Aberrant DNA MethylationMDEGNCT01811641
Methyl-Donors and EpiGenetics in The Gambia
An observational study of Aberrant DNA Methylation, run by Medical Research Council.
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. Read more about this study
- Who is it for?
- Ages 1 day to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Aberrant DNA Methylation
- What is being tested?
- season, dietary intake
- How many people
- 166 participants
- Where
- No sites listed yet
- Study dates
- Jan 2009to Dec 2015
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 day to 45 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Study population: women of reproductive age in rural Gambia and their infants
Who may be able to join
- women aged 18-45 years on 15th March 2009, resident in West Kiang
- born to the above women
Who cannot join
- 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
- those known to be severely malnourished (weight-for-height Z-score < -3)
About this study
Official title: Epigenesis in Humans: Can Maternal Methyl-donor-deficient Diets Induce Epigenetic Alterations in Their Offspring?
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.
- Conditions
- Aberrant DNA Methylation
- Being tested
- season, dietary intake
- Keywords
- season of conception, maternal nutritional status, infant DNA methylation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
season, dietary intakeOther
| Study group | Role | What they receive |
|---|---|---|
| maternal methyl-donors, infant epigenetics | women of reproductive age in rural Gambia, infants born to these women Receives: Other: season, dietary intake |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: infants: at 3-6 months of age
Secondary outcomes (1)
Blood biomarker status of women
Measurement of blood biomarkers monthly after dietary assessment or in early pregnancy
Measured: monthly for 12 months or in early pregnancy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Mar 2013 (estimated)
- Study startJan 2009
- Primary completionJun 2012
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Aberrant DNA MethylationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 166 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical Research Council
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Matt Silver, Medical Research Council
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01811641
- Sponsor's protocol ID
- MRC-ING-MDEG
- Acronym
- MDEG
- Status last verified
- Mar 2016
- First submitted
- 11 Mar 2013
- Last updated
- 22 Mar 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 24781383Silver 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(1):118. doi: 10.1186/s13059-015-0660-y.
PubMed 26062908Dominguez-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.
PubMed 23576045
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Epigenesis in Humans: Can Maternal Methyl-donor-deficient Diets Induce Epigenetic Alterations in Their Offspring?
- ClinicalTrials.gov ID
- NCT01811641
- Acronym / sponsor ID
- MDEG / MRC-ING-MDEG
- Conditions
- Aberrant DNA Methylation
- Keywords
- season of conception, maternal nutritional status, infant DNA methylation
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 166 participants (actual)
- Lead sponsor
- Medical Research CouncilOther government
- Study start
- Jan 2009
- Primary completion
- Jun 2012 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 14 Mar 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| maternal methyl-donors, infant epigenetics | – | Other: season, dietary intakewomen of reproductive age in rural Gambia, infants born to these women |
Who may qualify
- Ages
- 1 day to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
- Study population
- women of reproductive age in rural Gambia and their infants
Key inclusion criteria (2 listed)
- women aged 18-45 years on 15th March 2009, resident in West Kiang
- born to the above women
Key exclusion criteria (5 listed)
- 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
- those known to be severely malnourished (weight-for-height Z-score < -3)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| season, dietary intake | Other | maternal methyl-donors, infant epigenetics |
Primary outcome
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
1 secondary outcome
Blood biomarker status of women
Time frame: monthly for 12 months or in early pregnancy
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2016.
- Results publication: PubMed 24781383Dominguez-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.
- Results publication: PubMed 26062908Silver 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(1):118. doi: 10.1186/s13059-015-0660-y.
- Derived from this study: PubMed 23576045Dominguez-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.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
An observational study of Aberrant DNA Methylation, run by Medical Research Council.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
DNA methylation of infants (time frame: infants: at 3-6 months of age). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01811641, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Mar 2016.