NCT03740087

Brief Summary

Background: Foods derived from plants and animals contain miRNAs, and, some reports have detected diet-derived miRNAs circulating in mammalian serum. It is still unclear if the miRNAs present in food can be absorbed by the gastrointestinal tract and brought to the tissues to perform regulatory functions. The transfer of functional exogenous miRNA has been demonstrated in bacterial and viral infections but it is less well characterized in mammals. Edible bovine tissues contain unique profiles of human-homologous miRNAs that withstand cooking. If miRNAs from other species can cross the gastrointestinal barrier, it could have implications in gene regulation and health. Objective: Determine whether miRNAs from beef cross the gastrointestinal barrier and are transferred to human plasma. Methods: The investigators obtained fasting plasma from 29 healthy subjects divided in two groups: the omnivore group (6 men, 8 women) and the vegan group (8 men, 7 women; control group). Each participant was given a standard meal with or without beef depending on their group, then the plasma was collected at 2, 4 and 6 hours after the meal. The changes in the levels of of miR-1, miR-10b, miR-22, miR-92 and miR-192 were analysed by quantitative Polymerase Chain Reaction (qPCR).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
29

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started Apr 2015

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 13, 2015

Completed
7 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 16, 2015

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

May 22, 2016

Completed
2.5 years until next milestone

First Submitted

Initial submission to the registry

November 6, 2018

Completed
8 days until next milestone

First Posted

Study publicly available on registry

November 14, 2018

Completed
Last Updated

November 15, 2018

Status Verified

November 1, 2018

Enrollment Period

7 months

First QC Date

November 6, 2018

Last Update Submit

November 13, 2018

Conditions

Keywords

miRNAXenomirsDietVegan

Outcome Measures

Primary Outcomes (1)

  • Relative amount of miR-1, miR-10b, miR-22, miR-92 and miR-192 in plasma

    Quantification of miR-1, miR-10b, miR-22, miR-92 and miR-192 in plasma after meal time

    Change from Baseline microRNA levels at 2, 4 and 6 hours after intervention

Study Arms (2)

Omnivorous diet

EXPERIMENTAL

This group was assigned a meal containing beef (test meal) that consisted of 200 g roast beef with salad (lettuce, tomato, lentils) and a cup of rice.

Other: Omnivorous diet

Vegan diet

ACTIVE COMPARATOR

This group was assigned a control meal consisted of salad (lettuce, tomato, lentils) and a cup of rice.

Other: Vegan diet

Interventions

Determine if the transfer of bovine miRNAs is carried out after a meal containing beef.

Omnivorous diet

Used as a baseline for miRNA levels in blood

Vegan diet

Eligibility Criteria

Age18 Years - 30 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • For omnivorous subjects was that they should consume beef at least three times per week.
  • For vegan subjects was that they should have followed a strict vegan diet for at least one year

You may not qualify if:

  • For all subjects included pregnancy, menstruation during study sample collection, use of medicine or food supplements, intestinal malabsorption and intolerance to ingredients included in the diet intervention.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Cristina Rodriguez-Padilla

Monterrey, Nuevo León, 66455, Mexico

Location

Related Publications (18)

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    PMID: 24833329BACKGROUND
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    PMID: 15852042BACKGROUND
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    PMID: 19165215BACKGROUND
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    PMID: 20661255BACKGROUND
  • Kroh EM, Parkin RK, Mitchell PS, Tewari M. Analysis of circulating microRNA biomarkers in plasma and serum using quantitative reverse transcription-PCR (qRT-PCR). Methods. 2010 Apr;50(4):298-301. doi: 10.1016/j.ymeth.2010.01.032. Epub 2010 Feb 8.

    PMID: 20146939BACKGROUND
  • Kosaka N, Izumi H, Sekine K, Ochiya T. microRNA as a new immune-regulatory agent in breast milk. Silence. 2010 Mar 1;1(1):7. doi: 10.1186/1758-907X-1-7.

    PMID: 20226005BACKGROUND
  • Kuwabara Y, Ono K, Horie T, Nishi H, Nagao K, Kinoshita M, Watanabe S, Baba O, Kojima Y, Shizuta S, Imai M, Tamura T, Kita T, Kimura T. Increased microRNA-1 and microRNA-133a levels in serum of patients with cardiovascular disease indicate myocardial damage. Circ Cardiovasc Genet. 2011 Aug 1;4(4):446-54. doi: 10.1161/CIRCGENETICS.110.958975. Epub 2011 Jun 2.

    PMID: 21642241BACKGROUND
  • Zhang L, Hou D, Chen X, Li D, Zhu L, Zhang Y, Li J, Bian Z, Liang X, Cai X, Yin Y, Wang C, Zhang T, Zhu D, Zhang D, Xu J, Chen Q, Ba Y, Liu J, Wang Q, Chen J, Wang J, Wang M, Zhang Q, Zhang J, Zen K, Zhang CY. Exogenous plant MIR168a specifically targets mammalian LDLRAP1: evidence of cross-kingdom regulation by microRNA. Cell Res. 2012 Jan;22(1):107-26. doi: 10.1038/cr.2011.158. Epub 2011 Sep 20.

