Infant, Premature, DiseasesM-MILK RCTNCT07216664
Multisensory Early Oral Administration of Human Milk (M-MILK) for Very Preterm Infants
A study testing Multisensory early oral administration of human milk in people with Infant, Premature, Diseases, run by Loyola University at 2 sites in United States.
Trial summary
The goal of this clinical trial is to learn if the multisensory early oral administration of human milk (M-MILK) intervention helps infants who are born younger than 32 weeks gestational age (very preterm infants). Read more about this study
- Who is it for?
- Ages 23 to 32 weeks
- Conditions the study is for
- Infant, Premature, Diseases
- What is being tested?
- Multisensory early oral administration of human milk
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 125 participants
- Where
- 2 sitesUnited States
- Study dates
- 3 Nov 2025to 31 May 2031
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 23 to 32 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Born at ≤ 32 weeks gestational age.
- Receiving mother's own milk and/or donor human milk at the time of screening.
Who cannot join
- Receiving only formula.
- Gastrointestinal defects, i.e., cleft lip or cleft palate.
- Congenital cardiac defects requiring surgery.
- Necrotizing enterocolitis.
- Chromosomal abnormalities.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
Loyola University Chicago
Maywood, Illinois, 60153
Thao Griffith, 4642209825, tgriffith1@luc.edu
- Recruiting
Loyola University Medical Center
Maywood, Illinois, 60153
Thao Griffith, 4642209825, tgriffith1@luc.edu
About this study
Official title: Randomized Controlled Trial of Multisensory Early Oral Administration of Human Milk (M-MILK) for Very Preterm Infants: Enhancing Stress Regulation, Neurodevelopment, and Oral Feeding Skills
The goal of this clinical trial is to learn if the multisensory early oral administration of human milk (M-MILK) intervention helps infants who are born younger than 32 weeks gestational age (very preterm infants). The main question that this clinical trial aims to answer is: Does M-MILK improve stress regulation, support optimal neurodevelopment, and promote competent oral feeding skills in very preterm infants?
Researchers will compare M-MILK to the standard of care to see if M-MILK helps very preterm infants. Specifically, researchers will compare the differences in:
- Cortisol levels
- DNA methylation of the two stress related genes (NR3C1 and HSD11B2)
- Neurodevelopment
- Oral feeding skills Participants in the M-MILK group will receive standard of care plus M-MILK intervention, which starts on day 3 of life and continues until they begin their oral feeding. M-MILK will be provided by clinical research nurses, during the day shift, up to 4 times a day. Participants in the standard of care group will continue to receive their usual care.
- Conditions
- Infant, Premature, Diseases
- Being tested
- Multisensory early oral administration of human milk
- Medical subject headings
- Infant, Premature, Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Multisensory early oral administration of human milkOther
Also called M-MILK
M-MILK is implemented starting on day 3 of life, during the day shift, after every hands-on care, during the beginning of a full gavage feeding, and up to 4 times a day. Infants receive M-MILK in small droplets via a 1-ml syringe. M-MILK will cease upon oral feeding initiation. Infants will receive either mother's own milk or donor's milk based on availability. Infants may receive up to 1 mL of milk each time based on their cues and responses. The 1 mL volume intake is included as part of their oral caloric intake. M-MILK is provided by research nurses or parents.
| Study group | Role | What they receive |
|---|---|---|
| M-MILK Group | Experimental | Infants in the M-MILK group will receive M-MILK intervention and standard of care. M-MILK is implemented starting on day 3 of life, during the day shift, after every hands-on care, during the beginning of a full gavage feeding, and up to 4 times a day. Infants receive M-MILK in small droplets via a 1-ml syringe. M-MILK will cease upon oral feeding initiation. Infants will receive either mother's own milk or donor's milk based on availability. Infants may receive up to 1 mL of milk each time based on their cues and responses. The 1 mL volume intake is included as part of their oral caloric intake. M-MILK is provided by research nurses or parents. Receives: Other: Multisensory early oral administration of human milk |
| Control Group | No intervention | Infants in the Control group will receive standard of care. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Oral feeding Skills: EFS assessment total score at PO Initiation
We will evaluate oral feeding skills using the Early Feeding Skills Assessment (EFS) at oral feeding (PO) initiation. The EFS provides a summary score for each of the 5 subscale (respiratory regulation, oral-motor functioning, swallowing coordination, engagement, and physiologic stability), as well as a total summary score. Higher EFS summary scores indicate more competent oral feeding skills.
