The Effect of HIT in Patients With Non-alcoholic Fatty Liver Disease/Steatohepatitis

A Pilot Project to Assess the Effect of High-intensity Interval Training in Patients With Non-alcoholic Fatty Liver Disease/Steatohepatitis

This pilot study aims to investigate whether 6 weeks of twice weekly High-intensity Interval Training (HIT) results in improvements in disease-specific measures, feelings of general well-being, physical fitness and cognitive function in patients with non-alcoholic fatty liver disease or non-alcoholic steatohepatitis.

Study Overview

• Status: Completed
• Conditions: Non-alcoholic Fatty Liver Disease; Non-alcoholic Steatohepatitis
• Intervention / Treatment: Other: High-intensity Interval Training

Detailed Description

The study aims to recruit up to 12 patients diagnosed with non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) from the liver clinics at Ninewells Hospital, Dundee. Suitable patients who give informed consent will be assessed at baseline, again after 6 weeks of no intervention to act as a control period, and thirdly after 6 weeks of twice-weekly high-intensity interval training (HIT).

Assessments will be performed with the patient fasted overnight, and will involve body composition measurements, blood pressure, a venous blood sample for circulating triglycerides, fasting glucose, insulin, liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and platelets. An oral glucose tolerance test will be performed using fingerprick capillary samples. Cognitive function tests for episodic memory, executive function and semantic memory will be performed and a questionnaire (SF-36) will be used to assess general well-being. Physical fitness will be assessed through a 12-minute walk test on a treadmill, which will allow estimation of maximal oxygen uptake capacity (VO2 max), and a "get up and go" test will be used to assess physical function.

The exercise intervention will involve a 2 minute warm-up, cycling at 50 rpm before the participants will be asked to cycle at 100rpm and a weight will be added (7% body weight for men and 6% body weight for women) as resistance. The sprint will last 6 seconds and the participant will be asked to rest for at least 1 minute. This will be repeated for a total of 5 sprints in sessions 1-3, 6 sprints in session 4, 7 sprints in sessions 5&6, 8 sprints in sessions 7&8, 9 sprints in sessions 9&10 and 10 sprints in sessions 11&12. Exercise heart rate will be monitored and recorded.

At least 3 days after the last HIT session the pre-intervention testing assessment will be repeated for a third time.

Changes in measured variables will be analysed via repeated measures analysis of variance (ANOVA) with post-hoc testing of all variables.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Dundee, United Kingdom, DD1 9SY
    • Ninewells Hospital
  • Dundee, United Kingdom, DD1 1HG
    • Abertay University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 59 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• clinical diagnosis of non-alcoholic fatty liver disease or non-alcoholic steatohepatitis
• attending a specialist liver clinic at Ninewells Hospital, Dundee

Exclusion Criteria:

• unstable cardiovascular disease
• uncontrolled arrhythmias
• structural cardiac abnormalities
• uncontrolled diabetes
• other uncontrolled metabolic abnormalities
• severe orthopaedic condition that would prohibit exercise
• severe pulmonary condition that would prohibit exercise
• any other poorly controlled medical condition.
• resting systolic blood pressure above 160 mm Hg
• resting diastolic blood pressure above 90 mm Hg
• symptomatic postural drop in blood pressure greater than 20 mm Hg

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: High-intensity Interval Training (HIT); 6 week control period with no intervention then 6 weeks of twice weekly HIT

Other: High-intensity Interval Training; 2 minute warm-up at 50rpm, then increase to 100rpm. Weight added to bike (7% body weight for men 6% body weight for women). Continue effort for 6 seconds, then passive rest for at least 1 minute. Total 5 sprints in sessions 1-3, 6 sprints in session4, 7 sprints in sessions 5&6, 8 sprints in sessions 7&8, 9 sprints in sessions 9&10 and 10 sprints in sessions 11&12.; Other Names: Exercise

