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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

Status
Completed
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT02528305
Enrollment
12
Registered
2015-08-19
Start date
2015-10-31
Completion date
2016-06-30
Last updated
2018-05-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Non-alcoholic Fatty Liver Disease, Non-alcoholic Steatohepatitis

Keywords

High-intensity Interval Training

Brief summary

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

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.

Interventions

OTHERHigh-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.

Sponsors

Abertay University
CollaboratorOTHER
University of Bath
Lead SponsorOTHER

Study design

Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE

Masking description

No Masking, this was not possible with this study design.

Eligibility

Sex/Gender
ALL
Age
20 Years to 59 Years
Healthy volunteers
No

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

Design outcomes

Primary

MeasureTime frameDescription
Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)Baseline, Follow up at 6 Weeks and following HIT intervention at 12 Weekscalculation 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
Oral Glucose Tolerance TestBaseline, Follow up at 6 Weeks and following HIT intervention at 12 Weeksmeasurement 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.
AST: ALT RatioBaseline, Follow up at 6 Weeks and following HIT intervention at 12 Weeksratio 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.
FIB-4Baseline, Follow up at 6 Weeks and following HIT intervention at 12 Weekscalculated 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.
Body Fat Mass Estimated Via BioimpedanceBaseline, Follow up at 6 Weeks and following HIT intervention at 12 Weekstotal body fat and trunk fat estimated via bioimpedance measured after overnight fast, expressed as percentage
Blood PressureBaseline, Follow up at 6 Weeks and following HIT intervention at 12 Weekstaken with participant supine, measured on left arm
General Well-being as Assessed by SF-36 QuestionnaireBaseline, Follow up at 6 Weeks and following HIT intervention at 12 WeeksAssessment 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
Short-term Memory RecallBaseline, Follow up at 6 Weeks and following HIT intervention at 12 Weekstesting of verbal word presentation-immediate recall of 10 words (60 seconds for recall) Maximum =10, minimum =0
Estimated VO2 MaxBaseline, Follow up at 6 Weeks and following HIT intervention at 12 WeeksVO2 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)
Physical Function-Get up and go TestBaseline, Follow up at 6 Weeks and following HIT intervention at 12 Weeksparticipant 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.
Ankle Brachial Pressure Index (ABPI)Baseline, Follow up at 6 Weeks and following HIT intervention at 12 Weeksratio of blood pressure in left arm and right ankle
Long-term Memory RecallBaseline, Follow up at 6 Weeks and following HIT intervention at 12 Weekstesting of verbal word presentation-delayed recall of 10 words 10 minutes after words initially presented (within 60 seconds). Maximum= 10 words, minimum = no words
Executive Function (Verbal Fluency Test)Baseline, Follow up at 6 Weeks and following HIT intervention at 12 Weekswritten 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

Countries

United Kingdom

Participant flow

Participants by arm

ArmCount
High-intensity Interval Training (HIT)
6 week control period with no intervention then 6 weeks of twice weekly HIT 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.
12
Total12

Withdrawals & dropouts

PeriodReasonFG000
Overall StudyAdverse Event1
Overall StudyPhysician Decision1
Overall StudyWithdrawal by Subject1

Baseline characteristics

CharacteristicHigh-intensity Interval Training (HIT)
Age, Categorical
<=18 years
0 Participants
Age, Categorical
>=65 years
0 Participants
Age, Categorical
Between 18 and 65 years
12 Participants
Age, Continuous45 years
STANDARD_DEVIATION 8
body mass index (BMI)29.6 kg/m^2
STANDARD_DEVIATION 3.8
diagnosis
Non-alcoholic Fatty Liver Disease (NAFLD)
7 participants
diagnosis
Non-alcoholic Steatohepatitis (NASH)
5 participants
height1.71 metres
STANDARD_DEVIATION 0.09
Sex: Female, Male
Female
2 Participants
Sex: Female, Male
Male
10 Participants

Adverse events

Event typeEG000
affected / at risk
deaths
Total, all-cause mortality
— / —
other
Total, other adverse events
0 / 12
serious
Total, serious adverse events
1 / 12

