Reviewer ’s report  
 
Title: High -intensity interval training and moderate -intensity continuous training in adults with 
Crohn’s disease: a pilot  randomised controlled trial  
 
Version: 0 Date: 19 Oct 2018  
 
Reviewer: Jessica Elia  
 
Reviewer's report:  
 
General Comments:  
Strengths:  
1. This study investigates the impact of aerobic exercise in the Crohn's population.  Well 
designed, objective IBD exercise studies including standardized physiologic and  
inflammatory outcome measures are lacking and needed.  
2. This study includes a wide array of objective measures.  
3. This study includes supervised exercise and a suitable follow -up period.  
 
Weaknesses  
1. The methodology of this study is unclear.  Study su bjects were "invited" to participate in 
supervised exercise sessions.  What were the instructions exactly?  Was there a 
mandatory minimum the subjects were expected to complete?  Were the subjects allowed 
to exercise outside the supervised sessions?  What were the instructions after the initial 
12 week supervised sessions?  Were subjects  expected to continue independently or was 
continued exercise optional?   
a. Methodology should also include what the HIIT subjects performed between 
intervals.  
b. HIIT sub jects defined RPE as "hard."  HIIT is defined as "all out" or "extremely 
hard."  Should this be redefined as "modified HIIT" as heart rate is unreliable in 
IBD subjects due to dysautonomia?  
2. This study does not provide all objective data collected with a nalysis.  Were the changes 
seen from baseline, 3, and 6 months statistically significant?  Where is the FS data for 
pre, post, and 10 minutes post exercise (as stated in previously published pilot)?  For 
example, based on Table 3, fatigue scores for both H IIT and MICT patients increased 
from baseline to three months.  Were these changes statistically significant?  Fatigue and 
over fatigue following exercise is a concern in IBD subject exercise prescription and 
should be addressed.  Please address all result s (including biomarkers, these are important 
for disease inflammation, especially given adverse events) numerically as well as with 
interview results.  
3. Safety is a concern.   
a. HITT: Consider that this study population consisted of stable, no or low -
inflammation, few co -morbidity, Crohn's patients; a large percentage of whom 
were in employed.  This is a high functioning group.  This study does not include 
a threshold for patient safety acceptability.  3 adverse events occurred during 
HIIT training with 2 subjects.  2/13 subjects (15%) experienced adverse effects of 
headache, dizziness, and vomiting.  IBD subject safety issues stem from 
physiologic concerns of dehydration, fatigue/over fatigue and autonomic 
dysfunction.   
1. Once a subject had an adverse outcome, was removal from the study considered?  Was subject 
removal from the study considered after the second adverse outcome?  Were steps taken to 
prevent another episode?  
2. This should be addressed in the discussion.  Add to this number a disease flar e in the follow 
up period, 3/13 (23%).  Either way this is not a safe intervention for IBD subjects.  It may be 
cautiously considered for a high -functioning sub -population of IBD subjects under close 
supervision, but re -thinking a pre -training period to es tablish a baseline of athletic suitability 
should be considered.    
b. MICT: 1 disease flare in the follow -up period.  Moderate aerobic training has been shown to 
prevent flares in CD.  1/12 should be considered.  Is this an anomaly?  Was training too 
regimented/difficult?  Would a range of RPE depending upon subject daily sx be a better 
strategy?  
 
Additional Comments:  
 
