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Nutritional Intervention Preconception and During Pregnancy to Maintain Healthy Glucose Metabolism and Offspring Health (NiPPeR)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02509988
Recruitment Status : Active, not recruiting
First Posted : July 28, 2015
Last Update Posted : May 24, 2019
Sponsor:
Collaborators:
National University Hospital, Singapore
Auckland UniServices Ltd.
Singapore Institute for Clinical Sciences
National University, Singapore
Nestec Ltd.
Information provided by (Responsible Party):
University of Southampton

Tracking Information
First Submitted Date  ICMJE July 16, 2015
First Posted Date  ICMJE July 28, 2015
Last Update Posted Date May 24, 2019
Actual Study Start Date  ICMJE July 2015
Actual Primary Completion Date October 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 17, 2018)
Glucose tolerance during pregnancy [ Time Frame: Pregnancy Oral Glucose Tolerance Test (OGTT) measurement at 24 - 32 weeks gestation ]
Original Primary Outcome Measures  ICMJE
 (submitted: July 27, 2015)
Glucose tolerance during pregnancy [ Time Frame: Pregnancy Oral Glucose Tolerance Test (OGTT) measurement at 28 weeks gestation ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 22, 2019)
  • Duration of gestation [ Time Frame: Up to 43 weeks, derived from estimated date of conception from menstrual and ultrasound scan data and date of delivery ]
  • Pregnancy weight gain and body composition [ Time Frame: Up to 36 weeks, between date of first pregnancy visit and late gestation ]
  • Postpartum weight retention and body composition [ Time Frame: Up to 2 years, between date of delivery and 6,12 and 24 months postpartum ]
  • Change in body composition before, during and after gestation [ Time Frame: Up to 4 years, between preconception, pregnancy and 2 years postpartum ]
  • Clinical pregnancy, pregnancy loss and live birth rates, including median time to conception of those who conceive during the treatment period and proportions conceiving within 3 months, 6 months and a year of commencing the NiPPeR drink [ Time Frame: Between recruitment and delivery ]
  • Gestational diabetes frequency [ Time Frame: Pregnancy OGTT measurement at 24 - 32 weeks gestation ]
  • Hypertensive disorders of pregnancy (pregnancy-induced hypertension and pre-eclampsia/eclampsia) [ Time Frame: Up to 49 weeks, between conception derived from estimated date of conception from menstrual and ultrasound scan data and date of delivery, and up to 6 weeks after delivery ]
  • Nausea and vomiting frequency [ Time Frame: Up to 36 weeks, between 7 weeks of gestation and delivery ]
  • Other antenatal, perinatal and postnatal complications [ Time Frame: Up to 49 weeks, between conception from estimated date of conception derived from menstrual and ultrasound scan data, and up to 6 weeks after delivery ]
  • Preconception and antenatal maternal wellbeing/mood (Edinburgh Post-natal Depression Scale and State-Trait Anxiety Inventory) [ Time Frame: Up to 2 years, between preconception and delivery ]
  • Postnatal maternal wellbeing/mood (Edinburgh Post-natal Depression Scale and State-Trait Anxiety Inventory) [ Time Frame: Up to 52 weeks, between date of delivery and infant age 1 year ]
  • Mode of labour onset and delivery [ Time Frame: Delivery ]
  • Neonatal complications and admission to neonatal care facilities [ Time Frame: Up to 4 weeks post-delivery ]
  • Preconception maternal micronutrient status (blood analysis) [ Time Frame: Date of second preconception visit up to 1 year before pregnancy ]
  • Antenatal maternal micronutrient status (blood analysis) [ Time Frame: Up to 30 weeks, between 7 weeks gestation and 37 weeks of gestation ]
  • Preconception maternal gut microbiota composition and activity profile (analysis of sequencing and transcription data) [ Time Frame: Up to 6 weeks from the start of intervention, date of preconception visit 2 which is up to 1 year before pregnancy ]
  • Antenatal and postnatal maternal gut and epithelial microbiota composition profile (analysis of sequencing data) [ Time Frame: Up to 18 months, between 7 weeks gestation and post-delivery visits ]
  • Maternal preconception biochemical, metabolic and molecular profiles [ Time Frame: Up to 6 weeks from the start of intervention, date of second preconception visit which is up to 1 year before pregnancy ]
  • Maternal antenatal biochemical, metabolic and molecular profiles [ Time Frame: Up to 30 weeks, between 7 weeks gestation and 37 weeks of gestation ]
  • Placental and cord tissue, and their cellular derivatives: biochemical, metabolic and molecular profiles [ Time Frame: Birth ]