Outcome results

Primary

Ankle Brachial Pressure Index (ABPI)

ratio of blood pressure in left arm and right ankle

Time frame: Baseline, Follow up at 6 Weeks and following HIT intervention at 12 Weeks

ArmMeasureValue (MEAN)Dispersion
Baseline AssessmentAnkle Brachial Pressure Index (ABPI)1.15 ABPIStandard Deviation 0.16
After 6 Week Control PeriodAnkle Brachial Pressure Index (ABPI)1.08 ABPIStandard Deviation 0.18
After HIT AssessmentAnkle Brachial Pressure Index (ABPI)1.13 ABPIStandard Deviation 0.27
p-value: 0.793ANOVA
Primary

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.

Time frame: Baseline, Follow up at 6 Weeks and following HIT intervention at 12 Weeks

ArmMeasureValue (MEAN)Dispersion
Baseline AssessmentAST: ALT Ratio0.5 ratioStandard Deviation 0.2
After 6 Week Control PeriodAST: ALT Ratio0.5 ratioStandard Deviation 0.2
After HIT AssessmentAST: ALT Ratio0.5 ratioStandard Deviation 0.2
p-value: 0.303ANOVA
Primary

Blood Pressure

taken with participant supine, measured on left arm

Time frame: Baseline, Follow up at 6 Weeks and following HIT intervention at 12 Weeks

ArmMeasureGroupValue (MEAN)Dispersion
Baseline AssessmentBlood Pressurediastolic blood pressure85 mmHgStandard Deviation 13
Baseline AssessmentBlood Pressuresystolic blood pressure139 mmHgStandard Deviation 18
After 6 Week Control PeriodBlood Pressuresystolic blood pressure142 mmHgStandard Deviation 13
After 6 Week Control PeriodBlood Pressurediastolic blood pressure87 mmHgStandard Deviation 10
After HIT AssessmentBlood Pressuresystolic blood pressure136 mmHgStandard Deviation 19
After HIT AssessmentBlood Pressurediastolic blood pressure78 mmHgStandard Deviation 8
p-value: 0.771ANOVA
p-value: 0.028ANOVA
Primary

Body Fat Mass Estimated Via Bioimpedance

total body fat and trunk fat estimated via bioimpedance measured after overnight fast, expressed as percentage

Time frame: Baseline, Follow up at 6 Weeks and following HIT intervention at 12 Weeks

ArmMeasureGroupValue (MEAN)Dispersion
Baseline AssessmentBody Fat Mass Estimated Via Bioimpedancetotal fat29.7 percentage body fatStandard Deviation 8.2
Baseline AssessmentBody Fat Mass Estimated Via Bioimpedancetrunk fat26.6 percentage body fatStandard Deviation 6
After 6 Week Control PeriodBody Fat Mass Estimated Via Bioimpedancetotal fat29.5 percentage body fatStandard Deviation 8.3
After 6 Week Control PeriodBody Fat Mass Estimated Via Bioimpedancetrunk fat29.1 percentage body fatStandard Deviation 5.4
After HIT AssessmentBody Fat Mass Estimated Via Bioimpedancetotal fat28.3 percentage body fatStandard Deviation 7.1
After HIT AssessmentBody Fat Mass Estimated Via Bioimpedancetrunk fat28.6 percentage body fatStandard Deviation 5.7
p-value: 0.092ANOVA
p-value: 0.101ANOVA
Primary

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)

Time frame: Baseline, Follow up at 6 Weeks and following HIT intervention at 12 Weeks

ArmMeasureValue (MEAN)Dispersion
Baseline AssessmentEstimated VO2 Max34.9 millilitres/kilogram/minuteStandard Deviation 6.5
After 6 Week Control PeriodEstimated VO2 Max37.6 millilitres/kilogram/minuteStandard Deviation 7.2
After HIT AssessmentEstimated VO2 Max38.5 millilitres/kilogram/minuteStandard Deviation 7.2
p-value: <0.001ANOVA
Primary

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

Time frame: Baseline, Follow up at 6 Weeks and following HIT intervention at 12 Weeks

ArmMeasureValue (MEAN)Dispersion
Baseline AssessmentExecutive Function (Verbal Fluency Test)8 wordsStandard Deviation 4
After 6 Week Control PeriodExecutive Function (Verbal Fluency Test)12 wordsStandard Deviation 4
After HIT AssessmentExecutive Function (Verbal Fluency Test)11 wordsStandard Deviation 3
p-value: 0.009ANOVA
Primary

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.

