Investigating hormones triggering the onset of sustained lactation

ISRCTN	ISRCTN12667795
DOI	https://doi.org/10.1186/ISRCTN12667795
ClinicalTrials.gov (NCT)	Nil known
Clinical Trials Information System (CTIS)	Nil known
Integrated Research Application System (IRAS)	278264
Protocol serial number	IRAS 278264, PID 14930
Sponsor	University of Oxford
Funder	Family Larsson‐Rosenquist Foundation

Submission date: 28/06/2021
Registration date: 07/07/2021
Last edited: 02/10/2023

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Pregnancy and Childbirth

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims
Breastfeeding is controlled by hormones that trigger the start of milk secretion (known as secretory activation) within the first few days after giving birth. Delayed secretory activation is a major cause of breastfeeding failure. However, the hormone levels required for secretory activation and successful breastfeeding are unknown. The INSIGHT pilot study will assess the feasibility of collecting maternal blood samples for hormone measurements within the first days after giving birth and the main INSIGHT study will establish the reference intervals for hormone levels in the blood during the first 4 days after giving birth.

Who can participate?
Pregnant women aged 18 and over who are intending to breastfeed

What does the study involve?
The researchers will take a blood sample during the third trimester, and then collect blood samples before and after a breastfeed on each of the first 4 days after giving birth. They would also like to obtain a urine and breast milk sample on day 4 after giving birth. Each participant will be asked to keep a diary of when her milk comes in.

Where is the study run from?
The Women's Centre at the John Radcliffe Hospital (UK)

When is the study starting and how long is it expected to run for?
March 2020 to July 2024

Who is funding the study?
The Family Larsson-Rosenquist Foundation (Switzerland)

Who is the main contact?
Prof. Fadil Hannan
fadil.hannan@wrh.ox.ac.uk

Contact information

Prof Fadil Hannan
Scientific

Nuffield Department of Women's and Reproductive Health
University of Oxford
Level 4, Women's Centre
John Radcliffe Hospital
Headley Way
Headington
Oxford
OX3 9DU
United Kingdom

ORCID ID	0000-0002-2975-5170
Phone	+44 (0)1865 222937
Email	fadil.hannan@wrh.ox.ac.uk

Study information

Primary study design	Observational
Study design	Observational study with an internal pilot feasibility study
Secondary study design	Cohort study
Participant information sheet	ISRCTN12667795_PIS_V1.0_28Apr21.docx
Scientific title	Investigating hormones triggering the onset of sustained lactation
Study acronym	INSIGHT
Study objectives	Current study hypothesis as of 11/08/2022: Breastfeeding is a hormonally controlled process that is important for promoting infant growth and development and reducing the maternal risk of diseases such as diabetes and breast cancer. However, the hormone concentrations required to initiate lactation in the early postpartum period are unknown. The INSIGHT study involves an initial pilot phase to evaluate the feasibility of sample collection in the early postpartum period. The main study phase will characterise lactation hormone concentrations at the onset of copious milk secretion during the first 4 days post-partum. The INSIGHT study aims to establish reference intervals for hormones initiating lactation in the early postpartum period. Previous study hypothesis: Breastfeeding is a hormonally controlled process that is important for promoting infant growth and development and reducing the risk of diseases such as diabetes and breast cancer in the mother. This pilot observational study will evaluate the feasibility of sample collection in the early postpartum period for defining lactation hormone concentrations at the onset of copious milk secretion.
Ethics approval(s)	Approved 11/09/2020, East of England - Cambridgeshire and Hertfordshire Research Ethics Committee (The Old Chapel, Royal Standard Place, Nottingham, NG1 6FS, UK; +44 (0)207 104 8096, +44 (0)207 104 8106, +44 (0)207 104 8265; cambsandherts.rec@hra.nhs.uk), REC ref: 20/EE/0172
Health condition(s) or problem(s) studied	Breastfeeding
Intervention	Current intervention as of 10/08/2022: The INSIGHT study involves the following study procedures: Baseline (pregnancy): Blood sample collection on a single occasion during late pregnancy Postpartum: 1. Self-recording of breast fullness during postpartum days 1-4 2. Blood sample collection before and after a breastfeed on postpartum days 1-4 3. Spot urine sample collection on postpartum day 4 4. Breast milk collection on postpartum day 4 Previous intervention: The INSIGHT pilot study involves the following study procedures: Baseline (pregnancy): Blood sample collection on a single occasion during late pregnancy Postpartum: 1. Self-recording of breast fullness during postpartum days 1-4 2. Blood sample collection before and after a breastfeed on postpartum day 4 3. Spot urine sample collection on postpartum day 4 4. Breast milk collection on postpartum day 4
Intervention type	Other
Primary outcome measure(s)	Current primary outcome measure as of 10/08/2022: INSIGHT study: Serum hormone reference intervals established by parametric or non-parametric analysis during the first 4 days post-partum INSIGHT pilot study: Feasibility of postpartum sample collection: assessed using the proportion of participants willing to be recruited and provide samples on the 4th day postpartum Previous primary outcome measure: Feasibility of postpartum sample collection: assessed using the proportion of participants willing to be recruited and provide samples on the 4th day postpartum
Key secondary outcome measure(s)	Current secondary outcome measures as of 10/08/2022: INSIGHT study: The following outcomes will be measured using biochemical analysis during the first 4 days post-partum: 1. Longitudinal changes in serum lactation hormones 2. Associations between serum lactation hormones and maternal co-morbidities, medications, mode of delivery, or pregnancy complications 3. Serum lactation hormone concentrations correlated with timing of onset of milk production 4. Breast milk hormone composition 5. Serum lactation hormones correlated with breast milk volume. INSIGHT pilot study: 1. Lactation hormones measured by immunoassay in blood and urine samples on the 4th day postpartum 2. Breast milk hormones and bioactive molecules measured by immunoassay in breast milk samples on the 4th day postpartum Previous secondary outcome measures: 1. Lactation hormones measured by immunoassay in blood and urine samples on the 4th day postpartum 2. Breast milk hormones and bioactive molecules measured by immunoassay in breast milk samples on the 4th day postpartum
Completion date	31/12/2024

