Epigenetic Analysis of Malnutrition

The PROVIDE study (Dhaka, Bangladesh) is a randomized clinical trial platform which evaluated the efficacy of delayed-dose oral rotavirus vaccine as well as the benefit of an injectable polio vaccine replacing one dose of oral polio vaccine. This rigorous infrastructure supported the additional examination of hypotheses of vaccine underperformance. Primary and secondary efficacy and immunogenicity measures for rotavirus and polio vaccines were measured, as well as the impact of maternal and childhood malnutrition, environmental enteropathy, and additional exploratory variables.

This study has been conducted to test the role of epigenetics in malnutrition, specifically the genome-wide role of histone modifications, which are known to provide a precise signature of metabolic state and immune system function.

• Study Design:
  • Clinical Trial
• Study Type:
  • Interventional
  • Randomized
  • Clinical Trial
• Total number of consented subjects: 59
• Subject Sample Telemetry Report (SSTR)

Criteria for the PROVIDE Study are as follows:

• Mother willing to sign informed consent form.
• Healthy infant aged 0 to 7 days old.
• No obvious congenital abnormalities or birth defects.
• No abnormal (frequency and consistency) stools since birth.
• Stable household with no plans to leave the area for the next one year.

• Parents are not willing to have child vaccinated at the field clinic.
• Parents are not willing to have child's blood drawn.
• Parents are planning to enroll child into another clinical study during the time period of this trial.
• Mother not willing to have blood drawn and breast milk extracted.
• Parents not willing to have field research assistant in home two times per week.
• History of seizures or other apparent neurologic disorders.
• Infant received any vaccines before start of study, except Bacillus Calmette-Guerin (BCG).
• Infant has any sibling currently or previously enrolled in this study, including a twin.

Criteria for the Epigenetic Analysis of Malnutrition study include meeting the inclusion criteria for the PROVIDE study and either being stunted (a height for age Z score of 2 standard deviations under the WHO's mean) or of normal height for age. These criteria were chosen so that meaningful differences in H3K4me3 expression could be detected between malnourished and well-nourished participants.

PROVIDE Study start date: May 2011

PROVIDE Study completion date: November 2014

PROVIDE Primary completion date: October 2014

Epigenetic Analysis of Malnutrition Study high throughput sequencing start date: 2013

Epigenetic Analysis of Malnutrition Study sequencing end date: 2014

• Primary Phenotype: Stunting
• Growth Disorders
• Malnutrition
• Epigenomics
• Virus Diseases
• Parasitic Diseases
• Digestive System Diseases
• Respiratory Tract Diseases
• Nervous System Diseases
• Nutritional and Metabolic Diseases
• Immune System Diseases
• Disorders of Environmental Origin

• PubMed
• BioSample
• MeSH

• Co-Investigators
  • David Auble, Ph.D. Department of Biochemistry and Molecular Genetics, University of Virginia Health System, Charlottesville, VA, USA.
  • William Petri, M.D., Ph.D. Division of Infectious Diseases and International Health, University of Virginia Health Systema, Charlottesville, VA, USA.
  • Rashidul Haque, M.B., Ph.D. International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh.
• Funding Source for Sequencing
  • Gift from the Manning Family Foundation. Charlottesville, VA, USA.
• Funding Source for Study Samples
  • PROVIDE OPP1017093. Bill and Melinda Gates Foundation, Seattle, WA, USA.