Measured: Up to 12 weeks after birth.
Oral Feeding Skills: EFS assessment total score at 36 Weeks PMA
We will evaluate oral feeding skills using the Early Feeding Skills Assessment (EFS) at 36 weeks post-menstrual age (PMA). The EFS provides a summary score for each of the 5 subscale (respiratory regulation, oral-motor functioning, swallowing coordination, engagement, and physiologic stability), as well as a total summary score. Higher EFS summary scores indicate more competent oral feeding skills.
Measured: 36 weeks postmenstrual age.
Secondary outcomes (19)
Stress Regulation: Salivary Cortisol at PO Initiation
We will evaluate stress regulation, measured by salivary cortisol levels (μg/dL) at oral feeding (PO) initiation.
Measured: Up to 12 weeks after birth.
Stress Regulation: Salivary Cortisol at 36 Weeks PMA
We will evaluate stress regulation, measured by salivary cortisol levels (μg/dL) at 36 weeks PMA.
Measured: At 36 weeks postmenstrual age.
Stress Regulation: Buccal Cell DNAm of NR3C1 Exon 1F Promoter at PO Initiation
We will evaluate stress regulation, measured by buccal cell DNA methylation (DNAm) of NR3C1 Exon 1F promoter at oral feeding (PO) initiation. We anticipate to cover 33 CpG sites within the NR3C1 Exon 1F promoter. Methylation percentage (%) will calculated per CpG site (aligning with the human reference genome hg38).
Measured: Up to 12 weeks after birth.
Stress Regulation: Buccal Cell DNAm of NR3C1 Exon 1F Promoter at 36 Weeks PMA
We will evaluate stress regulation, measured by buccal cell DNA methylation (DNAm) of NR3C1 Exon 1F promoter at 36 weeks post-menstrual age (PMA). We anticipate to cover 33 CpG sites within the NR3C1 Exon 1F promoter. Methylation percentage (%) will calculated per CpG site (aligning with the human reference genome hg38).
Measured: At 36 weeks postmenstrual age.
Stress Regulation: Buccal Cell DNAm of HSD11B2 Promoter at PO Initiation
We will evaluate stress regulation, measured by buccal cell DNA methylation (DNAm) of HSD11B2 promoter at oral feeding (PO) initiation. We anticipate to cover 30 CpG sites within the HSD11B2 promoter. Methylation percentage (%) will calculated per CpG site (aligning with the human reference genome hg38).
Measured: Up to 12 weeks after birth.
Stress Regulation: Buccal Cell DNAm of HSD11B2 Promoter at 36 Weeks PMA
We will evaluate stress regulation, measured by buccal cell DNA methylation (DNAm) of HSD11B2 promoter at 36 weeks post-menstrual age (PMA). We anticipate to cover 30 CpG sites within the HSD11B2 promoter. Methylation percentage (%) will calculated per CpG site (aligning with the human reference genome hg38).
Measured: At 36 weeks postmenstrual age.
Neurodevelopment: NNNS-II Attention score 36 Weeks PMA
We will evaluate neurodevelopment using the NeoNatal Neurobehavioral Scale (NNNS-II) at 36 weeks post-menstrual age (PMA). The NNNS-II provides a summary score for each of the 13 domain (attention, handling, self-regulation, habituation, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, quality of movement, and stress/abstinence). High-risk neurodevelopment is characterized by higher scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence, along with lower score in quality of movement, attention, self-regulation, habituation. Low-risk neurodevelopment is characterized by higher scores in attention, self-regulation, habituation, and quality of movement, along with lower scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence.
Measured: At 36 weeks postmenstrual age.
Neurodevelopment: NNNS-II Handling score 36 Weeks PMA
We will evaluate neurodevelopment using the NeoNatal Neurobehavioral Scale (NNNS-II) at 36 weeks post-menstrual age (PMA). The NNNS-II provides a summary score for each of the 13 domain (attention, handling, self-regulation, habituation, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, quality of movement, and stress/abstinence). High-risk neurodevelopment is characterized by higher scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence, along with lower score in quality of movement, attention, self-regulation, habituation. Low-risk neurodevelopment is characterized by higher scores in attention, self-regulation, habituation, and quality of movement, along with lower scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence.
Measured: At 36 weeks postmenstrual age.
