LIFT-UP: Randomized Controlled Trial of Fortification of Human Milk

NCT06765863 | Recruiting DMC

• 1 other identifier: IRB23-0304
• Study Type: interventional
• Target: 776
• Locations: 1 country
• Sites: 4

Brief Summary

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?

Conditions

Very Preterm Infant; Very Low Birthweight

Keywords

very preterm; very low birthweight; fortification; human milk

Outcome Measures

Primary Outcomes (1)

• Length-for-age Z score (LAZ)

  Mean LAZ (SD, range) measured at birth, 2 weeks, 4 weeks and 3 months of age

  3 Months

Secondary Outcomes (18)

• Length of Stay

  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

  From randomization to facility discharge, assessed up to 3 months of age

• Weight growth velocity

  From randomization to facility discharge, assessed up to 3 months of age

• Length gain

  From randomization to facility discharge, assessed up to 3 months of age.

• Head circumference gain

  From randomization to facility discharge, assessed up to 3 months of age

Study Arms (2)

Routine fortification of human milk with human milk fortifier using a standardized clinical protocol

EXPERIMENTAL

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; Other: Volume targets

No routine fortification of human milk using a standardized clinical protocol

ACTIVE COMPARATOR

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

Interventions

Volume targets OTHER

* Clinical feeding guideline including targets for initiation and advancement of breast milk feeding * Provision of guideline-driven standard of care \[facility-based lactation support/feeding counseling + KMC + WASH package (referred to as facility-based FSP+) and breast pumps\]

Also known as: Guideline driven standard of care

No routine fortification of human milk using a standardized clinical protocol; Routine fortification of human milk with human milk fortifier using a standardized clinical protocol

Human Milk Fortifier DIETARY_SUPPLEMENT

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 \[facility-based lactation support/feeding counseling + KMC + WASH package (referred to as facility-based FSP+) and breast pumps\]

Also known as: Volume targets, Guideline-driven standard of care

Routine fortification of human milk with human milk fortifier using a standardized clinical protocol

Eligibility Criteria

• Age: Up to 48 Hours
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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\*\*\*

You may not qualify if:

• 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

Sponsors & Collaborators

• Brigham and Women's Hospital: collaborator
• Muhimbili University of Health and Allied Sciences: collaborator
• Jawaharlal Nehru Medical College: collaborator
• PATH: collaborator
• University of North Carolina: collaborator
• Harvard School of Public Health (HSPH): lead
• Boston Children's Hospital: collaborator
• Emory University: collaborator

Study Sites (4)

Ballari Medical College and Research Centre

Ballary, Karnataka, India

RECRUITING

KLES Dr Prabhakar Kore Hospital & Medical Research Center

Belagavi, Karnataka, India

NOT YET RECRUITING

JJM Medical College

Davangere, Karnataka, India

RECRUITING

Niloufer Hospital

Hyderabad, Telangana, India

RECRUITING

Study Officials

• Katherine Semrau, PhD, MPH

  Ariadne Labs | Harvard TH Chan School of Public Health and Brigham and Womens Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ilana Dzuba, MHS

CONTACT

617-384-6555; idzuba@ariadnelabs.org

Linda Vesel, PhD, MPH

CONTACT

lvesel@ariadnelabs.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants (i.e. mother-infant dyads) will not be blinded and will know if the fortification is being provided to the infant as it will be mixed with human milk \[MOM or PHDM\] in the intervention arm. Clinical research staff will not be blinded as they are preparing and providing the intervention and control feeding assignments. Data collectors and the analysis team will be blinded to study arm assignments to reduce bias in data collection and analysis. These individuals (data collectors and analysis team) will be independent from the clinical study staff who are providing the intervention or control. For data analysis, groups will be labeled with a letter (A vs B) to conceal allocation assignment.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Deputy Director, Ariadne Labs & Director, BetterBirth Program; Associate Professor, HSPH

Model Details: Mother-infant dyads will be individually randomized 1:1 to the intervention or comparison arm.

Study Record Dates

• First Submitted: December 26, 2024
• First Posted: January 9, 2025
• Study Start: January 16, 2025
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): March 31, 2027
• Last Updated: January 21, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Study data will be available after study completion, expected in mid-2027.
• Access Criteria: Data will be available on Harvard Dataverse and users will register for access stating their intent to use the data.

Locations

IN (4)