFLD patients undergoing exercise. In addition, although there are studies that demonstrate the impact of diet and exercise, most have evaluated these interventions individually, which represents a limitation when implementing them as a multidisciplinary intervention. Therefore, our hypothesis is that a 16-week physical training program will improve cerebral hemodynamic parameters in patients with metabolic-associated fatty liver compared to a control group without a physical training program.

Conditions

Non-alcoholic Fatty Liver Disease

Outcome Measures

Primary Outcomes (2)

• Chage in Pulsatility index (PI) of the middle cerebral artery

  The pulsatility index (PI) of the middle cerebral artery is a calculated parameter in doppler ultrasound, derived from the maximum, minimum, and mean Doppler frequency shifts during a defined cardiac cycle. Along with resistive index (RI), it is typically used to assess the resistance in a pulsatile vascular system.

  The first measurement occurs at the baseline visit and the last measurement at the sixteenth week for a total of 18 weeks between the first and last measurement.

• Change in Resistance index (RI) of the middle cerebral artery

  RI is a calculated flow parameter in doppler ultrasound of the of the middle cerebral artery, derived from the maximum, minimum, and mean Doppler frequency shifts during a defined cardiac cycle. Along with the pulsatility index (PI), it is typically used to assess the resistance in a pulsatile vascular system.

  The first measurement occurs at the baseline visit and the last measurement at the sixteenth week for a total of 18 weeks between the first and last measurement.

Secondary Outcomes (9)

• Change in Liver steatosis

  The first measurement occurs at the baseline visit and the last measurement at the sixteenth week for a total of 18 weeks between the first and last measurement.

• Change in Liver fibrosis

  The first measurement occurs at the baseline visit and the last measurement at the sixteenth week for a total of 18 weeks between the first and last measurement.

• Change in BMI (kg/m^2)

  The first measurement is at the baseline visit, then at week 1, week 4, week 8, week 12, and week 16, for a total of 18 weeks between the first and last measurement

• Change in Endothelial function

  The first measurement occurs at the baseline visit and the last measurement at the sixteenth week for a total of 18 weeks between the first and last measurement.

• Change in Cognitive evaluation

  The first measurement occurs at the baseline visit and the last measurement at the sixteenth week for a total of 18 weeks between the first and last measurement.

Other Outcomes (3)

• Change in Resting energy expenditure (REE)

  Only at the baseline visit (week 1)

• Change in number of steps/day

  The first measurement is made two weeks before initiating the trial, then at week 1, week 4, week 8, week 12, and week 16, for a total of 18 weeks between the first and last measurement.

• change in microbiota diversity.

  The first measurement is made two weeks before initiating the trial and at week 16, for a total of 18 weeks between the first and last measurement

Study Arms (2)

Control

ACTIVE COMPARATOR

Nutritional treatment with caloric restriction and mental exercise

Behavioral: Nutritional intervention; Behavioral: Mental exercise.

Intervention

EXPERIMENTAL

Nutritional treatment with caloric restriction, mental exercise, and physical training program.

Behavioral: Nutritional intervention; Behavioral: Mental exercise.; Behavioral: Physical training.

Interventions

Nutritional intervention BEHAVIORAL

Nutritional treatment with caloric restriction.

Control; Intervention

Mental exercise. BEHAVIORAL

Mental exercise.

Control; Intervention

Physical training. BEHAVIORAL

Exercise.

Intervention

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients with a diagnosis of MAFLD (biopsy and/or imaging and clinical context).
• Both sexes.
• Age 18-60 years.
• BMI \>30Kg/m2.
• Not having participated in another intervention protocol for MAFLD in the previous three months.
• Patients who agree to participate and sign the informed consent.

You may not qualify if:

• Heart failure.
• Uncontrolled DM2, diabetic complications, known peripheral vascular disease, or neuropathy.
• Cancer.
• Orthopedic inability to exercise.
• With advanced liver fibrosis (\>F2), estimated by transient elastography.
• Loss of \>10% of their body weight in the last three months.
• Consumption of supplements/food supplements and/or current or previous significant consumption of alcohol for more than three previous consecutive months (\>30 g in women and \>40 g in men).
• Patients with neurological disorders.

Sponsors & Collaborators

• Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran: lead

Study Sites (1)

Instituto nacional de ciencias Médicas y Nutrición Salvador Zubirán

Mexico City, 14080, Mexico

RECRUITING

Related Publications (1)

• Roman-Calleja BM, Ruiz-Margain A, Duarte-Rojo A, Flores-Silva F, Martinez-Cabrera CF, Gutierrez-Rosas LE, Valencia-Pena BA, Cantu-Brito C, Chalasani N, Aguilar-Salinas CA, Macias-Rodriguez RU. Physical exercise improves neurocognition in patients with metabolic dysfunction-associated steatotic liver disease. Liver Transpl. 2025 Nov 3. doi: 10.1097/LVT.0000000000000767. Online ahead of print.

  PMID: 41182078 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

Physical Conditioning, Human

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Exercise; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Ricardo Macías-Rodríguez, MD,MSc,PhD

  Department of Gastroenterology, INCMNSZ

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ricardo Macías-Rodríguez, MD,MSc,PhD

CONTACT

+525554870900; ricardomacro@yahoo.com.mx

Berenice Román-Calleja, BSc, MSc

CONTACT

+525554870900; berermn@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor Hepatology/Clinical Researcher

Model Details: Intervention

Study Record Dates

• First Submitted: August 23, 2022
• First Posted: August 30, 2022
• Study Start: December 1, 2020
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2024
• Last Updated: August 30, 2022

Record last verified: 2022-08

Locations

ME (1)