Leveraging Optimal Tolerance in Undernourished Infants to Support Growth (LOTUS)

The goal of this study is to learn if InfaCore (IC) an energy and nutrient dense formulation (ENDF) can improve growth and tolerance in infants with or at risk of growth faltering when fed IC.

Study Overview

• Status: Not yet recruiting
• Conditions: Failure to Thrive; Faltering Growth
• Intervention / Treatment: Other: Infant Formula

Detailed Description

Rationale: The definition of FG/FTT was established by a group of experts in a report published in 2023 (Cooke et al., 2023). In this report they agreed a fall in weight-for-age z-score (WAZ) of ≥1.0 SD over a period of 1 or more months (excluding the first 2 weeks after birth) which includes at least 2-3 growth measurements (Cooke et al., 2023). It is also important to consider infants at risk who have static weight for extended periods e.g., >/=4 weeks. FG/FTT affects different populations and is estimated to be 10% of infants globally.

InfaCore (IC) an energy and nutrient dense formulation is indicated for infants and young children with FG/FTT defined above or for those at risk of developing e.g., with static weight for extended periods. At risk infants might include some or all of the following those with congenital heart disease (CHD) admitted for surgical procedures, those with critical illness (CI) or on the PICU, infants cystic fibrosis (CF) or other respiratory conditions including chronic lung disease (CLD), some forms of severe cerebral palsy (CP), and those requiring a surgical procedure or post-surgery.

Objective: To demonstrate growth and tolerance in infants with or at risk of growth faltering when fed IC an Energy and Nutrient Dense Formula (ENDF).

Study design: A prospective, single-centre, single-arm open label pilot study to show growth and tolerance in infants with/at risk of FG/FTT when fed an ENDF for 8 weeks.

• Study Type: Interventional
• Enrollment (Estimated): 35
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Chonnikant Visuthranukul, MD, PhD; Phone Number: 4903 +66 2256 4000; Email: deknet@gmail.com
• Study Contact Backup: Name: Eakkarin Mekangkul, MD

Study Locations

• Thailand
  • Bangkok
    • Bangkok, Bangkok, Thailand, 10330
      • Department of Pediatrics, Faculty of Medicine, Chulalongkorn University
      • Contact: Chonnikant Visuthranukul, MD, PhD; Phone Number: 4903 +66 2256 4000; Email: deknet@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Infants aged from 1 month to </=12 months of age
• Infants taking at least 50% of daily intake from infant formula
• Diagnosis of FG (a fall in WAZ of ≥1.0 SD over 1 month or more - not including the first 2 weeks after birth) or risk of FG (static weight for >/= 1 month)
• Infants >/=37 weeks gestation at time of recruitment
• Parent/ legal guardian willing to provide written informed consent

Exclusion Criteria:

• Exclusively Breastfed infants
• Infants with other medical problems that might independently affect intake (oral or otherwise) or who have specific nutrient needs not met by IC e.g. some gastrointestinal malformations, some renal and liver conditions, inborn errors of metabolism, galactosemia
• Infants on total parenteral nutrition
• Infants with cow milk protein allergy
• Infants with soy allergy
• Infants who participated in other studies within 2 weeks prior to recruitment
• Situations where the investigator has concerns about the willingness or ability of the parents/caregivers to comply with protocol requirements
• Infants who are on a vegan diet
• Infants who are allergic to fish
• Infants born preterm <37 weeks gestation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Interventional	Other: Infant Formula; Prospective, single-center, single-arm open label pilot study to show growth and tolerance in infants with/at risk of FG/FTT when fed an ENDF for 8 weeks.; Other Names: Energy and Nutrient Dense Infant Formula (ENDF)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body Weight	Body Weight	8 weeks
Change in body weight	The primary outcome is the change in weight-for-age Z-score from baseline to study completion, regardless of whether the value increases or decreases.	8 weeks

Collaborators and Investigators

• Sponsor: Dutch Medical Food

Publications and helpful links

General Publications

• Zhang H, Gu Y, Mi Y, Jin Y, Fu W, Latour JM. High-energy nutrition in paediatric cardiac critical care patients: a randomized controlled trial. Nurs Crit Care. 2019 Mar;24(2):97-102.
• World Health Organization (WHO). Child Growth Standards. [Online]. Available from: https://www.who.int/tools/child-growth-standards/standards/weight-for-age (Accessed August 2025).
• World Health Organization (WHO). Technical Report Series. Protein and amino acid requirements in human nutrition. Report of a Joint WHO/FAO/UNU Expert Consultation. World Health Organ Tech Rep Ser 2007;(935):1-265.
• Valla FV, Berthiller J, Gaillard-Le-Roux B et al. Faltering growth in the critically ill child: prevalence, risk factors, and impaired outcome. Eur J Pediatr. 2018 Mar;177(3):345-353.
• Shoham J & Duffield A. Proceedings of the World Health Organization / UNICEF /World Food Programme/United Nations High Commissioner for Refugees Consultation on the Management of Moderate Malnutrition in Children under 5 Years of Age. Food and Nutrition Bulletin. 2009;30(3_suppl3):S464-S474.
• Pineda D, Bingham R, Gates A, Thompson AB, Stansfield BK. Osmolality of fortified donor human milk: An experimental study. JPEN J Parenter Enteral Nutr. 2024 Jan;48(1):57-63.
• Novak EM, Innis SM. Impact of maternal dietary n-3 and n-6 fatty acids on milk medium-chain fatty acids and the implications for neonatal liver metabolism. Am J Physiol Endocrinol Metab. 2011 Nov;301(5):E807-17.
• Jackson AA. Protein requirements for catch-up growth. Proc Nutr Soc 1990; 49: 507-16.
• Hulst JM, Zwart H, Hop WC, Joosten KF. Dutch national survey to test the STRONGkids nutritional risk screening tool in hospitalized children. Clin Nutr. 2010 Feb;29(1):106-11.
• Food And Nutrition (FAO). Technical report series 1. 2001. [Online]. Available from: https://openknowledge.fao.org/server/api/core/bitstreams/65875dc7-f8c5-4a70-b0e1-f429793860ae/content (Accessed August 2025)
• Eveleens RD, Dungen DK, Verbruggen SCAT, Hulst JM, Joosten KFM. Weight improvement with the use of protein and energy enriched nutritional formula in infants with a prolonged PICU stay. J Hum Nutr Diet. 2019 Feb;32(1):3-10.
• Evans S, Twaissi H, Daly A, Davies P, Macdonald A. Should high-energy infant formula be given at full strength from its first day of usage? J Hum Nutr Diet. 2006 Jun;19(3):191-7; quiz 199-201.
• Ellis ZM, Tan HSG, Embleton ND, Sangild PT, van Elburg RM. Milk feed osmolality and adverse events in newborn infants and animals: a systematic review. Arch Dis Child Fetal Neonatal Ed. 2019 May;104(3):F333-F340.
• EUROPEAN DIRECTIVE - COMMISSION DELEGATED REGULATION (EU) (2016) - of 25 September 2015. Supplementing Regulation (EU) No 609/2013 of the European Parliament and of the Council as regards the specific compositional and information requirements for food for special medical purposes. 128. [Online]. Available from: file:///C:/Users/garve/Downloads/CELEX_32016R0128_EN_TXT.pdf
• EUROPEAN DIRECTIVE - COMMISSION DELEGATED REGULATION (EU) (2016). Compositional and information requirements for infant formula and follow-on formula. 127. [Online]. Available from: https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32016R0127&qid=1650372664210&from=EN. (Accessed 2025)
• Cooke R, Goulet O, Huysentruyt K, et al. Catch-Up Growth in Infants and Young Children With Faltering Growth: Expert Opinion to Guide General Clinicians. J Pediatr Gastroenterol Nutr. 2023 Jul 1;77(1):7-15.
• Clarke SE, Evans S, Macdonald A, Davies P, Booth IW. Randomized comparison of a nutrient-dense formula with an energy-supplemented formula for infants with faltering growth. J Hum Nutr Diet. 2007 Aug;20(4):329-39.
• Braegger C, Decsi T, Dias JA, Hartman C, Kolacek S, Koletzko B, Koletzko S, Mihatsch W, Moreno L, Puntis J, Shamir R, Szajewska H, Turck D, van Goudoever J; ESPGHAN Committee on Nutrition:. Practical approach to paediatric enteral nutrition: a comment by the ESPGHAN committee on nutrition. J Pediatr Gastroenterol Nutr. 2010 Jul;51(1):110-22.
• Ballard O, Morrow AL. Human milk composition: nutrients and bioactive factors. Pediatr Clin North Am. 2013;60(1):49-74.
• Alsharkawy A, Foud E, Mujahed A et al. Nutritional assessment and rehabilitation in children with bronchiectasis and childhood interstitial lung diseases: effects on pulmonary functions and clinical severity. Egypt Pediatric Association Gaz 2021;69, 42

Study record dates

Study Major Dates

• Study Start (Estimated): May 15, 2026
• Primary Completion (Estimated): May 15, 2026
• Study Completion (Estimated): May 15, 2027

Study Registration Dates

• First Submitted: April 18, 2026
• First Submitted That Met QC Criteria: April 18, 2026
• First Posted (Actual): April 24, 2026

Study Record Updates

• Last Update Posted (Actual): April 24, 2026
• Last Update Submitted That Met QC Criteria: April 18, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Failure to Thrive; LOTUS; Faltering Growth; Energy and Nutrient Dense Formula; Infacore
• Additional Relevant MeSH Terms: Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Failure to Thrive; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Beverages; Foods, Specialized; Milk Substitutes; Food, Formulated; Infant Food; Infant Formula
• Other Study ID Numbers: LOTUSV10

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No