Neurodevelopment: NNNS-II Self-Regulation 36 Weeks PMA
We will evaluate neurodevelopment using the NeoNatal Neurobehavioral Scale (NNNS-II) at 36 weeks post-menstrual age (PMA). The NNNS-II provides a summary score for each of the 13 domain (attention, handling, self-regulation, habituation, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, quality of movement, and stress/abstinence). High-risk neurodevelopment is characterized by higher scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence, along with lower score in quality of movement, attention, self-regulation, habituation. Low-risk neurodevelopment is characterized by higher scores in attention, self-regulation, habituation, and quality of movement, along with lower scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence.
Measured: At 36 weeks postmenstrual age.
Neurodevelopment: NNNS-II Habituation score 36 Weeks PMA
We will evaluate neurodevelopment using the NeoNatal Neurobehavioral Scale (NNNS-II) at 36 weeks post-menstrual age (PMA). The NNNS-II provides a summary score for each of the 13 domain (attention, handling, self-regulation, habituation, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, quality of movement, and stress/abstinence). High-risk neurodevelopment is characterized by higher scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence, along with lower score in quality of movement, attention, self-regulation, habituation. Low-risk neurodevelopment is characterized by higher scores in attention, self-regulation, habituation, and quality of movement, along with lower scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence.
Measured: At 36 weeks postmenstrual age.
Neurodevelopment: NNNS-II Arousal score 36 Weeks PMA
We will evaluate neurodevelopment using the NeoNatal Neurobehavioral Scale (NNNS-II) at 36 weeks post-menstrual age (PMA). The NNNS-II provides a summary score for each of the 13 domain (attention, handling, self-regulation, habituation, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, quality of movement, and stress/abstinence). High-risk neurodevelopment is characterized by higher scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence, along with lower score in quality of movement, attention, self-regulation, habituation. Low-risk neurodevelopment is characterized by higher scores in attention, self-regulation, habituation, and quality of movement, along with lower scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence.
Measured: At 36 weeks postmenstrual age.
Neurodevelopment: NNNS-II Excitability score 36 Weeks PMA
We will evaluate neurodevelopment using the NeoNatal Neurobehavioral Scale (NNNS-II) at 36 weeks post-menstrual age (PMA). The NNNS-II provides a summary score for each of the 13 domain (attention, handling, self-regulation, habituation, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, quality of movement, and stress/abstinence). High-risk neurodevelopment is characterized by higher scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence, along with lower score in quality of movement, attention, self-regulation, habituation. Low-risk neurodevelopment is characterized by higher scores in attention, self-regulation, habituation, and quality of movement, along with lower scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence.
Measured: At 36 weeks postmenstrual age.
Neurodevelopment: NNNS-II Lethargy score 36 Weeks PMA
We will evaluate neurodevelopment using the NeoNatal Neurobehavioral Scale (NNNS-II) at 36 weeks post-menstrual age (PMA). The NNNS-II provides a summary score for each of the 13 domain (attention, handling, self-regulation, habituation, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, quality of movement, and stress/abstinence). High-risk neurodevelopment is characterized by higher scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence, along with lower score in quality of movement, attention, self-regulation, habituation. Low-risk neurodevelopment is characterized by higher scores in attention, self-regulation, habituation, and quality of movement, along with lower scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence.
Measured: At 36 weeks postmenstrual age.
Neurodevelopment: NNNS-II Hypertonicity score 36 Weeks PMA
We will evaluate neurodevelopment using the NeoNatal Neurobehavioral Scale (NNNS-II) at 36 weeks post-menstrual age (PMA). The NNNS-II provides a summary score for each of the 13 domain (attention, handling, self-regulation, habituation, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, quality of movement, and stress/abstinence). High-risk neurodevelopment is characterized by higher scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence, along with lower score in quality of movement, attention, self-regulation, habituation. Low-risk neurodevelopment is characterized by higher scores in attention, self-regulation, habituation, and quality of movement, along with lower scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence.
Measured: At 36 weeks postmenstrual age.
Neurodevelopment: NNNS-II Hypotonicity score 36 Weeks PMA
We will evaluate neurodevelopment using the NeoNatal Neurobehavioral Scale (NNNS-II) at 36 weeks post-menstrual age (PMA). The NNNS-II provides a summary score for each of the 13 domain (attention, handling, self-regulation, habituation, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, quality of movement, and stress/abstinence). High-risk neurodevelopment is characterized by higher scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence, along with lower score in quality of movement, attention, self-regulation, habituation. Low-risk neurodevelopment is characterized by higher scores in attention, self-regulation, habituation, and quality of movement, along with lower scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence.