Time frame: Baseline, Follow up at 6 Weeks and following HIT intervention at 12 Weeks

ArmMeasureValue (MEAN)Dispersion
Baseline AssessmentFIB-40.68 Fibrosis ScoreStandard Deviation 0.18
After 6 Week Control PeriodFIB-40.60 Fibrosis ScoreStandard Deviation 0.19
After HIT AssessmentFIB-40.60 Fibrosis ScoreStandard Deviation 0.18
p-value: 0.023ANOVA
Primary

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

Time frame: Baseline, Follow up at 6 Weeks and following HIT intervention at 12 Weeks

ArmMeasureGroupValue (MEAN)Dispersion
Baseline AssessmentGeneral Well-being as Assessed by SF-36 QuestionnairePain78 units on a scaleStandard Deviation 13
Baseline AssessmentGeneral Well-being as Assessed by SF-36 QuestionnaireHealth Perception58 units on a scaleStandard Deviation 19
Baseline AssessmentGeneral Well-being as Assessed by SF-36 QuestionnairePhysical Role Limitation79 units on a scaleStandard Deviation 27
Baseline AssessmentGeneral Well-being as Assessed by SF-36 QuestionnaireChange in Health50 units on a scaleStandard Deviation 18
Baseline AssessmentGeneral Well-being as Assessed by SF-36 QuestionnairePhysical Function79 units on a scaleStandard Deviation 25
Baseline AssessmentGeneral Well-being as Assessed by SF-36 QuestionnaireEnergy/Vitality58 units on a scaleStandard Deviation 18
Baseline AssessmentGeneral Well-being as Assessed by SF-36 QuestionnaireMental Health71 units on a scaleStandard Deviation 17
Baseline AssessmentGeneral Well-being as Assessed by SF-36 QuestionnaireSocial Function78 units on a scaleStandard Deviation 31
Baseline AssessmentGeneral Well-being as Assessed by SF-36 QuestionnaireMental Role Limitation76 units on a scaleStandard Deviation 24
After 6 Week Control PeriodGeneral Well-being as Assessed by SF-36 QuestionnaireChange in Health53 units on a scaleStandard Deviation 15
After 6 Week Control PeriodGeneral Well-being as Assessed by SF-36 QuestionnairePhysical Function85 units on a scaleStandard Deviation 22
After 6 Week Control PeriodGeneral Well-being as Assessed by SF-36 QuestionnaireSocial Function82 units on a scaleStandard Deviation 27
After 6 Week Control PeriodGeneral Well-being as Assessed by SF-36 QuestionnaireMental Health69 units on a scaleStandard Deviation 20
After 6 Week Control PeriodGeneral Well-being as Assessed by SF-36 QuestionnairePain72 units on a scaleStandard Deviation 28
After 6 Week Control PeriodGeneral Well-being as Assessed by SF-36 QuestionnairePhysical Role Limitation79 units on a scaleStandard Deviation 31
After 6 Week Control PeriodGeneral Well-being as Assessed by SF-36 QuestionnaireMental Role Limitation76 units on a scaleStandard Deviation 34
After 6 Week Control PeriodGeneral Well-being as Assessed by SF-36 QuestionnaireEnergy/Vitality56 units on a scaleStandard Deviation 20
After 6 Week Control PeriodGeneral Well-being as Assessed by SF-36 QuestionnaireHealth Perception60 units on a scaleStandard Deviation 17
After HIT AssessmentGeneral Well-being as Assessed by SF-36 QuestionnaireMental Health77 units on a scaleStandard Deviation 20
After HIT AssessmentGeneral Well-being as Assessed by SF-36 QuestionnairePhysical Function92 units on a scaleStandard Deviation 16
After HIT AssessmentGeneral Well-being as Assessed by SF-36 QuestionnaireMental Role Limitation81 units on a scaleStandard Deviation 30
After HIT AssessmentGeneral Well-being as Assessed by SF-36 QuestionnaireSocial Function83 units on a scaleStandard Deviation 27
After HIT AssessmentGeneral Well-being as Assessed by SF-36 QuestionnaireHealth Perception61 units on a scaleStandard Deviation 17
After HIT AssessmentGeneral Well-being as Assessed by SF-36 QuestionnaireChange in Health67 units on a scaleStandard Deviation 18
After HIT AssessmentGeneral Well-being as Assessed by SF-36 QuestionnairePain88 units on a scaleStandard Deviation 16
After HIT AssessmentGeneral Well-being as Assessed by SF-36 QuestionnaireEnergy/Vitality64 units on a scaleStandard Deviation 21
After HIT AssessmentGeneral Well-being as Assessed by SF-36 QuestionnairePhysical Role Limitation90 units on a scaleStandard Deviation 22
p-value: 0.099ANOVA
p-value: 0.566ANOVA
p-value: 0.246ANOVA
p-value: 0.145ANOVA
p-value: 0.085ANOVA
p-value: 0.114ANOVA
p-value: 0.841ANOVA
p-value: 0.366ANOVA
p-value: 0.745ANOVA
Primary