1. "...groups were offered..." Page 3, Line 35 Were the subjects offered supervised exercise?  
What were the instructions?  Minimum number required?  Supposed to attend all three?  What 
were post 12 week instructions?  Encouraged to continue?  Instructed to continue?  Please 
clarify.  
2. EXACT follow journal style for abbreviations, write full length meaning first.  Page 4, Line 79  
3. "...cycle ergometer..." Page 6, Line 127 Clarify lower body cycle ergometer  
4. Page 6, Line 127 -130 Clarify performance of HIIT participants between intervals  
5. "RPE -C, RPE -L" Page 7, Line 133 please define terms  
6. Borg Scale Page 7 Initial Pilot stat ed Borg Scale 6 -20, please state clarification  
7. "encouraged to continue" exact language please.  instructed to continue?  What was the 
expectation? Page 7, Line 138  
10. Please include all trial data, biomarker data speaks to disease inflammation.  This  is an 
important component of the study.   
a. Please include statistical analysis of all data results, cannot evaluate results without statistics.   
b. It appears the subjects became more fatigued with the exercise program and less fatigued after 
it was ov er...is this significant?   
c. Were the ventilation or peak oxygen changes statistically significant compared to controls or 
between groups?   
d. Please provide same for body mass, waist circumference, resting heart rate, etc. in addition to 
interview comm ents 
10. HITT subjects RPE "hard" is this really "HIIT"? Page 12, Line 269 -275 
11. Figure 1 Please clarify 2 subjects with disease flares on follow -up, difficult to discern  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an add itional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I recommend additional statistical review  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections before being published  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an  
organisation that may in any way ga in or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose  
financially from the publication of this manuscript, either now or in the f uture?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the  
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds  or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I  declare that I have no competing interests' 
below.  If your reply is yes to any, please give details below.  
 
I declare that I have no co mpeting interests'  
 
I agree to the open peer review policy of the journal. I understand that my name will be included  
on m y report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. I agree for my report to be made available under an Open Access Creative Commons  
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments  
which I do not wish to be included in my named report can be included as confidential comments  
to the editors, which will not be published.  
 
I agree  to the open peer review policy of the journal  
 
 
 
Reviewer ’s report  
 
Title: High -intensity interval training and moderate -intensity continuous training in adults with 
Crohn’s disease: a pilot  randomised controlled trial  
 
Version: 0 Date: 19 Oct 2018  
 
Reviewer: Jessica Elia  
 
Reviewer's report:  
 
General Comments:  
Strengths:  
1. This study investigates the impact of aerobic exercise in the Crohn's population.  Well 
designed, objective IBD exercise studies including standardized physiologic and  
inflammatory outcome measures are lacking and needed.  
2. This study includes a wide array of objective measures.  
3. This study includes supervised exercise and a suitable follow -up period.  
 
Weaknesses  
1. The methodology of this study is unclear.  Study su bjects were "invited" to participate in 
supervised exercise sessions.  What were the instructions exactly?  Was there a 
mandatory minimum the subjects were expected to complete?  Were the subjects allowed 
to exercise outside the supervised sessions?  What were the instructions after the initial 
12 week supervised sessions?  Were subjects  expected to continue independently or was 
continued exercise optional?   
a. Methodology should also include what the HIIT subjects performed between 
intervals.  
b. HIIT sub jects defined RPE as "hard."  HIIT is defined as "all out" or "extremely 
hard."  Should this be redefined as "modified HIIT" as heart rate is unreliable in 
IBD subjects due to dysautonomia?  
2. This study does not provide all objective data collected with a nalysis.  Were the changes 
seen from baseline, 3, and 6 months statistically significant?  Where is the FS data for 
pre, post, and 10 minutes post exercise (as stated in previously published pilot)?  For 
example, based on Table 3, fatigue scores for both H IIT and MICT patients increased 
from baseline to three months.  Were these changes statistically significant?  Fatigue and 
over fatigue following exercise is a concern in IBD subject exercise prescription and 
should be addressed.  Please address all result s (including biomarkers, these are important 
for disease inflammation, especially given adverse events) numerically as well as with 
interview results.  
3. Safety is a concern.   
a. HITT: Consider that this study population consisted of stable, no or low -
inflammation, few co -morbidity, Crohn's patients; a large percentage of whom 
were in employed.  This is a high functioning group.  This study does not include 
a threshold for patient safety acceptability.  3 adverse events occurred during 
HIIT training with 2 subjects.  2/13 subjects (15%) experienced adverse effects of 
headache, dizziness, and vomiting.  IBD subject safety issues stem from 
physiologic concerns of dehydration, fatigue/over fatigue and autonomic 
dysfunction.   
1. Once a subject had an adverse outcome, was removal from the study considered?  Was subject 
removal from the study considered after the second adverse outcome?  Were steps taken to 
prevent another episode?  
2. This should be addressed in the discussion.  Add to this number a disease flar e in the follow 
up period, 3/13 (23%).  Either way this is not a safe intervention for IBD subjects.  It may be 
cautiously considered for a high -functioning sub -population of IBD subjects under close 
supervision, but re -thinking a pre -training period to es tablish a baseline of athletic suitability 
should be considered.    
b. MICT: 1 disease flare in the follow -up period.  Moderate aerobic training has been shown to 
prevent flares in CD.  1/12 should be considered.  Is this an anomaly?  Was training too 
regimented/difficult?  Would a range of RPE depending upon subject daily sx be a better 
strategy?  
 
