The Clock Thickens: Morning or Evening Training for the Treatment of NAFLD?

Non-Alcoholic Fatty Liver Disease Clinical Trial

— TikTac  

Official title:

The Clock Thickens: Morning or Evening Training for the Treatment of NAFLD? (TikTac Study)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05987748
• Other study ID #: NL83431.058.22
• Status: Not yet recruiting
• Phase: N/A
• Start date: September 1, 2023
• Est. completion date: September 1, 2024

Study information

• Verified date: August 2023
• Source: Leiden University Medical Center
• Contact: Milena Schönke, PhD
• Phone: +31715268188
• Email: m.schoenke[@]lumc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this clinical trial is to investigate the different effect of morning and evening exercise training in individuals with non-alcoholic fatty liver disease (NAFLD). The main question it aims to answer is: • Is morning or evening exercise better for the treatment of NAFLD? Participants will follow a supervised exercise training program for three months with either morning or evening training and the effect on liver health will be assessed. Researchers will compare the morning to the evening exercise group to see if one training timepoint is more effective than the other in reducing the amount of fat in the liver and improving liver health.

Description:

The aim of the study is to identify the effect of exercise timing on NAFLD. Additionally, we aim to increase the understanding of the exercise-related modulation of the metabolic and inflammatory processes causing NAFLD, including insulin resistance and dysbiosis of the gut microbiota. Forty obese patients with NAFLD will be enrolled by randomization to participate in an exercise training program over 12 weeks, either in the morning (n=20) or evening (n=20). Blood and stool samples will be collected before, during and after the intervention to monitor diagnostic markers such as liver enzymes (AST, ALT, GGT, etc.) and changes of the gut microbiota with exercise, respectively. Moreover, mixed meal tolerance tests will be performed before and after the intervention to monitor insulin sensitivity and hepatic fat content and cardiovascular parameters (e.g. arterial stiffness) will be monitored via MRI. Throughout the study, physical fitness will be assessed and monitored using steep ramp tests. Patients will be randomized for a supervised, standardized 50 min morning or evening training, with both progressive endurance and strength elements, in a frequency of 3 times a week for 12 weeks.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: September 1, 2024
• Est. primary completion date: September 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years to 75 Years

Eligibility

Inclusion Criteria:

• Age = 45 years and = 75
• Obese (BMI > 27 kg/m2)
• Males and postmenopausal females
• Caucasian
• Hepatic steatosis defined as increased hyperechogenicity of the liver on abdominal ultrasound, CAP score on Fibroscan > 280, and/or histological signs of steatosis
• Sedentary lifestyle (maximum of 20 minutes of moderate-to-vigorous physical activity per day on less than three days per week)
• Written informed consent

Exclusion Criteria:

• Exclusion criteria for MRI (claustrophobia, pacemaker, metal implants, etc.)
• Any other liver disease than NAFLD/NASH
• Present excessive alcohol use defined as > 2 units/day
• Recent use (< 3 months) of antibiotics
• Recent changes in dosages of regular medication (< 3 months)
• Recent (< 3 months) weight change (>5%)
• Recent (< 3 months) substantial diet changes
• Cardiovascular co-morbidity defined as heart failure, coronary insufficiency and hypertension in past history
• Comorbidity that contraindicates exercise training and exercise testing or that affects exercise response and exercise capacity
• Ongoing or recent use of glucocorticoids, oral/transdermal hormonal substitution, paclitaxel, theofyllin, amiodarone, myelosuppresive agents
• A psychiatric, addictive or any other disorder that compromises the subjects ability to understand the study content and to give written informed consent for participation in the study
• Working night or alternating shifts, known sleeping disorders such as narcolepsy or insomnia

Related Conditions & MeSH terms

• Fatty Liver
• Liver Diseases
• Non-Alcoholic Fatty Liver Disease

Intervention

Behavioral:
• Exercise training
Mixed exercise training containing strength and endurance elements carried out under supervision

Locations

Country	Name	City	State
Netherlands	Leiden University Medical Center	Leiden	South Holland

Sponsors (2)

Lead Sponsor	Collaborator
Leiden University Medical Center	Maag Lever Darm Stichting

Country where clinical trial is conducted

Netherlands, 

References & Publications (29)

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* Note: There are 29 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Liver fat content	Liver fat content (in %) will be measured by MRI LiverMultiScan	12 weeks
Secondary	Hepatic fibrosis	Hepatic stiffness (in kPa) will be measured as a proxy for liver fibrosis by Fibroscan (transient elastography)	12 weeks
Secondary	Body mass index (BMI)	Body weight (in kg) and height (in m) will be combined to report BMI in kg/m^2	12 weeks
Secondary	Fecal microbiota	Fecal microbiota composition assessed via microbial sequencing	12 weeks
Secondary	Cardiorespiratory fitness	Peak workload (Wpeak) will be assessed with a the Steep Ramp Test (SRT) on a cycle ergometer	12 weeks
Secondary	Waist circumference	Waist circumference (in cm) will be measured with a measuring tape	12 weeks
Secondary	Blood pressure	Blood pressure (mmHg) will be measured using an arm cuff	12 weeks
Secondary	Plasma levels of liver enzymes	Plasma levels of aspartate transaminase (ASAT), alanine aminotransferase (ALAT), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP) (all in units/L) and bilirubin (in umol/L) will be quantified in the laboratory	12 weeks
Secondary	Plasma insulin levels	Plasma insulin (in pmol/L) will be measured during a mixed meal test after 0, 10, 20, 30, 40, 60, 90, 120 and 180 minutes of the ingestion of a mixed meal	12 weeks
Secondary	Plasma glucose levels	Plasma glucose (in mmol/L) will be measured during a mixed meal test after 0, 10, 20, 30, 40, 60, 90, 120 and 180 minutes of the ingestion of a mixed meal	12 weeks
Secondary	Blood lipid levels	Blood triglyceride, LDL-cholesterol and HDL-cholesterol levels (all in mmol/L) will be quantified in the laboratory	12 weeks
Secondary	Physical activity	Self-reported physical activity (minutes of moderate-intensity activity per week) will be assessed with the International Physical Activity Questionnaire (IPAQ)	12 weeks
Secondary	Sleep	Sleeping habits (bedtime, time of falling asleep, time of waking up, sleep duration) will be assessed via the Munich Chronotype Questionnaire (MCTQs 5.0).	12 weeks
Secondary	Food intake	Self-reported food intake (type of food, quantity, time of intake) will be assessed with 3-day food diaries	12 weeks