PONE-D-24-40480Time-restricted eating in early-stage Huntington’s disease: A 12-week interventional clinical trial protocolPLOS ONE

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Academic Editor

PLOS ONE

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Additional Editor Comments:

Looking good. Please also see and respond to the comments below:

This study protocol intends on examining the feasibility and safety of time-restricted eating (TRE) in 25 patients with Huntington’s disease.

Conclusion

Overall, this study protocol is well thought through and although the number of participants is small, this study will bring exciting results on the impact of nutrition and lifestyle interventions in neurodegenerative diseases.

Comments

· Figure 1 and table 1 are overlapping, it will be more beneficial to integrate the information of the table into the figure and have a better overview

· The self-selection of the eating window light is not ideal to see beneficial changes in a small study sample, however, I agree that it might not be feasible to impose an eating window

· Exclusion criteria: maybe add history of eating disorder as exclusion criteria

· Additional sample collection during the 12 weeks would be of great interest to track possible changes induced by TRE, rather than only checking before and after

192 Are not weight stable…

207 NfL abbreviation only introduced in line 308

243 Only these values? Maybe include an extensive list of what will be measured

247 What other questionnaires are included? Well-being etc. Include list with questionnaires and references

265 Were there clear instructions on zero-calorie beverages with sweeteners?

281 Why only kcal and macronutrient composition? The quality of the food (e.g. highly processed) and the micronutrient composition are of great interest and should be considered as well.

455 This is not the first intervention trial looking ate the effects of TRE in neurodegenerative diseases: Hansen B, Laczny CC, Aho VTE, et al Protocol for a multicentre cross-sectional, longitudinal ambulatory clinical trial in rheumatoid arthritis and Parkinson’s disease patients analysing the relation between the gut microbiome, fasting and immune status in Germany (ExpoBiome) BMJ Open 2023;13:e071380. doi: 10.1136/bmjopen-2022-071380

TABLE 1 Why are no dietary questionnaires and sleep etc. tracked on baseline visit?

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #1: Yes

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2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #1: Yes

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3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible.

Reviewer #1: Yes

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4. Have the authors described where all data underlying the findings will be made available when the study is complete?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: This is a well designed and well written protocol for time-restricted eating in early-stage Huntington’s disease. However, I have a few comments.

1. It is a single arm study. Therefore, it is useful to cite any matching reference in the literature for placebo to compare the results to get an initial preliminary idea to proceed with large two arm trials.

2. Participants will be allowed to self-select the timing of the eating window. I understand that it is to study the feasibility of the intervention. However, is not it better to recommend participants for internment fasting window from late afternoon until next morning to match with the circadian rhythm of the body?

3. In line 116: separate the objectives as primary, secondary, exploratory etc.

4. Minimum age for inclusion is at least 21 years. Why not 18-years?

5. How likely to have any participants who are not fluent in English and needs translator. If so, are they going to be excluded?

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Reviewer #1: Yes:  Dr Shah-Jalal Sarker

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Time-restricted eating in early-stage Huntington’s disease: A 12-week interventional clinical trial protocol

PONE-D-24-40480R1

Dear Dr. Wells,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Kind regards,

Prof. Jussi Sipilä, M.D., Ph.D., B.Soc.Sci.

Academic Editor

PLOS ONE

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #1: Yes

**********

2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #1: Yes

**********

3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible.

Reviewer #1: Yes

**********

4. Have the authors described where all data underlying the findings will be made available when the study is complete?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The authors have applied all of my comments appropriately. I have no other comments to make. The article is ready to be accepted.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean? ). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy .

Reviewer #1: Yes:  Dr Shah-Jalal Sarker

**********