    PMID: 21931358BACKGROUND
  • Baier SR, Nguyen C, Xie F, Wood JR, Zempleni J. MicroRNAs are absorbed in biologically meaningful amounts from nutritionally relevant doses of cow milk and affect gene expression in peripheral blood mononuclear cells, HEK-293 kidney cell cultures, and mouse livers. J Nutr. 2014 Oct;144(10):1495-500. doi: 10.3945/jn.114.196436. Epub 2014 Aug 13.

    PMID: 25122645BACKGROUND
  • Yang J, Farmer LM, Agyekum AA, Elbaz-Younes I, Hirschi KD. Detection of an Abundant Plant-Based Small RNA in Healthy Consumers. PLoS One. 2015 Sep 3;10(9):e0137516. doi: 10.1371/journal.pone.0137516. eCollection 2015.

    PMID: 26335106BACKGROUND
  • Dickinson B, Zhang Y, Petrick JS, Heck G, Ivashuta S, Marshall WS. Lack of detectable oral bioavailability of plant microRNAs after feeding in mice. Nat Biotechnol. 2013 Nov;31(11):965-7. doi: 10.1038/nbt.2737. No abstract available.

    PMID: 24213763BACKGROUND
  • Snow JW, Hale AE, Isaacs SK, Baggish AL, Chan SY. Ineffective delivery of diet-derived microRNAs to recipient animal organisms. RNA Biol. 2013 Jul;10(7):1107-16. doi: 10.4161/rna.24909. Epub 2013 May 3.

    PMID: 23669076BACKGROUND
  • Witwer KW, McAlexander MA, Queen SE, Adams RJ. Real-time quantitative PCR and droplet digital PCR for plant miRNAs in mammalian blood provide little evidence for general uptake of dietary miRNAs: limited evidence for general uptake of dietary plant xenomiRs. RNA Biol. 2013 Jul;10(7):1080-6. doi: 10.4161/rna.25246. Epub 2013 Jun 3.

    PMID: 23770773BACKGROUND
  • Chan SY, Snow JW. Formidable challenges to the notion of biologically important roles for dietary small RNAs in ingesting mammals. Genes Nutr. 2017 Jul 7;12:13. doi: 10.1186/s12263-017-0561-7. eCollection 2017.

    PMID: 29308096BACKGROUND
  • Humphreys KJ, Conlon MA, Young GP, Topping DL, Hu Y, Winter JM, Bird AR, Cobiac L, Kennedy NA, Michael MZ, Le Leu RK. Dietary manipulation of oncogenic microRNA expression in human rectal mucosa: a randomized trial. Cancer Prev Res (Phila). 2014 Aug;7(8):786-95. doi: 10.1158/1940-6207.CAPR-14-0053.

    PMID: 25092886BACKGROUND
  • Papaioannou MD, Koufaris C, Gooderham NJ. The cooked meat-derived mammary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) elicits estrogenic-like microRNA responses in breast cancer cells. Toxicol Lett. 2014 Aug 17;229(1):9-16. doi: 10.1016/j.toxlet.2014.05.021. Epub 2014 May 28.

    PMID: 24877718BACKGROUND
  • Huggett JF, Foy CA, Benes V, Emslie K, Garson JA, Haynes R, Hellemans J, Kubista M, Mueller RD, Nolan T, Pfaffl MW, Shipley GL, Vandesompele J, Wittwer CT, Bustin SA. The digital MIQE guidelines: Minimum Information for Publication of Quantitative Digital PCR Experiments. Clin Chem. 2013 Jun;59(6):892-902. doi: 10.1373/clinchem.2013.206375. Epub 2013 Apr 9.

    PMID: 23570709BACKGROUND
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    PMID: 18546601BACKGROUND

Related Links

MeSH Terms

Interventions

Diet, Vegan

Intervention Hierarchy (Ancestors)

Diet, VegetarianDiet, Plant-BasedDiet TherapyNutrition TherapyTherapeuticsDietNutritional Physiological PhenomenaDiet, Food, and NutritionPhysiological Phenomena

Study Officials

  • Fermín Mar-Aguilar, Dr.

    Universidad Autonoma de Nuevo Leon

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Model Details: Baseline blood samples were obtained after 12 hours overnight fast; the postprandial miRNA state was measured after intake of a meal with beef (test meal) that consisted of 200 g roast beef with salad (lettuce, tomato, lentils) and a cup of rice. The control diet consisted of the same intervention, without the roast beef. Each intervention day the meals were prepared with fresh food. Participants ate meals under control of the study staff. Postprandial samples were collected at 2, 4 and 6 hours after the diet intervention. The subjects did not eat or drink again until the end of sample collection.
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

November 6, 2018

First Posted

November 14, 2018

Study Start

April 13, 2015

Primary Completion

November 16, 2015

Study Completion

May 22, 2016

Last Updated

November 15, 2018

Record last verified: 2018-11

Data Sharing

IPD Sharing
Will not share

Locations