  • Maternal postnatal biochemical, metabolic and molecular profiles [ Time Frame: 6 months after delivery ]
  • Maternal preconception epigenetic profile [ Time Frame: Preconception to up to 1 year before pregnancy ]
  • Maternal antenatal epigenetic profile [ Time Frame: Up to 30 weeks, between 7 weeks gestation and 37 weeks of gestation ]
  • Maternal postnatal epigenetic profile [ Time Frame: 6 months after delivery ]
  • Breast milk macronutrient profile (subsample) [ Time Frame: Up to 1 year, between date of delivery and 1 year postpartum ]
  • Breast milk micronutrient profile (subsample) [ Time Frame: Up to 1 year, between date of delivery and 1 year postpartum ]
  • Breast milk immune factor profile (subsample) [ Time Frame: Up to 1 year, between date of delivery and 1 year postpartum ]
  • Breast milk epigenetic profile (subsample) [ Time Frame: Up to 1 year, between date of delivery and 1 year postpartum ]
  • Breast milk biochemical, metabolic, microbiome and molecular profiles (subsample) [ Time Frame: Up to 1 year, between date of delivery and 1 year postpartum ]
  • Healthy lactogenesis [ Time Frame: Up to 1 year, between date of delivery and 1 year postpartum ]
  • Maternal and infant transcriptomics (including of breastmilk) [ Time Frame: Up to 34 months, between preconception, pregnancy and 1 year postpartum ]
  • Intrauterine growth and wellbeing as assessed by antenatal serial ultrasound scans [ Time Frame: Up to 30 weeks, between 7 weeks gestation and 37 weeks of gestation ]
  • Offspring birthweight and size at birth [ Time Frame: At birth ]
  • Offspring size for gestational age at birth, less than the 10th, 10th - 90th, and above the 90th percentiles for gestational age [ Time Frame: At birth ]
  • Offspring size for gestational age and sex at birth (percentile and standard deviation scores) [ Time Frame: At birth ]
  • Offspring adiposity (skinfold thicknesses, regional, total and percentage fat mass) [ Time Frame: Up to 2 years, between date of delivery and 2 years postpartum ]
  • Adiposity gain, body composition and linear growth during infancy and childhood [ Time Frame: Up to 2 years, from birth to infant age 2 years ]
  • Cord blood C-peptide [ Time Frame: At delivery ]
  • Offspring cardiometabolic profile [ Time Frame: Up to 2 years, from birth to infant age 2 years ]
  • Offspring allergic wellbeing [ Time Frame: Up to 2 years, from birth to infant age 2 years ]
  • Offspring biochemical, metabolic and molecular profiles [ Time Frame: Up to 2 years, from birth to infant age 2 years ]
  • Offspring epigenetic profile [ Time Frame: Up to 2 years, from birth to infant age 2 years ]
  • Infant gut microbiota composition and activity [ Time Frame: Up to 2 years, from birth to infant age 2 years ]
  • Influence of parental and offspring genotype, sociodemography, body composition, metabolism, lifestyle and diet on the above primary and secondary outcomes at baseline and with the intervention [ Time Frame: Up to 4 years, between preconception, pregnancy and 2 years postpartum ]
Original Secondary Outcome Measures  ICMJE
 (submitted: July 27, 2015)
  • Duration of gestation [ Time Frame: Up to 43 weeks, between date of last menstrual period and date of delivery ]
  • Pregnancy weight gain [ Time Frame: Up to 95 weeks, between date of preconception visit and date of delivery ]
  • Gestational diabetes frequency [ Time Frame: Pregnancy OGTT measurement at 28 weeks gestation ]
  • Nausea and vomiting frequency [ Time Frame: Up to 12 weeks, between 7 and 19 weeks gestation ]
  • Antenatal maternal wellbeing/mood (Edinburgh Post-natal Depression Scale and State-Trait Anxiety Inventory) [ Time Frame: Up to 30 weeks, between 7 weeks gestation and 37 weeks of gestation ]
  • Postnatal maternal wellbeing/mood (Edinburgh Post-natal Depression Scale and State-Trait Anxiety Inventory) [ Time Frame: Up to 52 weeks, between date of delivery and infant age 1 year ]
  • Mode of delivery [ Time Frame: Delivery ]
  • Preconception maternal micronutrient status (blood analysis) [ Time Frame: Date of second preconception visit up to 1 year before pregnancy ]
  • Antenatal maternal micronutrient status (blood analysis) [ Time Frame: Up to 30 weeks, between 7 weeks gestation and 37 weeks of gestation ]
  • Preconception maternal gut microbiota composition profile (analysis of sequencing data) [ Time Frame: Up to 6 weeks from the start of intervention, date of preconception visit 2 which is up to 1 year before pregnancy ]
  • Antenatal maternal gut microbiota composition profile (analysis of sequencing data) [ Time Frame: Up to 36 weeks, between 7 weeks gestation and date of delivery ]