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Female
Target sample size at registration	1068
Key inclusion criteria	1. Pregnant women, aged ≥18 years 2. Term singleton pregnancy (≥37 weeks gestation) 3. Intention to fully or partially breastfeed 4. Willing and able to give informed consent for participation in the study
Key exclusion criteria	1. Severe maternal illness including diagnosis of postpartum depression or psychosis 2. Severe infant illness including major congenital abnormalities and infants who are only expected to live for a short period of time 3. Prolonged separation of infant from mother e.g. due to admission to the neonatal unit 4. Major COVID-19 symptoms e.g. pyrexia and continuous cough 5. Mother or infant infected with blood-borne viruses such as HIV 6. Resides outside of Oxfordshire 7. Safeguarding issues that may impede the safety of research staff carrying out home visits 8. Current participation in another research study that involves investigational medicinal products
Date of first enrolment	01/09/2021
Date of final enrolment	01/07/2024

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

Oxford University Hospitals NHS Foundation Trust

Headley Way
Headington
Oxford
OX3 9DU
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not expected to be made available
IPD sharing plan	The datasets generated during and/or analysed during the current study are not expected to be made available. The main aim of this pilot study is to assess the feasibility of participant recruitment and sample collection. Therefore, there may be little or no participant-level data. In addition, the consent form does not specify sharing of any participant-level data.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Protocol article		30/08/2022	31/08/2022	Yes	No
HRA research summary			28/06/2023	No	No
Participant information sheet	version V1.0	28/04/2021	08/07/2021	No	Yes
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Study website	Study website	11/11/2025	11/11/2025	No	Yes

Additional files

ISRCTN12667795_PIS_V1.0_28Apr21.docx: Uploaded 08/07/2021

Editorial Notes

02/10/2023: The contacts were updated.
12/09/2023: The following changes were made to the study record:
1. The target number of participants was changed from 100 to 1068.
2. The recruitment end date was changed from 01/09/2023 to 01/07/2024.
3. The overall study end date was changed from 01/07/2024 to 31/12/2024.
31/08/2022: Publication reference added.
11/08/2022: The following changes have been made:
1. The public title has been changed from "Investigating hormones triggering the onset of sustained lactation (pilot study to assess the feasibility of sample collection)" to "Investigating hormones triggering the onset of sustained lactation”.
2. The scientific title has been changed from "Investigating hormones triggering the onset of sustained lactation (pilot study)" to "Investigating hormones triggering the onset of sustained lactation”.
3. The study hypothesis has been updated.
4. The study design has been changed from "Pilot observational study" to "Observational study with an internal pilot feasibility study”.
5. The plain English summary has been updated.
10/08/2022: The following changes have been made:
1. The overall trial end date has been changed from 01/03/2024 to 01/07/2024 and the plain English summary has been updated to reflect this change.
2. The intervention has been updated.
3. The primary outcome measure has been updated.
4. The secondary outcome measures have been updated.
20/08/2021: Internal review.
08/07/2021: The participant information sheet has been uploaded.
29/06/2021: Trial's existence confirmed by the East of England - Cambridgeshire and Hertfordshire Research Ethics Committee.