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)	calculation of insulin resistance via formula: fasting insulin (mIU/L) x fasting glucose (mg/dL)/405 normal insulin resistance -HOMA score <3 moderate insulin resistance -HOMA score 3-5 severe insulin resistance -HOMA score >5 Assessed at baseline, after 6 week control period and within 1 week of completing 6 weeks HIT	Baseline, Follow up at 6 Weeks and following HIT intervention at 12 Weeks
Oral Glucose Tolerance Test	measurement of capillary samples for glucose at time 0, followed by every 20 minutes for 2 hours following ingestion of 75g glucose. Results graphed against time, then area under the curve calculated for each of the 3 assessments.	Baseline, Follow up at 6 Weeks and following HIT intervention at 12 Weeks
AST: ALT Ratio	ratio of liver enzymes aspartate aminotransferase (AST) to alanine aminotransferase (ALT). used as a diagnostic aid e.g. AST:ALT of more than 2:1 is characteristic of alcoholic liver disease whereas fatty steatosis and many other causes of liver disease, ratio is less than or equal to 1. Ratio may rise as fibrosis and cirrhosis develop in viral hepatitis.	Baseline, Follow up at 6 Weeks and following HIT intervention at 12 Weeks
FIB-4	calculated from AST, ALT, platelets and participant's age and used to estimate amount of fibrosis in liver. Fib-4 score of <1.45 has negative predictive value of 90% for advanced fibrosis.	Baseline, Follow up at 6 Weeks and following HIT intervention at 12 Weeks
Body Fat Mass Estimated Via Bioimpedance	total body fat and trunk fat estimated via bioimpedance measured after overnight fast, expressed as percentage	Baseline, Follow up at 6 Weeks and following HIT intervention at 12 Weeks
Blood Pressure	taken with participant supine, measured on left arm	Baseline, Follow up at 6 Weeks and following HIT intervention at 12 Weeks
General Well-being as Assessed by SF-36 Questionnaire	Assessment of: physical functioning, social functioning, mental health, pain, change in health, physical role limitation, mental role limitation, energy and vitality, health perception over preceding 4 weeks (other than change in health, which is a comparison to health the preceding year), expressed as a transformed score range 0-100, with a higher score indicating better function/freedom from pain etc	Baseline, Follow up at 6 Weeks and following HIT intervention at 12 Weeks
Short-term Memory Recall	testing of verbal word presentation-immediate recall of 10 words (60 seconds for recall) Maximum =10, minimum =0	Baseline, Follow up at 6 Weeks and following HIT intervention at 12 Weeks
Estimated VO2 Max	VO2 max estimated via submaximal exercise test-submaximal treadmill walking test Calculated via formula: VO2max= 15.1+21.8 x speed (miles per hour) - 0.327 x heart rate (beats per minute) - 0.263 x speed x age (years) + 0.00504 x heart rate x age + 5.98 x gender (0=female, 1=male)	Baseline, Follow up at 6 Weeks and following HIT intervention at 12 Weeks
Physical Function-"Get up and go" Test	participant will be timed standing up from chair unaided,walking 30m, turning round and returning to a seated position on the chair, the average time of 3 attempts will be recorded.	Baseline, Follow up at 6 Weeks and following HIT intervention at 12 Weeks
Ankle Brachial Pressure Index (ABPI)	ratio of blood pressure in left arm and right ankle	Baseline, Follow up at 6 Weeks and following HIT intervention at 12 Weeks
Long-term Memory Recall	testing of verbal word presentation-delayed recall of 10 words 10 minutes after words initially presented (within 60 seconds). Maximum= 10 words, minimum = no words	Baseline, Follow up at 6 Weeks and following HIT intervention at 12 Weeks
Executive Function (Verbal Fluency Test)	written verbal fluency test: participant asked to write down as many English words as possible within 60 seconds, starting with a particular letter of the alphabet, excluding proper nouns or plurals. Baseline assessment-letter A Post Control assessment -letter S After HIT assessment -letter F	Baseline, Follow up at 6 Weeks and following HIT intervention at 12 Weeks

Collaborators and Investigators

• Sponsor: University of Bath
• Collaborators: Abertay University
• Investigators: Principal Investigator: Niels BJ Vollaard, PhD, University of Bath

Study record dates

Study Major Dates

• Study Start: October 1, 2015
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): June 1, 2016

Study Registration Dates

• First Submitted: August 10, 2015
• First Submitted That Met QC Criteria: August 18, 2015
• First Posted (Estimate): August 19, 2015

Study Record Updates

• Last Update Posted (Actual): May 4, 2018
• Last Update Submitted That Met QC Criteria: May 3, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: High-intensity Interval Training
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: 2015CM

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: There is no reason to share the IPD.