Plain English Summary
Background and study aims
Pre-eclampsia (condition causing high blood pressure and significant amounts of protein in the urine) is a major complication of pregnancy which can adversely affect mother and baby. At present there is no treatment except ending the pregnancy, which is difficult to do when babies are very premature. Selenium is an essential mineral of all diets. We have evidence that more than a small proportion of people living in the UK are partially deficient in selenium. Those who are young women are more liable to get pre-eclampsia when they get pregnant. In this pilot study we are testing the effect of small supplements of selenium to bring the daily intake to the recommended daily intake during pregnancy. We are asking 200 volunteers in their first pregnancies to enter a trial: half the women receive the daily supplement and the other half get a dummy tablet. Blood and other tests taken through pregnancy are designed to show whether or not the response to receiving the supplement changes the test results in a direction that favours not getting pre-eclampsia. If this is so, a much bigger study would be justified, which might lead to reasonable reduction in the disorder by a simple and safe dietary supplement.
Who can participate?
Women who are 12-14 weeks pregnant with their first baby visiting the John Radcliffe Hospital for a 12-week pregnancy scan will be approached to see if they wish to enter the trial. They are not eligible if under 18 years old, current smokers, taking any supplement containing selenium, taking thyroid medication, multiple pregnancy, abnormal ultrasound scan, chronic protein in the urine, heparin treatment, HIV, Hepatitis-B or Hepatitis-C positive, yeast intolerance (supplement contains yeast), inability or refusal to give informed consent.
What does the study involve?
The study will have two treatment groups: 60 mcg/day of selenium as selenium-enriched yeast or placebo (dummy) yeast (60 mcg/day is the recommended intake for UK pregnant women). Women will be randomly allocated to either treatment. A blood sample will be taken from all recruits at trial entry. Some blood will be used to measure selenium concentration. The remainder will be banked, along with a urine sample for later analysis. If separate, explicit, consent has been given for a blood sample for genetic analysis, an additional 5 ml of blood will be taken as part of the same procedure. Information will be recorded by the trial midwife to include:- blood pressure, date of last period, weight, height, ethnicity, family history of pre-eclampsia, chronic illness e.g. chronic hypertension, diabetes, thyroid disease, current medication, presence of severe morning sickness, smoker/non-smoker, alcohol use, vegetarian or not. Women will be given a simple food frequency questionnaire to complete and a further questionnaire about dietary supplements taken which may be filled in at home. At week 20, women will again attend the John Radcliffe Hospital for a scan and at 34-36 weeks, they will be seen by the research midwife either at the hospital or at their homes. Blood and urine samples will be taken at 20 and 35 weeks and banked for measurement of different components that may be related to the risk of pre-eclampsia.
What are the possible benefits and risks of participating?
There is no benefit to the woman herself from enrolling but her participation may help women in the future to have a lower risk of pre-eclampsia as a result of what the study shows. The dose of selenium given is a nutritional dose and is the recommended intake of selenium for women. There are no risks of supplementation with selenium at this level. Women in many countries have a considerably higher intake than this.
Where is the study run from?
The study is run from the University of Surrey but women are recruited and followed up at the John Radcliffe Hospital in Oxford, a known centre of excellence for pre-eclampsia.
When is the study starting and how long is it expected to run for?
The study started on 16 February 2009 and recruited up until July 2011. Analysis of the information gathered from the trial is still ongoing.
Who is funding the study?
The Wellcome Trust (UK).
Who is the main contact?
Professor Margaret Rayman
m.rayman@surrey.ac.uk
Trial website
Contact information
Type
Scientific
Primary contact
Prof Margaret Rayman
ORCID ID
Contact details
Faculty of Health and Medical Sciences
University of Surrey
Guildford
GU2 7XH
United Kingdom
-
m.rayman@surrey.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
SPRINT version 5
Study information
Scientific title
Selenium in PRegnancy INTervention: a double-blind, randomised, placebo-controlled, two-group study
Acronym
SPRINT
Study hypothesis
A small increase in selenium (Se) intake in pregnant women of inadequate Se status will protect against:- pre-eclampsia risk (as assessed by biomarkers), inflammation, oxidative stress, endothelial activation and placental dysfunction by increasing Se status and selenoprotein concentration.
Ethics approval
Milton Keynes REC, 11/12/2008, ref no 08/H0603/46
Study design
Double-blind randomised placebo-controlled two-group study
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Prevention
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Pre-eclampsia
Intervention
Two treatment groups: 60 mcg/day of selenium as selenium-enriched yeast or placebo yeast (60 mcg/day is the recommended intake for UK pregnant women).
Total duration of intervention: From randomisation (at 12 - 14 weeks gestation) until delivery.
Intervention type
Supplement
Phase
Not Applicable
Drug names
Selenium supplement
Primary outcome measures
Plasma soluble fms-like tyrosine kinase-1 (sFlt-1) concentration. Measured in samples taken at 35 weeks gestation.
Secondary outcome measures
Plasma concentrations of: placental growth factor (PlGF), sEndoglin, ActivinA, InhibinA, E-selectin, vascular cell adhesion molecule 1 (VCAM-1), 3-Nitrotyrosine, Pentraxin 3, C-reactive protein (CRP). Measured in samples taken at 35 weeks gestation.
Overall trial start date
16/02/2009
Overall trial end date
15/02/2014
Reason abandoned
Eligibility
Participant inclusion criteria
1. First pregnancy
2. 12-14 weeks pregnant at randomisation
Participant type
Patient
Age group
Adult
Gender
Female
Target number of participants
200 (230 recruited to allow drop-out rate of 15%)
Participant exclusion criteria
1. Under 18 years old
2. Current smokers (who have lower risk of pre-eclampsia)
3. Taking any supplement containing Se
4. Taking thyroid medication
5. Multiple pregnancy
6. Abnormal fetal anomaly scan
7. Chronic proteinuria
8. Heparin treatment
9. Human immunodeficiency virus (HIV), Hep-B or Hep-C positive
10. Yeast intolerance (supplement contains yeast)#
11. inability or refusal to give informed consent (the genetic component of the trial will be omitted in those who do not give explicit consent to this aspect of the trial)
Recruitment start date
16/02/2009
Recruitment end date
01/07/2011
Locations
Countries of recruitment
United Kingdom
Trial participating centre
University of Surrey
Guildford
GU2 7XH
United Kingdom
Sponsor information
Organisation
University of Surrey (UK)
Sponsor details
Stag Hill
Guildford
GU2 7XH
United Kingdom
-
k.robson@surrey.ac.uk
Sponsor type
University/education
Website
Funders
Funder type
Charity
Funder name
Wellcome Trust (UK) grant ref: 083918/Z/07/Z
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary
2014 results in http://www.ncbi.nlm.nih.gov/pubmed/24708917
2015 results in http://www.ncbi.nlm.nih.gov/pubmed/25948667
2015 results in http://www.ncbi.nlm.nih.gov/pubmed/26675765
Publication citations
-
Results
Rayman MP, Searle E, Kelly L, Johnsen S, Bodman-Smith K, Bath SC, Mao J, Redman CW, Effect of selenium on markers of risk of pre-eclampsia in UK pregnant women: a randomised, controlled pilot trial., Br. J. Nutr., 2014, 112, 1, 99-111, doi: 10.1017/S0007114514000531.
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Results
SC Bath, VL Furmidge-Owen, CWG Redman, MP Rayman, Gestational changes in iodine status in a cohort study of pregnant women from the United Kingdom: season as an effect modifier, Am J Clin Nutr, 2015 , doi: 10.3945/ajcn.114.105536 .