Measured: At 36 weeks postmenstrual age.
Neurodevelopment: NNNS-II Nonoptimal Reflexes score 36 Weeks PMA
We will evaluate neurodevelopment using the NeoNatal Neurobehavioral Scale (NNNS-II) at 36 weeks post-menstrual age (PMA). The NNNS-II provides a summary score for each of the 13 domain (attention, handling, self-regulation, habituation, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, quality of movement, and stress/abstinence). High-risk neurodevelopment is characterized by higher scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence, along with lower score in quality of movement, attention, self-regulation, habituation. Low-risk neurodevelopment is characterized by higher scores in attention, self-regulation, habituation, and quality of movement, along with lower scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence.
Measured: At 36 weeks postmenstrual age.
Neurodevelopment: NNNS-II Asymmetric Reflexes score 36 Weeks PMA
We will evaluate neurodevelopment using the NeoNatal Neurobehavioral Scale (NNNS-II) at 36 weeks post-menstrual age (PMA). The NNNS-II provides a summary score for each of the 13 domain (attention, handling, self-regulation, habituation, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, quality of movement, and stress/abstinence). High-risk neurodevelopment is characterized by higher scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence, along with lower score in quality of movement, attention, self-regulation, habituation. Low-risk neurodevelopment is characterized by higher scores in attention, self-regulation, habituation, and quality of movement, along with lower scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence.
Measured: At 36 weeks postmenstrual age.
Neurodevelopment: NNNS-II Quality of Movement score 36 Weeks PMA
We will evaluate neurodevelopment using the NeoNatal Neurobehavioral Scale (NNNS-II) at 36 weeks post-menstrual age (PMA). The NNNS-II provides a summary score for each of the 13 domain (attention, handling, self-regulation, habituation, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, quality of movement, and stress/abstinence). High-risk neurodevelopment is characterized by higher scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence, along with lower score in quality of movement, attention, self-regulation, habituation. Low-risk neurodevelopment is characterized by higher scores in attention, self-regulation, habituation, and quality of movement, along with lower scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence.
Measured: At 36 weeks postmenstrual age.
Neurodevelopment: NNNS-II Stress/Abstinence score 36 Weeks PMA
We will evaluate neurodevelopment using the NeoNatal Neurobehavioral Scale (NNNS-II) at 36 weeks post-menstrual age (PMA). The NNNS-II provides a summary score for each of the 13 domain (attention, handling, self-regulation, habituation, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, quality of movement, and stress/abstinence). High-risk neurodevelopment is characterized by higher scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence, along with lower score in quality of movement, attention, self-regulation, habituation. Low-risk neurodevelopment is characterized by higher scores in attention, self-regulation, habituation, and quality of movement, along with lower scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence.
Measured: At 36 weeks postmenstrual age.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2025
- Study start3 Nov 2025
- Primary completion31 May 2030 (estimated)
- Study completion31 May 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Infant, Premature, DiseasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 125 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Loyola University
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Rush University Medical Center
- Responsible party
- Sponsor
- Investigators
- Thao Griffith, PhD, Principal investigator, Loyola University Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07216664
- Sponsor's protocol ID
- 218601
- Acronym
- M-MILK RCT
- Status last verified
- Jan 2026
- First submitted
- 26 Sep 2024
- Last updated
- 20 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: We do not plan to share IPD to ensure confidentiality and privacy participants. We have plans to share only de-identifiable data. Data will be shared in accordance with the NIH Data Sharing Policy. Data will be shared on reasonable request to Loyola University Chicago through a Data Use Agreement (DUA).
Publications
Griffith T, Janusek L, White-Traut R, Green SJ, Sachin A, Joyce C. Study Protocol for a Randomized Controlled Trial of Multisensory Early Oral Administration of Human Milk (M-MILK) for Very Preterm Infants: Enhancing Stress Regulation, Neurodevelopment, and Oral Feeding Skills. Biol Res Nurs. 2026 Jul;28(3):464-478. doi: 10.1177/10998004261418708. Epub 2026 Jan 19.
