PONE-D-24-36320The effect of melatonin supplementation on the plasma levels of 2-arachidonoylglycerol, ghrelin and hedonic eating intensity in overweight/obese females: a study protocol for a pilot randomized controlled trialPLOS ONE

Dear Dr. Pourghassem Gargari,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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Kind regards,

Marcello Iriti, Ph.D.

Academic Editor

PLOS ONE

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2. Thank you for stating the following financial disclosure: 

The funding for the trial received support from Tabriz University of Medical Sciences under grant number IR.TBZMED.REC.1402.075.

Please state what role the funders took in the study.  If the funders had no role, please state: "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript." 

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3. Thank you for stating the following in the Acknowledgments Section of your manuscript: 

This protocol is the second phase of a Ph.D. dissertation registered at Tabriz University of Medical Sciences, Tabriz, Iran, with the registration number IR.TBZMED.REC.1402.075.

We note that you have provided funding information that is not currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form. 

Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows: 

The funding for the trial received support from Tabriz University of Medical Sciences under grant number IR.TBZMED.REC.1402.075.

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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

Reviewer #2: 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

Reviewer #2: 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

Reviewer #2: 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

Reviewer #2: 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

Reviewer #2: 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:  The authors intend to conduct a randomized, double-blinded, placebo-controlled study to investigate the effect of melatonin supplementation on plasma levels of 2-arachidonylglycerol and ghrelin, and intensity of hedonic eating. They will recruit forty-six women, randomly assigned to two arms: melatonin supplement or placebo with balanced design for 8 weeks. Data will be analyzed with ANCOVA.

1. Line 101. “46 subjects (23 in each group)”. The determined sample size seems quite arbitrary. What effect size can be detected by this sample size?

2. Line 114. “apparently healthy volunteers”. This sounds very subjective. Need to clarify how to define apparently healthy.

3. Line 148. “if any adverse events occur, unblinding is allowed”. Please clarify whether these participants will be included in the analysis.

4. Line 233. “log transformation will be applied to normalize variable”. As you do not know the distribution of variables yet, how do you know log-transformation will be appropriate?

Reviewer #2:  Dear Editor,

Thank you for inviting me to review this manuscript. I appreciate the opportunity to contribute to the peer review process for this study

General comments : The study makes a valuable contribution by investigating the effects of melatonin on hedonic eating in overweight/obese women, addressing an important gap in the literature. The introduction provides a strong background and context, with a clear and logical flow that lays a solid foundation for the research and leads smoothly to the study's main objective. The study design is robust, and the intervention plan is clearly defined. However, since the manuscript does not present any results, it limits the ability to fully evaluate the outcomes and implications of the research. Despite this, I believe this is an excellent study that could provide meaningful insights into the role of melatonin in eating behavior. However, there are some improvements that should be made prior to publishing.

Point 1 #In the introduction section, I suggest adding a line or two to briefly describe the PFS and explain its specific relevance to hedonic eating studies.

Point 2 # Could you clarify how the number of 46 participants was determined? It would be helpful to provide more details on how the sample size was calculated, and whether a power analysis was conducted. Also, please explain how the 15% attrition rate was estimated.

Point 2 # While you have have outlined a comprehensive set of inclusion and exclusion criteria, it’s still unclear how these have been verified during screening.

Point 3 #The block size is mentioned as two. It might be helpful to confirm that this approach maintains the required balance across groups, as the small block size may not provide sufficient flexibility to ensure even distribution, particularly toward the end of the randomization process.

Point 4# It’s good that one author (RM) created the randomization sequence without being involved in assigning participants. This could be even stronger if it’s mentioned whether they are also blinded to any participant details or baseline data to reduce bias further.

Point 5 # Please specify the software used for randomization.

Point 6# Specify the purpose of bi-weekly follow-up calls.

Point 7# Please clarify if there’s a standard method for counting and recording any unused tablets at each checkpoint to help ensure accurate tracking of compliance.

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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: No

Reviewer #2: No

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The effect of melatonin supplementation on the plasma levels of 2-arachidonoylglycerol, ghrelin and hedonic eating intensity in overweight/obese females: a study protocol for a pilot randomized controlled trial

PONE-D-24-36320R1

Dear Dr. Pourghassem Gargari,

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.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager®  and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Marcello Iriti, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

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

Reviewer #2: 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

Reviewer #2: 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

Reviewer #2: 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

Reviewer #2: 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

Reviewer #2: 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: Thank you for addressing the raised comments and made the edits accordingly. This reviewer has no further concern.

Reviewer #2: Dear Editor,

Thank you again for inviting me to review the revised manuscript for your esteemed journal.

The manuscript, titled « The effect of melatonin supplementation on the plasma levels of 2- arachidonoylglycerol, ghrelin and hedonic eating intensity in overweight/obese females: a study protocol for a pilot randomized controlled trial » (Manuscript ID: PONE-D-24-36320R1)," by Malihe Karamizadeh et al., has been appropriately revised. The authors have adequately addressed all the concerns raised. I find the revised manuscript to be well-prepared and scientifically robust. Therefore, I believe it merits publication in PLOS One.

Dear Authors, I have no further comments. Thank you for your efforts in addressing the previous concerns.

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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: No

Reviewer #2: No

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