LIFT-UP: Randomized Controlled Trial of Fortification of Human Milk (LIFT-UP RCT)

January 16, 2026 updated by: Katherine Semrau, Harvard School of Public Health (HSPH)

Low Birthweight and Preterm Infant Feeding Trial and Supportive Care Package (LIFT-UP): Randomized Controlled Trial of In-facility Fortification of Human Milk in India

The goal of the LIFT-UP randomized controlled trial is to evaluate the efficacy of feeding routinely and fortified human milk using a standardized clinical protocol to very low birthweight (VLBW) or very preterm (VPT) infants in the NICU compared to not feeding routinely fortified human milk using the standardized clinical protocol.

The primary research question is: Will VLBW or VPT infants in the NICU who are fed fortified human milk using a standardized feeding protocol have better growth outcomes by facility discharge and at 3 months of age, less illness by discharge, and decreased mortality by discharge and at one month compared to those who are not routinely fed fortified human milk using the same feeding protocol?

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

AIM: To improve feeding and growth outcomes among very low birthweight (LBW; ≤1.5kg) or very preterm (≤32 weeks gestational age) infants admitted to neonatal intensive care units (NICU) in India through fortification of human milk.

OBJECTIVE: To evaluate (via individually randomized controlled study) the efficacy of feeding routinely and fortified human milk using a standardized clinical protocol to very LBW or very preterm infants in the NICU compared to not feeding routinely fortified human milk using the standardized clinical protocol.

STUDY DESIGN This study is a multi-site individually randomized prospective trial among VLBW or VPT infants admitted to the NICU in study facilities who consume human milk and meet eligibility criteria (along with their mothers).

SCREENING AND ENROLLMENT All infants admitted to the NICU and their mothers will be screened for study eligibility. Screening will be performed within 24 hours of birth for inborn infants and within 48 hours of birth for outborn infants. Eligible dyads with the intention to feed human milk [mother's own milk (MOM) or pasteurized donor human milk (PDHM)] whose mothers provide consent will be enrolled into the study.

Once the mother-infant dyad is enrolled and prior to randomization, they will:

Receive the guideline-driven standard of care and be provided access to breast pumps to help initiate and advance breast milk feeding. The guideline-driven standard of care includes facility-based lactation support/feeding counseling + KMC + WASH components designed specifically for small vulnerable newborns and was developed as part of a different study protocol (see NCT06390943).

Adhere to a clinical guideline including targets for initiating and advancing breast milk feeding. Initially, this clinical guideline will help infants achieve breast milk volume intake of at least 60 mL/kg/day, the primary criterion for randomization. After randomization, the clinical guideline will continue to support advancing human milk feeding for all infants advance to 180 mL/kg/day.

RANDOMIZATION Once an infant consumes at least 60 mL/kg/day of breast milk, enrolled dyads will be assessed for eligibility for randomization. Eligible dyads will be randomized individually in a 1:1 ratio to either the intervention or comparison arm. Randomization sequences will be previously generated by the study statistician. If an infant does not consume at least 60 mL/kg/day of breastmilk by day 10 of chronological age, the mother-infant dyad will be administratively withdrawn from the study.

DELIVERY OF INTERVENTION Mothers of infants randomized to the intervention arm will express their breast milk into a standardized measurement cup (or PDHM can be used). Clinical research staff will mix human milk fortifier (HMF) in human milk (either MOM or PDHM, if available) per manufacturer specifications per feed for a minimum of 21 days.

Dyads in both arms will continue to receive the guideline-driven standard of care, access to breast pumps, and follow the volume target and trajectory protocol until they meet stopping criteria. Data will be collected every 24 hours, including a log at every feed, regardless of study arm assignment.

If an infant in either arm does not meet protocolized minimum volume targets or trajectories AND that infant meets weight-based safety net criteria, clinicians will intervene per judgment aligned with national and local protocols.

The intervention will not be continued once the infant meets stopping criteria with the goal of the infant having fully transitioned to exclusive breast milk feeding by then.

STOPPING CRITERIA After the minimum duration of 21 days post-randomization, hospitalized infants should continue to receive volume targeted feeding with or without HMF for as long as they receive expressed breast milk. Once infants transition to full, direct breastfeeding in preparation for discharge or are being discharged per clinician discretion, they will stop adhering to the volume targets and infants in the intervention group will stop receiving fortified human milk.

