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

August 4, 2023 updated by: Milena Schoenke, Leiden University Medical Center

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

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Netherlands
    • South Holland
      • Leiden, South Holland, Netherlands, 2333 ZA
        • Leiden University Medical Center
        • Contact:
        • Contact:
        • Principal Investigator:
          • Milena Schönke, PhD
        • Sub-Investigator:
          • Maarten E Tushuizen, MD PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Morning exercise
Individuals will exercise train at 8 AM three times per week for 12 weeks.
Behavioral: Exercise training
Mixed exercise training containing strength and endurance elements carried out under supervision
Experimental: Evening exercise
Individuals will exercise train at 8 PM three times per week for 12 weeks.
Behavioral: Exercise training
Mixed exercise training containing strength and endurance elements carried out under supervision

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Liver fat content
Time Frame: 12 weeks
Liver fat content (in %) will be measured by MRI LiverMultiScan
12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hepatic fibrosis
Time Frame: 12 weeks
Hepatic stiffness (in kPa) will be measured as a proxy for liver fibrosis by Fibroscan (transient elastography)
12 weeks
Body mass index (BMI)
Time Frame: 12 weeks
Body weight (in kg) and height (in m) will be combined to report BMI in kg/m^2
12 weeks
Fecal microbiota
Time Frame: 12 weeks
Fecal microbiota composition assessed via microbial sequencing
12 weeks
Cardiorespiratory fitness
Time Frame: 12 weeks
Peak workload (Wpeak) will be assessed with a the Steep Ramp Test (SRT) on a cycle ergometer
12 weeks
Waist circumference
Time Frame: 12 weeks
Waist circumference (in cm) will be measured with a measuring tape
12 weeks
Blood pressure
Time Frame: 12 weeks
Blood pressure (mmHg) will be measured using an arm cuff
12 weeks
Plasma levels of liver enzymes
Time Frame: 12 weeks
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
Plasma insulin levels
Time Frame: 12 weeks
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
Plasma glucose levels
Time Frame: 12 weeks
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
Blood lipid levels
Time Frame: 12 weeks
Blood triglyceride, LDL-cholesterol and HDL-cholesterol levels (all in mmol/L) will be quantified in the laboratory
12 weeks
Physical activity
Time Frame: 12 weeks
Self-reported physical activity (minutes of moderate-intensity activity per week) will be assessed with the International Physical Activity Questionnaire (IPAQ)
12 weeks
Sleep
Time Frame: 12 weeks
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
Food intake
Time Frame: 12 weeks
Self-reported food intake (type of food, quantity, time of intake) will be assessed with 3-day food diaries
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Leiden University Medical Center

Collaborators

Maag Lever Darm Stichting

Investigators

  • Principal Investigator: Milena Schönke, PhD, Leiden University Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

September 1, 2023

Primary Completion (Estimated)

September 1, 2024

Study Completion (Estimated)

September 1, 2024

Study Registration Dates

First Submitted

July 28, 2023

First Submitted That Met QC Criteria

August 4, 2023

First Posted (Actual)

August 14, 2023

Study Record Updates

Last Update Posted (Actual)

August 14, 2023

Last Update Submitted That Met QC Criteria

August 4, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NL83431.058.22

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

All IPD that underlie results in a publication

IPD Sharing Time Frame

Starting at publication

IPD Sharing Access Criteria

IPD that underlie results in a publication will be made available upon reasonable request

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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