PubMed 41554032
Study at a glance
From the registry record, last updated by the sponsor on 20 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Controlled Trial of Multisensory Early Oral Administration of Human Milk (M-MILK) for Very Preterm Infants: Enhancing Stress Regulation, Neurodevelopment, and Oral Feeding Skills
- ClinicalTrials.gov ID
- NCT07216664
- Acronym / sponsor ID
- M-MILK RCT / 218601
- Conditions
- Infant, Premature, Diseases
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 125 participants (estimated)
- Lead sponsor
- Loyola UniversityUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Rush University Medical Center
- Study start
- 3 Nov 2025 (actual)
- Primary completion
- 31 May 2030 (estimated)
- Study completion
- 31 May 2031 (estimated)
- First posted
- 14 Oct 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical trial is to learn if the multisensory early oral administration of human milk (M-MILK) intervention helps infants who are born younger than 32 weeks gestational age (very preterm infants). The main question that this clinical trial aims to answer is: Does M-MILK improve stress regulation, support optimal neurodevelopment, and promote competent oral feeding skills in very preterm infants?
Researchers will compare M-MILK to the standard of care to see if M-MILK helps very preterm infants. Specifically, researchers will compare the differences in:
- Cortisol levels
- DNA methylation of the two stress related genes (NR3C1 and HSD11B2)
- Neurodevelopment
- Oral feeding skills Participants in the M-MILK group will receive standard of care plus M-MILK intervention, which starts on day 3 of life and continues until they begin their oral feeding. M-MILK will be provided by clinical research nurses, during the day shift, up to 4 times a day. Participants in the standard of care group will continue to receive their usual care.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| M-MILK Group | Experimental | Other: Multisensory early oral administration of human milkInfants in the M-MILK group will receive M-MILK intervention and standard of care. M-MILK is implemented starting on day 3 of life, during the day shift, after every hands-on care, during the beginning of a full gavage feeding, and up to 4 times a day. Infants receive M-MILK in small droplets via a 1-ml syringe. M-MILK will cease upon oral feeding initiation. Infants will receive either mother's own milk or donor's milk based on availability. Infants may receive up to 1 mL of milk each time based on their cues and responses. The 1 mL volume intake is included as part of their oral caloric intake. M-MILK is provided by research nurses or parents. |
| Control Group | No intervention | –Infants in the Control group will receive standard of care. |
Who may qualify
- Ages
- 23 to 32 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- Born at ≤ 32 weeks gestational age.
- Receiving mother's own milk and/or donor human milk at the time of screening.
Key exclusion criteria (5 listed)
- Receiving only formula.
- Gastrointestinal defects, i.e., cleft lip or cleft palate.
- Congenital cardiac defects requiring surgery.
- Necrotizing enterocolitis.
- Chromosomal abnormalities.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Multisensory early oral administration of human milkAlso: M-MILKM-MILK is implemented starting on day 3 of life, during the day shift, after every hands-on care, during the beginning of a full gavage feeding, and up to 4 times a day. Infants receive M-MILK in small droplets via a 1-ml syringe. M-MILK will cease upon oral feeding initiation. Infants will receive either mother's own milk or donor's milk based on availability. Infants may receive up to 1 mL of milk each time based on their cues and responses. The 1 mL volume intake is included as part of their oral caloric intake. M-MILK is provided by research nurses or parents. | Other | M-MILK Group |
Primary outcome
Oral feeding Skills: EFS assessment total score at PO Initiation
Time frame: Up to 12 weeks after birth.
We will evaluate oral feeding skills using the Early Feeding Skills Assessment (EFS) at oral feeding (PO) initiation. The EFS provides a summary score for each of the 5 subscale (respiratory regulation, oral-motor functioning, swallowing coordination, engagement, and physiologic stability), as well as a total summary score. Higher EFS summary scores indicate more competent oral feeding skills.
Oral Feeding Skills: EFS assessment total score at 36 Weeks PMA
Time frame: 36 weeks postmenstrual age.
We will evaluate oral feeding skills using the Early Feeding Skills Assessment (EFS) at 36 weeks post-menstrual age (PMA). The EFS provides a summary score for each of the 5 subscale (respiratory regulation, oral-motor functioning, swallowing coordination, engagement, and physiologic stability), as well as a total summary score. Higher EFS summary scores indicate more competent oral feeding skills.
19 secondary outcomes
Stress Regulation: Salivary Cortisol at PO Initiation
Time frame: Up to 12 weeks after birth.
Stress Regulation: Salivary Cortisol at 36 Weeks PMA
Time frame: At 36 weeks postmenstrual age.
Stress Regulation: Buccal Cell DNAm of NR3C1 Exon 1F Promoter at PO Initiation
Time frame: Up to 12 weeks after birth.