DISCHARGE FROM FACILITY TO HOME After stopping criteria are met, routine clinical care around infant feeding will be provided. Infants can be discharged home when deemed clinically appropriate per facility protocols and clinician judgment. The guideline-driven standard of care will encourage all mothers to exclusively breastfeed their infants prior to discharge and to continue doing so after discharge.

POST-DISCHARGE FACILITY VISITS All dyads will be followed up at 2 weeks of age, 4 weeks of age, and 3 months of chronological age.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
776

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • India
    • Karnataka
      • Ballary, Karnataka, India
        • Recruiting
        • Ballari Medical College and Research Centre
        • Contact:
          • Durgappa, MD
      • Belagavi, Karnataka, India
        • Not yet recruiting
        • KLES Dr Prabhakar Kore Hospital & Medical Research Center
        • Contact:
          • Roopa Bellad, MD
        • Principal Investigator:
          • Roopa Bellad, MD
        • Sub-Investigator:
          • Sunil S Vernekar
        • Sub-Investigator:
          • S M Dhaded
      • Davangere, Karnataka, India
        • Recruiting
        • JJM Medical College
        • Contact:
          • Gowdar Guruprasad, MD, DCH, DNB, DM
    • Telangana
      • Hyderabad, Telangana, India

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Very LBW (≤1.5kg)* or very preterm (≤32 weeks) infants admitted to NICU at study facility within 24 hours of birth for in-born infants and up to 48 hours for out-born**
  • Mother and infant alive during screening
  • Mother age 18+ years
  • Lives within catchment areas of the facility
  • Mother intends to stay in catchment area of the study facility for at least 3 months
  • At randomization: Infant receiving at least 60 mL/kg/day of human milk***

Exclusion Criteria:

  • Lives outside the defined catchment area
  • Congenital abnormalities or acquired conditions that interfere with feeding or placement of nasogastric/orogastric tube [cleft lip/palate, toxoplasmosis, other agents, rubella, cytomegalovirus, and herpes (TORCH), Trisomy 21, congenital cardiac defect, neural tube defect, gastrointestinal tract anomalies, hydrocephalus, NEC]
  • Severe birth asphyxia
  • Critically ill (i.e. not on enteral feeds)
  • Unknown date of birth and unknown gestational age

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Routine fortification of human milk with human milk fortifier using a standardized clinical protocol

Enrolled participants in the intervention arm will be exposed to:

  • Provision of guideline-driven standard of care specifically for VPT/ VLBW babies
  • Encouragement to express breast milk with breast pumps
  • Adherence to a clinical guideline including targets for initiation and advancement of breast milk feeding for VPT/ VLBW babies based on birthweight
  • Fortification of human milk with HMF
  • Adherence to standardized stopping criteria (i.e., stopping adherence to clinical feeding guideline AND stopping routine fortification of human milk)
Dietary supplement: Human Milk Fortifier

Human milk fortifier added to expressed human milk (mother's own milk or pasteurized donor human milk) per feed per manufacturer's instructions for a minimum of 21 days (in-facility provision only)

  • Clinical feeding guideline including targets for initiation and advancement of breast milk feeding
  • Provision of guideline-driven standard of care [facility-based lactation support/feeding counseling + KMC + WASH package (referred to as facility-based FSP+) and breast pumps]
Other Names:
  • Volume targets
  • Guideline-driven standard of care
Other: Volume targets
  • Clinical feeding guideline including targets for initiation and advancement of breast milk feeding
  • Provision of guideline-driven standard of care [facility-based lactation support/feeding counseling + KMC + WASH package (referred to as facility-based FSP+) and breast pumps]
Other Names:
  • Guideline driven standard of care
Active Comparator: No routine fortification of human milk using a standardized clinical protocol

Participants in the control group will have the same exposures as the participants in the intervention group EXCEPT for the human milk consumed will not be fortified with HMF.

  • Provision of guideline-driven standard of care specifically for VPT/ VLBW babies
  • Encouragement to express with breast pumps
  • Adherence to a clinical guideline including targets for initiation and advancement of breast milk feeding for VPT/ VLBW babies based on birthweight
  • Adherence to standardized stopping criteria (i.e., stopping adherence to clinical feeding guideline)
Other: Volume targets
  • Clinical feeding guideline including targets for initiation and advancement of breast milk feeding
  • Provision of guideline-driven standard of care [facility-based lactation support/feeding counseling + KMC + WASH package (referred to as facility-based FSP+) and breast pumps]
Other Names:
  • Guideline driven standard of care