  • Maternal preconception metabolomic profile [ Time Frame: Up to 6 weeks from the start of intervention, date of second preconception visit which is up to 1 year before pregnancy ]
  • Maternal antenatal metabolomic profile [ Time Frame: Up to 30 weeks, between 7 weeks gestation and 37 weeks of gestation ]
  • Maternal postnatal metabolomic profile [ Time Frame: 6 months after delivery ]
  • Maternal preconception epigenetic profile [ Time Frame: Second preconception visit up to 1 year before pregnancy ]
  • Maternal antenatal epigenetic profile [ Time Frame: Up to 30 weeks, between 7 weeks gestation and 37 weeks of gestation ]
  • Maternal postnatal epigenetic profile [ Time Frame: 6 months after delivery ]
  • Breast milk macronutrient profile (subsample) [ Time Frame: Up to 3 months, between date of delivery and 3 months postpartum ]
  • Breast milk micronutrient profile (subsample) [ Time Frame: Up to 3 months, between date of delivery and 3 months postpartum ]
  • Breast milk immune factor profile (subsample) [ Time Frame: Up to 3 months, between date of delivery and 3 months postpartum ]
  • Breast milk epigenetic profile (subsample) [ Time Frame: Up to 3 months, between date of delivery and 3 months postpartum ]
  • Breast milk metabolomic profile (subsample) [ Time Frame: Up to 3 months, between date of delivery and 3 months postpartum ]
  • Healthy lactogenesis (onset of lactation) [ Time Frame: Up to 3 months, between date of delivery and 3 months postpartum ]
  • Offspring birthweight 2,500-4,000 g [ Time Frame: At birth ]
  • Offspring size for gestational age size at birth (birthweight 10th-90th percentile for gestational age) [ Time Frame: At birth ]
  • Offspring size for gestational age size at birth (customised birthweight centile 10th-90th centile) [ Time Frame: At birth ]
  • Offspring adiposity (skinfold thicknesses, total and percentage fat mass) [ Time Frame: Up to 6 weeks, from date of birth to 6 weeks ]
  • Adiposity gain during infancy [ Time Frame: Up to 52 weeks, from birth to infant age 12 months ]
  • Cord blood C-peptide [ Time Frame: At delivery ]
  • Offspring healthy cardiometabolic risk factor profile [ Time Frame: Up to 52 weeks, from birth to infant age 12 months ]
  • Offspring allergic wellbeing (absence of allergic symptoms) [ Time Frame: Up to 52 weeks, from birth to infant age 12 months ]
  • Offspring metabolomic profile related to metabolic health [ Time Frame: Up to 52 weeks, from birth to infant age 12 months ]
  • Offspring metabolomic profile related to allergy [ Time Frame: Up to 52 weeks, from birth to infant age 12 months ]
  • Offspring epigenetic profile related to metabolic health [ Time Frame: Up to 52 weeks, from birth to infant age 12 months ]
  • Offspring epigenetic profile related to allergy [ Time Frame: Up to 52 weeks, from birth to infant age 12 months ]
  • Infant gut microbiota composition [ Time Frame: Up to 52 weeks, from birth to infant age 12 months ]
Current Other Pre-specified Outcome Measures
 (submitted: January 9, 2019)
  • Health economics analysis (cost benefit analysis) [ Time Frame: Composite analysis between preconception visit which is up to 1 year before pregnancy and infant age 2 years, assessed up to 4 years ]
  • Offspring neurocognitive and behavioural development (behavioural and Ages & Stages questionnaires) [ Time Frame: Up to 2 years, from birth to infant age 2 years ]
  • Offspring respiratory development (absence of respiratory symptoms) [ Time Frame: Up to 2 years, from birth to infant age 2 years ]
  • Offspring allergic development (clinical evaluation of atopic disorders and skin prick test reaction diameter) [ Time Frame: Up to 2 years, from birth to infant age 2 years ]
  • Offspring health and wellbeing (questionnaires) [ Time Frame: Up to 2 years, from birth to infant age 2 years ]
  • Maternal health and wellbeing [ Time Frame: Up to 4 years, between preconception visit which is up to 1 year before pregnancy and up to 2 years after delivery ]
Original Other Pre-specified Outcome Measures
 (submitted: July 27, 2015)
  • Health economics analysis (Quality - Adjusted Life Years) [ Time Frame: Composite analysis between preconception visit which is up to 1 year before pregnancy and infant age 12 months, assessed up to 34 months ]
  • Offspring neurocognitive development (relational binding analysis) [ Time Frame: Up to 52 weeks, from birth to infant age 12 months ]
  • Offspring respiratory development (absence of respiratory symptoms) [ Time Frame: Up to 52 weeks, from birth to infant age 12 months ]
  • Offspring allergic development (skin prick test reaction diameter) [ Time Frame: Up to 52 weeks, from birth to infant age 12 months ]
 