Additional Comments:  
 
1. "...groups were offered..." Page 3, Line 35 Were the subjects offered supervised exercise?  
What were the instructions?  Minimum number required?  Supposed to attend all three?  What 
were post 12 week instructions?  Encouraged to continue?  Instructed to continue?  Please 
clarify.  
2. EXACT follow journal style for abbreviations, write full length meaning first.  Page 4, Line 79  
3. "...cycle ergometer..." Page 6, Line 127 Clarify lower body cycle ergometer  
4. Page 6, Line 127 -130 Clarify performance of HIIT participants between intervals  
5. "RPE -C, RPE -L" Page 7, Line 133 please define terms  
6. Borg Scale Page 7 Initial Pilot stat ed Borg Scale 6 -20, please state clarification  
7. "encouraged to continue" exact language please.  instructed to continue?  What was the 
expectation? Page 7, Line 138  
10. Please include all trial data, biomarker data speaks to disease inflammation.  This  is an 
important component of the study.   
a. Please include statistical analysis of all data results, cannot evaluate results without statistics.   
b. It appears the subjects became more fatigued with the exercise program and less fatigued after 
it was ov er...is this significant?   
c. Were the ventilation or peak oxygen changes statistically significant compared to controls or 
between groups?   
d. Please provide same for body mass, waist circumference, resting heart rate, etc. in addition to 
interview comm ents 
10. HITT subjects RPE "hard" is this really "HIIT"? Page 12, Line 269 -275 
11. Figure 1 Please clarify 2 subjects with disease flares on follow -up, difficult to discern  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an add itional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I recommend additional statistical review  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections before being published  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an  
organisation that may in any way ga in or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose  
financially from the publication of this manuscript, either now or in the f uture?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the  
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds  or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I  declare that I have no competing interests' 
below.  If your reply is yes to any, please give details below.  
 
I declare that I have no co mpeting interests'  
 
I agree to the open peer review policy of the journal. I understand that my name will be included  
on m y report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. I agree for my report to be made available under an Open Access Creative Commons  
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments  
which I do not wish to be included in my named report can be included as confidential comments  
to the editors, which will not be published.  
 
I agree  to the open peer review policy of the journal  
 
 
 
Please review this paper.
user
Reviewer ’s report  
 
Title: High -intensity interval training and moderate -intensity continuous training in adults with 
Crohn’s disease: a pilot  randomised controlled trial  
 
Version: 0 Date: 19 Oct 2018  
 
Reviewer: Jessica Elia  
 
Reviewer's report:  
 
General Comments:  
Strengths:  
1. This study investigates the impact of aerobic exercise in the Crohn's population.  Well 
designed, objective IBD exercise studies including standardized physiologic and  
inflammatory outcome measures are lacking and needed.  
2. This study includes a wide array of objective measures.  
3. This study includes supervised exercise and a suitable follow -up period.  
 