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Length-for-age Z score (LAZ)
Time Frame: 3 Months
Mean LAZ (SD, range) measured at birth, 2 weeks, 4 weeks and 3 months of age
3 Months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Length of Stay
Time Frame: From date of randomization until the date of facility discharge or date of death from any cause, whichever came first, assessed up to 3 months of age.
Mean (SD) number of days admitted in the study facility from randomization to facility discharge
From date of randomization until the date of facility discharge or date of death from any cause, whichever came first, assessed up to 3 months of age.
Feeding intolerance
Time Frame: From randomization to facility discharge, assessed up to 3 months of age
% infants identified with feeding intolerance
From randomization to facility discharge, assessed up to 3 months of age
Weight growth velocity
Time Frame: From randomization to facility discharge, assessed up to 3 months of age
% infants attaining 15 g/kg/day
From randomization to facility discharge, assessed up to 3 months of age
Length gain
Time Frame: From randomization to facility discharge, assessed up to 3 months of age.
Mean (SD) change in length (mm/week)
From randomization to facility discharge, assessed up to 3 months of age.
Head circumference gain
Time Frame: From randomization to facility discharge, assessed up to 3 months of age
Mean (SD) change in head circumference (mm per week)
From randomization to facility discharge, assessed up to 3 months of age
Necrotizing enterocolitis (NEC)
Time Frame: From randomization to facility discharge, assessed up to 3 months of age.
% infants diagnosed with NEC
From randomization to facility discharge, assessed up to 3 months of age.
Sepsis/possible serious bacterial infection (PSBI)
Time Frame: From randomization to facility discharge, assessed up to 3 months of age
% diagnosed with sepsis or possible serious bacterial infection (PSBI)
From randomization to facility discharge, assessed up to 3 months of age
Infant mortality
Time Frame: From randomization to 3 months of age
% infants died
From randomization to 3 months of age
Birthweight regain
Time Frame: 2 weeks of age
% infants who regain birthweight by 2 weeks of age
2 weeks of age
Mean weight growth velocity (4 weeks)
Time Frame: From randomization to 4 weeks of age
Mean (SD) change in weight (growth) at 4 weeks of age
From randomization to 4 weeks of age
Neonatal mortality (4 weeks)
Time Frame: From randomization to 4 weeks of age
% of neonates who died up to 4 weeks of age
From randomization to 4 weeks of age
Sepsis/possible serious bacterial infection (PSBI, 4 weeks)
Time Frame: From randomization to 4 weeks of age
% of infants diagnosed with sepsis/PSBI up to 4 weeks of age
From randomization to 4 weeks of age
Mean weight growth velocity
Time Frame: From randomization to facility discharge, assessed up to 3 months of age.
Mean change in infant weight (growth) calculated in grams/kilogram/day (g/kg/day)
From randomization to facility discharge, assessed up to 3 months of age.
Weight-for-age Z score (WAZ)
Time Frame: 3 months of age
Mean (SD) WAZ at 3 months of age
3 months of age
Weight-for-length Z score (WLZ)
Time Frame: 3 months of age
Mean (SD) weight-for-length Z score (WLZ) at 3 months of age
3 months of age
Head circumference-for-age Z score (HcAZ)
Time Frame: 3 months of age
Mean (SD) HcAZ
3 months of age
Change in WAZ
Time Frame: From randomization to 3 months of age
Change in WAZ from randomization to 3 months of age
From randomization to 3 months of age
Change in LAZ
Time Frame: From randomization to 3 months of age
Change in LAZ from randomization to 3 months of age
From randomization to 3 months of age

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Harvard School of Public Health (HSPH)

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Boston Children's Hospital
Emory University
Brigham and Women's Hospital
PATH
University of North Carolina
Jawaharlal Nehru Medical College
Muhimbili University of Health and Allied Sciences

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Katherine Semrau, PhD, MPH, Ariadne Labs | Harvard TH Chan School of Public Health and Brigham and Womens Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 16, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 31, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 31, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 26, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 3, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 9, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 21, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 16, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IRB23-0304

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

De-identified datasets will be released after the close of the project in a data sharing repository, such as Harvard Dataverse or similar, in a format readable by analytics tools. Harvard Dataverse is an online data repository where you can share, preserve, cite, explore, and analyze research data. Datasets and data dictionaries will be provided in compliance with the ethical review board requirements. As part of the Harvard Dataverse system, registration to download datasets is required. External partners (those not involved in the study) must provide their contact information and describe their intention of data use.

IPD Sharing Time Frame

Study data will be available after study completion, expected in mid-2027.

IPD Sharing Access Criteria

Data will be available on Harvard Dataverse and users will register for access stating their intent to use the data.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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