Methyl-Donors and EpiGenetics in The Gambia (MDEG)

• ClinicalTrials.gov Identifier: NCT01811641
• Recruitment Status: Completed
• First Posted: March 14, 2013
• Last Update Posted: March 22, 2016
• Sponsor: Medical Research Council
• Information provided by (Responsible Party): Matt Silver, Medical Research Council

Study Description

Brief Summary:

Accumulating evidence suggests that early-life nutrition can affect metabolism and thus increase the risk of disease in adulthood (e.g. type II diabetes and obesity). One possible mechanism to explain these effects is epigenetic variation at critical periods of development. Epigenetic variation describes non-inherited permanent alterations to an individuals DNA.

Recent work in mouse models has demonstrated that maternal nutritional status can affect such epigenetic processes such as DNA methylation and gene expression during embryonic development, with profound effects on outcomes. The investigators aim to study these processes in humans for the first time. The investigators will exploit the "experiment of nature" setting in The Gambia, i.e. fluctuation in diet according to season. During the 'hungry' season diets are known to be depleted in nutrients required for epigenetic gene regulation. Nutritional biomarkers in blood as well as the dietary intake will be measured in pregnant women according to season. A blood sample will also be taken from babies born to these women to determine whether there is a direct effect of diet on mothers' nutritional status and hence variation in DNA methylation patterns in their babies by season.

Condition or disease	Intervention/treatment
Aberrant DNA Methylation	Other: season, dietary intake

Study Design

• Study Type: Observational
• Actual Enrollment: 166 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Epigenesis in Humans: Can Maternal Methyl-donor-deficient Diets Induce Epigenetic Alterations in Their Offspring?
• Study Start Date: January 2009
• Actual Primary Completion Date: June 2012
• Actual Study Completion Date: December 2015

Groups and Cohorts

Group/Cohort	Intervention/treatment
maternal methyl-donors, infant epigenetics; women of reproductive age in rural Gambia, infants born to these women	Other: season, dietary intake

Outcome Measures

Primary Outcome Measures :

1. DNA methylation of infants [ Time Frame: infants: at 3-6 months of age ]

   Measurement of DNA methylation of infants recruited into the study, at 3-6 months of age.

   Measurement of blood biomarkers monthly after dietary assessment or in early pregnancy

Secondary Outcome Measures :

1. Blood biomarker status of women [ Time Frame: monthly for 12 months or in early pregnancy ]
   Measurement of blood biomarkers monthly after dietary assessment or in early pregnancy

Biospecimen Retention:   Samples With DNA

blood, buccal swab, hair follicles

Eligibility Criteria

• Ages Eligible for Study: up to 45 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

women of reproductive age in rural Gambia and their infants

Criteria

Inclusion criteria women:

- women aged 18-45 years on 15th March 2009, resident in West Kiang

Exclusion criteria women:

• on contraception
• confirmed pregnancy at recruitment
• enrolment in any study other than the ENID (Early Nutrition and Immune Development) trial (ISRCTN49285450)
• suffering from severe anaemia (haemoglobin <7 g/dl) or known sickle cell disease

Inclusion criteria infants:

- born to the above women

Exclusion criteria infants:

- those known to be severely malnourished (weight-for-height Z-score < -3)

Contacts and Locations

No Contacts or Locations Provided

More Information

Publications of Results:

Dominguez-Salas P, Moore SE, Baker MS, Bergen AW, Cox SE, Dyer RA, Fulford AJ, Guan Y, Laritsky E, Silver MJ, Swan GE, Zeisel SH, Innis SM, Waterland RA, Prentice AM, Hennig BJ. Maternal nutrition at conception modulates DNA methylation of human metastable epialleles. Nat Commun. 2014 Apr 29;5:3746. doi: 10.1038/ncomms4746.

Silver MJ, Kessler NJ, Hennig BJ, Dominguez-Salas P, Laritsky E, Baker MS, Coarfa C, Hernandez-Vargas H, Castelino JM, Routledge MN, Gong YY, Herceg Z, Lee YS, Lee K, Moore SE, Fulford AJ, Prentice AM, Waterland RA. Independent genomewide screens identify the tumor suppressor VTRNA2-1 as a human epiallele responsive to periconceptional environment. Genome Biol. 2015 Jun 11;16:118. doi: 10.1186/s13059-015-0660-y.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Dominguez-Salas P, Moore SE, Cole D, da Costa KA, Cox SE, Dyer RA, Fulford AJ, Innis SM, Waterland RA, Zeisel SH, Prentice AM, Hennig BJ. DNA methylation potential: dietary intake and blood concentrations of one-carbon metabolites and cofactors in rural African women. Am J Clin Nutr. 2013 Jun;97(6):1217-27. doi: 10.3945/ajcn.112.048462. Epub 2013 Apr 10.

• Responsible Party: Matt Silver, MRC Senior Investigator Scientist, Medical Research Council
• ClinicalTrials.gov Identifier: NCT01811641
• Other Study ID Numbers: MRC-ING-MDEG
• First Posted: March 14, 2013
• Last Update Posted: March 22, 2016
• Last Verified: March 2016

Keywords provided by Matt Silver, Medical Research Council:

season of conception; maternal nutritional status; infant DNA methylation