Stress Regulation: Buccal Cell DNAm of NR3C1 Exon 1F Promoter at 36 Weeks PMA
Time frame: At 36 weeks postmenstrual age.
Stress Regulation: Buccal Cell DNAm of HSD11B2 Promoter at PO Initiation
Time frame: Up to 12 weeks after birth.
Stress Regulation: Buccal Cell DNAm of HSD11B2 Promoter at 36 Weeks PMA
Time frame: At 36 weeks postmenstrual age.
Neurodevelopment: NNNS-II Attention score 36 Weeks PMA
Time frame: At 36 weeks postmenstrual age.
Neurodevelopment: NNNS-II Handling score 36 Weeks PMA
Time frame: At 36 weeks postmenstrual age.
Neurodevelopment: NNNS-II Self-Regulation 36 Weeks PMA
Time frame: At 36 weeks postmenstrual age.
Neurodevelopment: NNNS-II Habituation score 36 Weeks PMA
Time frame: At 36 weeks postmenstrual age.
Neurodevelopment: NNNS-II Arousal score 36 Weeks PMA
Time frame: At 36 weeks postmenstrual age.
Neurodevelopment: NNNS-II Excitability score 36 Weeks PMA
Time frame: At 36 weeks postmenstrual age.
Neurodevelopment: NNNS-II Lethargy score 36 Weeks PMA
Time frame: At 36 weeks postmenstrual age.
Neurodevelopment: NNNS-II Hypertonicity score 36 Weeks PMA
Time frame: At 36 weeks postmenstrual age.
Neurodevelopment: NNNS-II Hypotonicity score 36 Weeks PMA
Time frame: At 36 weeks postmenstrual age.
Neurodevelopment: NNNS-II Nonoptimal Reflexes score 36 Weeks PMA
Time frame: At 36 weeks postmenstrual age.
Neurodevelopment: NNNS-II Asymmetric Reflexes score 36 Weeks PMA
Time frame: At 36 weeks postmenstrual age.
Neurodevelopment: NNNS-II Quality of Movement score 36 Weeks PMA
Time frame: At 36 weeks postmenstrual age.
Neurodevelopment: NNNS-II Stress/Abstinence score 36 Weeks PMA
Time frame: At 36 weeks postmenstrual age.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jan 2026.
- Derived from this study: PubMed 41554032Griffith T, Janusek L, White-Traut R, Green SJ, Sachin A, Joyce C. Study Protocol for a Randomized Controlled Trial of Multisensory Early Oral Administration of Human Milk (M-MILK) for Very Preterm Infants: Enhancing Stress Regulation, Neurodevelopment, and Oral Feeding Skills. Biol Res Nurs. 2026 Jul;28(3):464-478. doi: 10.1177/10998004261418708. Epub 2026 Jan 19.
- Individual participant dataSharing planned: No. We do not plan to share IPD to ensure confidentiality and privacy participants. We have plans to share only de-identifiable data. Data will be shared in accordance with the NIH Data Sharing Policy. Data will be shared on reasonable request to Loyola University Chicago through a Data Use Agreement (DUA).
Related trials for Infant, Premature, Diseases
Not yet recruiting
nCPAP-NAVA-Backup Versus Standard nCPAP for Severe Apnea in Preterm Infants ≤28 Weeks
Apnea of Prematurity
Recruiting
Study of the Influence of Intraperitoneal Insufflation of CO2 by Laparoscopy on the Short-term Evolution of Premature Infants With Ulcerative Necrotizing Enterocolitis
Preterm Birth, Enterocolitis, Necrotizing
Recruiting
Comparing Surfactant Administration Through Supraglottic Airway and Thin Catheter for Preterm Infants
Surfactant, Respiratory Distress Syndrome (Neonatal)
Recruiting
Optimization of Saturation Targets And Resuscitation Trial (OptiSTART)
Premature Infants, Bronchopulmonary Dysplasia
RecruitingObservational study
Growing Little PEAPODS Study
Premature Birth, Premature Infant
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Thao Griffith, PhD principal investigator
Loyola University Chicago
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Multisensory early oral administration of human milk in people with Infant, Premature, Diseases, run by Loyola University at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 20 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Thao Griffith, PhD (464-220-9825, tgriffith1@luc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Oral feeding Skills: EFS assessment total score at PO Initiation (time frame: Up to 12 weeks after birth.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07216664, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jan 2026.