Trial Outcomes & Findings for The Effect of HIT in Patients With Non-alcoholic Fatty Liver Disease/Steatohepatitis (NCT NCT02528305)

NCT ID: NCT02528305

Last Updated: 2018-05-04

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 12 participants
• Primary outcome timeframe: Baseline, Follow up at 6 Weeks and following HIT intervention at 12 Weeks
• Results posted on: 2018-05-04

Participant Flow

Participant milestones

Measure	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.
Overall Study STARTED	12
Overall Study End of Control Period Assessment	11
Overall Study End of Intervention Period Assessment	9
Overall Study COMPLETED	9
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Measure	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.
Overall Study Withdrawal by Subject	1
Overall Study Adverse Event	1
Overall Study Physician Decision	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	High-intensity Interval Training (HIT) n=12 Participants 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.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	12 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	45 years STANDARD_DEVIATION 8 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants
height	1.71 metres STANDARD_DEVIATION 0.09 • n=5 Participants
body mass index (BMI)	29.6 kg/m^2 STANDARD_DEVIATION 3.8 • n=5 Participants
diagnosis Non-alcoholic Fatty Liver Disease (NAFLD)	7 participants n=5 Participants
diagnosis Non-alcoholic Steatohepatitis (NASH)	5 participants n=5 Participants

PRIMARY outcome

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

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

Outcome measures

Measure	Baseline Assessment n=9 Participants on entry to trial	After 6 Week Control Period n=9 Participants repeat assessment after 6 weeks of no intervention	After HIT Assessment n=9 Participants final assessment within 1 week of completing 6 weeks of HIT
Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)	6.9 units on a scale Standard Deviation 4.7	9.6 units on a scale Standard Deviation 10.5	7.0 units on a scale Standard Deviation 4.3

PRIMARY outcome

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

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.

Outcome measures

Measure	Baseline Assessment n=9 Participants on entry to trial	After 6 Week Control Period n=9 Participants repeat assessment after 6 weeks of no intervention	After HIT Assessment n=9 Participants final assessment within 1 week of completing 6 weeks of HIT
Oral Glucose Tolerance Test	981 mmol/L*min Standard Deviation 136	1030 mmol/L*min Standard Deviation 182	1010 mmol/L*min Standard Deviation 247

PRIMARY outcome

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

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.

Outcome measures

Measure	Baseline Assessment n=9 Participants on entry to trial	After 6 Week Control Period n=9 Participants repeat assessment after 6 weeks of no intervention	After HIT Assessment n=9 Participants final assessment within 1 week of completing 6 weeks of HIT
AST: ALT Ratio	0.5 ratio Standard Deviation 0.2	0.5 ratio Standard Deviation 0.2	0.5 ratio Standard Deviation 0.2

PRIMARY outcome

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

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.

Outcome measures

Measure	Baseline Assessment n=9 Participants on entry to trial	After 6 Week Control Period n=9 Participants repeat assessment after 6 weeks of no intervention	After HIT Assessment n=9 Participants final assessment within 1 week of completing 6 weeks of HIT
FIB-4	0.68 Fibrosis Score Standard Deviation 0.18	0.60 Fibrosis Score Standard Deviation 0.19	0.60 Fibrosis Score Standard Deviation 0.18

PRIMARY outcome

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

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

Outcome measures

Measure	Baseline Assessment n=9 Participants on entry to trial	After 6 Week Control Period n=9 Participants repeat assessment after 6 weeks of no intervention	After HIT Assessment n=9 Participants final assessment within 1 week of completing 6 weeks of HIT
Body Fat Mass Estimated Via Bioimpedance total fat	29.7 percentage body fat Standard Deviation 8.2	29.5 percentage body fat Standard Deviation 8.3	28.3 percentage body fat Standard Deviation 7.1
Body Fat Mass Estimated Via Bioimpedance trunk fat	26.6 percentage body fat Standard Deviation 6.0	29.1 percentage body fat Standard Deviation 5.4	28.6 percentage body fat Standard Deviation 5.7

PRIMARY outcome

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

taken with participant supine, measured on left arm

Outcome measures

Measure	Baseline Assessment n=9 Participants on entry to trial	After 6 Week Control Period n=9 Participants repeat assessment after 6 weeks of no intervention	After HIT Assessment n=9 Participants final assessment within 1 week of completing 6 weeks of HIT
Blood Pressure systolic blood pressure	139 mmHg Standard Deviation 18	142 mmHg Standard Deviation 13	136 mmHg Standard Deviation 19
Blood Pressure diastolic blood pressure	85 mmHg Standard Deviation 13	87 mmHg Standard Deviation 10	78 mmHg Standard Deviation 8