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

Time frame: Baseline, Follow up at 6 Weeks and following HIT intervention at 12 Weeks

ArmMeasureValue (MEAN)Dispersion
Baseline AssessmentHomeostasis Model Assessment of Insulin Resistance (HOMA-IR)6.9 units on a scaleStandard Deviation 4.7
After 6 Week Control PeriodHomeostasis Model Assessment of Insulin Resistance (HOMA-IR)9.6 units on a scaleStandard Deviation 10.5
After HIT AssessmentHomeostasis Model Assessment of Insulin Resistance (HOMA-IR)7.0 units on a scaleStandard Deviation 4.3
p-value: 0.474ANOVA
Primary

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

Time frame: Baseline, Follow up at 6 Weeks and following HIT intervention at 12 Weeks

ArmMeasureValue (MEAN)Dispersion
Baseline AssessmentLong-term Memory Recall4 wordsStandard Deviation 1
After 6 Week Control PeriodLong-term Memory Recall5 wordsStandard Deviation 2
After HIT AssessmentLong-term Memory Recall5 wordsStandard Deviation 2
p-value: 0.513ANOVA
Primary

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.

Time frame: Baseline, Follow up at 6 Weeks and following HIT intervention at 12 Weeks

ArmMeasureValue (MEAN)Dispersion
Baseline AssessmentOral Glucose Tolerance Test981 mmol/L*minStandard Deviation 136
After 6 Week Control PeriodOral Glucose Tolerance Test1030 mmol/L*minStandard Deviation 182
After HIT AssessmentOral Glucose Tolerance Test1010 mmol/L*minStandard Deviation 247
p-value: 0.174ANOVA
Primary

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.

Time frame: Baseline, Follow up at 6 Weeks and following HIT intervention at 12 Weeks

ArmMeasureValue (MEAN)Dispersion
Baseline AssessmentPhysical Function-Get up and go Test6.61 secondsStandard Deviation 0.77
After 6 Week Control PeriodPhysical Function-Get up and go Test6.23 secondsStandard Deviation 0.59
After HIT AssessmentPhysical Function-Get up and go Test5.87 secondsStandard Deviation 0.63
p-value: 0.005ANOVA
Primary

Short-term Memory Recall

testing of verbal word presentation-immediate recall of 10 words (60 seconds for recall) Maximum =10, minimum =0

Time frame: Baseline, Follow up at 6 Weeks and following HIT intervention at 12 Weeks

ArmMeasureValue (MEAN)Dispersion
Baseline AssessmentShort-term Memory Recall6 wordsStandard Deviation 2
After 6 Week Control PeriodShort-term Memory Recall7 wordsStandard Deviation 1
After HIT AssessmentShort-term Memory Recall6 wordsStandard Deviation 2
p-value: 0.31ANOVA

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026