Descriptive Information
Brief Title  ICMJE Nutritional Intervention Preconception and During Pregnancy to Maintain Healthy Glucose Metabolism and Offspring Health
Official Title  ICMJE Nutritional Intervention Preconception and During Pregnancy to Maintain Healthy Glucose Metabolism and Offspring Health "(NiPPeR)"
Brief Summary The study aims to assess whether a nutritional drink taken before conception and continuing through pregnancy, assists in the maintenance of healthy glucose metabolism in the mother and promotes offspring health.
Detailed Description

It is known that maternal insulin resistance and high blood glucose levels in early pregnancy alter the functioning of the placenta in ways that persistently affect the supply of nutrients and fat in the unborn baby. There is an increasing focus on the need to optimise preconception nutrition but as yet, limited preconception interventions that are recognized as promoting health for the mother and her child.

The Investigators will recruit up to 1800 women, aged 18-38 years, who are planning a pregnancy in the United Kingdom, Singapore and New Zealand with the aim of securing 600 or more pregnancies. The participants will be randomly allocated to receive the standard nutritional drink or the study nutritional drink. Women who conceive between one and twelve months after starting the nutritional drink will be followed through pregnancy and studied with their babies for two years after delivery. Various testing will be carried out at relevant time points. Mothers will undergo blood, urine, hair and cheek swab sampling, dual-energy X-ray absorptiometry (DXA) scans along with body measurements and health and lifestyle questionnaires. Infants will undergo hair, cheek swab, urine and stool sampling along with body measurements, measurements of body composition and a DXA scan. Placental, cord and other perinatal tissues/samples will be collected.

The data collected will allow identification of the contributions of nutritional and lifestyle factors, social and economic status, ethnicity, genetics and metabolomics and gut microbes to maintaining healthy glucose metabolism in pregnancy, enhancing fertility, mood and reproductive outcomes in the mother, and promoting healthy growth, body composition and wellbeing in the children.