PRIMARY outcome

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

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

Outcome measures

Measure	Baseline Assessment n=9 Participants on entry to trial	After 6 Week Control Period n=9 Participants repeat assessment after 6 weeks of no intervention	After HIT Assessment n=9 Participants final assessment within 1 week of completing 6 weeks of HIT
General Well-being as Assessed by SF-36 Questionnaire Pain	78 units on a scale Standard Deviation 13	72 units on a scale Standard Deviation 28	88 units on a scale Standard Deviation 16
General Well-being as Assessed by SF-36 Questionnaire Physical Function	79 units on a scale Standard Deviation 25	85 units on a scale Standard Deviation 22	92 units on a scale Standard Deviation 16
General Well-being as Assessed by SF-36 Questionnaire Social Function	78 units on a scale Standard Deviation 31	82 units on a scale Standard Deviation 27	83 units on a scale Standard Deviation 27
General Well-being as Assessed by SF-36 Questionnaire Mental Health	71 units on a scale Standard Deviation 17	69 units on a scale Standard Deviation 20	77 units on a scale Standard Deviation 20
General Well-being as Assessed by SF-36 Questionnaire Change in Health	50 units on a scale Standard Deviation 18	53 units on a scale Standard Deviation 15	67 units on a scale Standard Deviation 18
General Well-being as Assessed by SF-36 Questionnaire Physical Role Limitation	79 units on a scale Standard Deviation 27	79 units on a scale Standard Deviation 31	90 units on a scale Standard Deviation 22
General Well-being as Assessed by SF-36 Questionnaire Mental Role Limitation	76 units on a scale Standard Deviation 24	76 units on a scale Standard Deviation 34	81 units on a scale Standard Deviation 30
General Well-being as Assessed by SF-36 Questionnaire Energy/Vitality	58 units on a scale Standard Deviation 18	56 units on a scale Standard Deviation 20	64 units on a scale Standard Deviation 21
General Well-being as Assessed by SF-36 Questionnaire Health Perception	58 units on a scale Standard Deviation 19	60 units on a scale Standard Deviation 17	61 units on a scale Standard Deviation 17

PRIMARY outcome

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

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

Outcome measures

Measure	Baseline Assessment n=9 Participants on entry to trial	After 6 Week Control Period n=9 Participants repeat assessment after 6 weeks of no intervention	After HIT Assessment n=9 Participants final assessment within 1 week of completing 6 weeks of HIT
Short-term Memory Recall	6 words Standard Deviation 2	7 words Standard Deviation 1	6 words Standard Deviation 2

PRIMARY outcome

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

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)

Outcome measures

Measure	Baseline Assessment n=9 Participants on entry to trial	After 6 Week Control Period n=9 Participants repeat assessment after 6 weeks of no intervention	After HIT Assessment n=9 Participants final assessment within 1 week of completing 6 weeks of HIT
Estimated VO2 Max	34.9 millilitres/kilogram/minute Standard Deviation 6.5	37.6 millilitres/kilogram/minute Standard Deviation 7.2	38.5 millilitres/kilogram/minute Standard Deviation 7.2

PRIMARY outcome

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

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.

Outcome measures

Measure	Baseline Assessment n=9 Participants on entry to trial	After 6 Week Control Period n=9 Participants repeat assessment after 6 weeks of no intervention	After HIT Assessment n=9 Participants final assessment within 1 week of completing 6 weeks of HIT
Physical Function-"Get up and go" Test	6.61 seconds Standard Deviation 0.77	6.23 seconds Standard Deviation 0.59	5.87 seconds Standard Deviation 0.63

PRIMARY outcome

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

ratio of blood pressure in left arm and right ankle

Outcome measures

Measure	Baseline Assessment n=9 Participants on entry to trial	After 6 Week Control Period n=9 Participants repeat assessment after 6 weeks of no intervention	After HIT Assessment n=9 Participants final assessment within 1 week of completing 6 weeks of HIT
Ankle Brachial Pressure Index (ABPI)	1.15 ABPI Standard Deviation 0.16	1.08 ABPI Standard Deviation 0.18	1.13 ABPI Standard Deviation 0.27

PRIMARY outcome

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

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

Outcome measures

Measure	Baseline Assessment n=9 Participants on entry to trial	After 6 Week Control Period n=9 Participants repeat assessment after 6 weeks of no intervention	After HIT Assessment n=9 Participants final assessment within 1 week of completing 6 weeks of HIT
Long-term Memory Recall	4 words Standard Deviation 1	5 words Standard Deviation 2	5 words Standard Deviation 2

PRIMARY outcome

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

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

Outcome measures

Measure	Baseline Assessment n=9 Participants on entry to trial	After 6 Week Control Period n=9 Participants repeat assessment after 6 weeks of no intervention	After HIT Assessment n=9 Participants final assessment within 1 week of completing 6 weeks of HIT
Executive Function (Verbal Fluency Test)	8 words Standard Deviation 4	12 words Standard Deviation 4	11 words Standard Deviation 3

Adverse Events

High-intensity Interval Training (HIT)

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure

High-intensity Interval Training (HIT) n=12 participants at risk 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.

Cardiac disorders Myocardial Infarction

8.3% 1/12 • Number of events 1

Other adverse events

Adverse event data not reported

Additional Information

Dr Niels Vollaard

University of Striling

Phone: +441786466488

Email: n.vollaard@stir.ac.uk

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place