Weaknesses  
1. The methodology of this study is unclear.  Study su bjects were "invited" to participate in 
supervised exercise sessions.  What were the instructions exactly?  Was there a 
mandatory minimum the subjects were expected to complete?  Were the subjects allowed 
to exercise outside the supervised sessions?  What were the instructions after the initial 
12 week supervised sessions?  Were subjects  expected to continue independently or was 
continued exercise optional?   
a. Methodology should also include what the HIIT subjects performed between 
intervals.  
b. HIIT sub jects defined RPE as "hard."  HIIT is defined as "all out" or "extremely 
hard."  Should this be redefined as "modified HIIT" as heart rate is unreliable in 
IBD subjects due to dysautonomia?  
2. This study does not provide all objective data collected with a nalysis.  Were the changes 
seen from baseline, 3, and 6 months statistically significant?  Where is the FS data for 
pre, post, and 10 minutes post exercise (as stated in previously published pilot)?  For 
example, based on Table 3, fatigue scores for both H IIT and MICT patients increased 
from baseline to three months.  Were these changes statistically significant?  Fatigue and 
over fatigue following exercise is a concern in IBD subject exercise prescription and 
should be addressed.  Please address all result s (including biomarkers, these are important 
for disease inflammation, especially given adverse events) numerically as well as with 
interview results.  
3. Safety is a concern.   
a. HITT: Consider that this study population consisted of stable, no or low -
inflammation, few co -morbidity, Crohn's patients; a large percentage of whom 
were in employed.  This is a high functioning group.  This study does not include 
a threshold for patient safety acceptability.  3 adverse events occurred during 
HIIT training with 2 subjects.  2/13 subjects (15%) experienced adverse effects of 
headache, dizziness, and vomiting.  IBD subject safety issues stem from 
physiologic concerns of dehydration, fatigue/over fatigue and autonomic 
dysfunction.   
1. Once a subject had an adverse outcome, was removal from the study considered?  Was subject 
removal from the study considered after the second adverse outcome?  Were steps taken to 
prevent another episode?  
2. This should be addressed in the discussion.  Add to this number a disease flar e in the follow 
up period, 3/13 (23%).  Either way this is not a safe intervention for IBD subjects.  It may be 
cautiously considered for a high -functioning sub -population of IBD subjects under close 
supervision, but re -thinking a pre -training period to es tablish a baseline of athletic suitability 
should be considered.    
b. MICT: 1 disease flare in the follow -up period.  Moderate aerobic training has been shown to 
prevent flares in CD.  1/12 should be considered.  Is this an anomaly?  Was training too 
regimented/difficult?  Would a range of RPE depending upon subject daily sx be a better 
strategy?  
 
Additional Comments:  
 
1. "...groups were offered..." Page 3, Line 35 Were the subjects offered supervised exercise?  
What were the instructions?  Minimum number required?  Supposed to attend all three?  What 
were post 12 week instructions?  Encouraged to continue?  Instructed to continue?  Please 
clarify.  
2. EXACT follow journal style for abbreviations, write full length meaning first.  Page 4, Line 79  
3. "...cycle ergometer..." Page 6, Line 127 Clarify lower body cycle ergometer  
4. Page 6, Line 127 -130 Clarify performance of HIIT participants between intervals  
5. "RPE -C, RPE -L" Page 7, Line 133 please define terms  
6. Borg Scale Page 7 Initial Pilot stat ed Borg Scale 6 -20, please state clarification  
7. "encouraged to continue" exact language please.  instructed to continue?  What was the 
expectation? Page 7, Line 138  
10. Please include all trial data, biomarker data speaks to disease inflammation.  This  is an 
important component of the study.   
a. Please include statistical analysis of all data results, cannot evaluate results without statistics.   
b. It appears the subjects became more fatigued with the exercise program and less fatigued after 
it was ov er...is this significant?   
c. Were the ventilation or peak oxygen changes statistically significant compared to controls or 
between groups?   
d. Please provide same for body mass, waist circumference, resting heart rate, etc. in addition to 
interview comm ents 
10. HITT subjects RPE "hard" is this really "HIIT"? Page 12, Line 269 -275 
11. Figure 1 Please clarify 2 subjects with disease flares on follow -up, difficult to discern  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an add itional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I recommend additional statistical review  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections before being published  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an  
organisation that may in any way ga in or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose  
financially from the publication of this manuscript, either now or in the f uture?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the  
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds  or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I  declare that I have no competing interests' 
below.  If your reply is yes to any, please give details below.  
 
I declare that I have no co mpeting interests'  
 
I agree to the open peer review policy of the journal. I understand that my name will be included  
on m y report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. I agree for my report to be made available under an Open Access Creative Commons  
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments  
which I do not wish to be included in my named report can be included as confidential comments  
to the editors, which will not be published.  
 
I agree  to the open peer review policy of the journal  
 
 
 
assistant