The effect of the intervention on the primary outcome will be examined in two special interest groups; i) women who are overweight or obese prior to conception & ii) women with documented evidence of dysglycemia prior to conception.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Other
Condition  ICMJE Hyperglycemia
Intervention  ICMJE
  • Dietary Supplement: Study nutritional drink
    Study nutritional drink containing a mix of micronutrients, probiotics and myo-inositol.
  • Dietary Supplement: Standard nutritional drink
    Standard nutritional drink containing a mix of micronutrients.
Study Arms  ICMJE
  • Experimental: Intervention (study nutritional drink)

    Study nutritional drink comes in the form of a sachet to mix with water & take twice a day (once in the morning and once in the evening).

    The drink will be taken before the participant becomes pregnant (for up to 1 year) and throughout pregnancy.

    Intervention: Dietary Supplement: Study nutritional drink
  • Active Comparator: Control (standard nutritional drink)

    Standard nutritional drink comes in the form of a sachet to mix with water & take twice a day (once in the morning and once in the evening).

    The drink will be taken before the participant becomes pregnant (for up to 1 year) and throughout pregnancy.

    Intervention: Dietary Supplement: Standard nutritional drink
Publications * Godfrey KM, Cutfield W, Chan SY, Baker PN, Chong YS; NiPPeR Study Group. Nutritional Intervention Preconception and During Pregnancy to Maintain Healthy Glucose Metabolism and Offspring Health ("NiPPeR"): study protocol for a randomised controlled trial. Trials. 2017 Mar 20;18(1):131. doi: 10.1186/s13063-017-1875-x.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: January 9, 2019)
1729
Original Estimated Enrollment  ICMJE
 (submitted: July 27, 2015)
1800
Estimated Study Completion Date  ICMJE March 2021
Actual Primary Completion Date October 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Women aged 18-38 years
  • Planning to conceive within 6 months
  • Able to provide written, informed consent
  • In Singapore: Chinese, Malay and Indian ethnicity or mixed Chinese/Malay/Indian ethnicity

Exclusion Criteria:

  • Pregnant or lactating at recruitment
  • Assisted fertility, apart from those taking clomiphene or letrozole alone
  • Pre-existing diabetes (type 1 or type 2)
  • Oral or implanted contraception currently or in the last month, or with an Intrauterine Contraceptive Device (IUCD) in situ
  • On metformin or systemic steroids currently or in the last month
  • Known serious food allergy
  • Not able to give informed consent
  • Women on anticonvulsants (who are treated with high dose B vitamins in pregnancy) currently or in the last month
  • On treatment for Human Immunodeficiency Virus (HIV), Hepatitis B or C currently or in the last month

The partners of the women (over 16 years of age) will also be invited to participate in the study. After having gained written informed consent, fathers will have blood, urine, hair sampling, cheek swabs and body measurements taken and will complete a health and a lifestyle questionnaire at one of the visits during pregnancy.

The mother will consent for their babies to have body measurements, buccal, hair, stool samples and allergy testing from birth to 24 months.

Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 38 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE New Zealand,   Singapore,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02509988
Other Study ID Numbers  ICMJE 13597
34104 ( Other Identifier: Auckland UniServices Ltd. )
2015/00205 ( Other Identifier: National University Hospital Singapore )
U1111-1171-8056 ( Other Identifier: Universal Trial Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Southampton
Study Sponsor  ICMJE University of Southampton
Collaborators  ICMJE
  • National University Hospital, Singapore
  • Auckland UniServices Ltd.
  • Singapore Institute for Clinical Sciences
  • National University, Singapore
  • Nestec Ltd.
Investigators  ICMJE
Principal Investigator: Wayne Cutfield, BHB MB ChB DCH MD FRACP The University of Auckland
Principal Investigator: Shiao-Yng Chan, MBBChir (UK), FRCOG (UK), PhD National University Hospital, Singapore
Principal Investigator: Keith Godfrey, BM PhD FRCP MRC Lifecourse Epidemiology Unit, University of Southampton
PRS Account University of Southampton
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP