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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Non-alcoholic Steatohepatitis, Non-alcoholic Fatty Liver Disease

Intervention / Treatment
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* Other: High-intensity Interval Training


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 59 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High-intensity Interval Training (HIT)<br>6 week control period with no intervention then 6 weeks of twice weekly HIT | Other: High-intensity Interval Training<br>* 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.<br>* Other names: Exercise;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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High-intensity Interval Training