Methyl-Donors and EpiGenetics in The Gambia

Aberrant DNA Methylation Clinical Trial

— MDEG  

Official title:

Epigenesis in Humans: Can Maternal Methyl-donor-deficient Diets Induce Epigenetic Alterations in Their Offspring?

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01811641
• Other study ID #: MRC-ING-MDEG
• Status: Completed
• Phase: N/A
• First received: March 11, 2013
• Last updated: March 21, 2016
• Start date: January 2009
• Est. completion date: December 2015

Study information

• Verified date: March 2016
• Source: Medical Research Council
• Contact: n/a
• Is FDA regulated: No
• Health authority: Gambia: MRC Ethics Committee
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 166
• Est. completion date: December 2015
• Est. primary completion date: June 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: N/A to 45 Years

Eligibility

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)

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Aberrant DNA Methylation

Intervention

Other:
• season, dietary intake

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Medical Research Council

References & Publications (2)

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 metastabl — View Citation

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	DNA methylation of infants	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	infants: at 3-6 months of age	No
Secondary	Blood biomarker status of women	Measurement of blood biomarkers monthly after dietary assessment or in early pregnancy	monthly for 12 months or in early pregnancy	No