Lactase-Assisted Control Trial On Weight GAin in INfants.

NCT07150884 | Recruiting

• 1 other identifier: 701/22-01-2025
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 2

Brief Summary

Lactose, a disaccharide that includes the monosaccharides glucose and galactose, is the main carbohydrate found exclusively in mammalian milk. Lactase is found in the intestinal mucosa and is located at the ends of the villi, while it is a factor of maximum clinical importance in milk tolerance and in the occurrence of diarrheal disease. Developmental lactase deficiency is defined as the relative lactase deficiency observed in premature newborns less than 34 weeks of gestation. In the immature gastrointestinal tract, lactase and other disaccharidas are deficient until at least 34 weeks of gestation. One study in premature babies reported a benefit from the use of lactase-supplemented or lactose-reduced formulas, while the use of lactose-containing formulas and human milk did not appear to have short- or long-term harmful effects on infants and infants. Up to 20% of dietary lactose can reach the colon in newborns and young infants. Due to the inadequate functional development of lactase, premature infants may not digest and absorb the main source of carbohydrate energy, lactose. The high osmotic load associated with indigestible lactose is one of the many possible causes of diarrhea and food intolerance in premature babies. As a result of diarrhea stools and small bowel damage, the already low functional activity of lactase will be further reduced affecting weight gain, while it takes up to 2 weeks for lactase activity to be restored. Carlson et al showed that the addition of lactase to premature formula reduces the amount of lactose by 70%, with a negligible effect on osmolarity. Previous studies have found that premature infants fed a reduced lactose formula had a better weight gain rate than those who took 100% lactose formula. In two of these studies, weight gain improved despite eating fewer calories. In the present study we intend to test whether the use of lactase to hydrolysis lactose in premature milk would result in better weight gain and improved dietary tolerance by taking the same calorie intake. This is a prospective, double-blind, randomized study to evaluate tolerance and weight gain in premature infants who received either (1) human milk or premature formula enriched with Delictase ® drops (lactase group) or (2) unfortified human milk or premature formula (control group). The study will be carried out at the Second Neonatal Clinic and Neonatal Intensive Care Unit of the Aristotle University of Thessaloniki, in premature newborns (gestational age \[GA\] 28-34 weeks) who will be hospitalized in the Neonatal Intensive Care Unit. The study will enroll newborns (1) with a gestational duration of 28 to 34 weeks, (2) who receive ≥75% of their energy needs intestinally, (3) with the absence of severe congenital malformations or gastrointestinal diseases, including necrotizing enterocolitis (NEC) (4) without taking postnatal steroids or diuretics. Small, suitable and large for newborns of gestational age will be eligible for the study. Exclusion criteria will be neonates whose guardians refuse to participate in the study, neonates with congenital malformations or gastrointestinal diseases, and neonates receiving postnatal steroids or diuretics. The participation of newborns in the study will take place after written consent of the parents after information.

Conditions

Premature - Weight 1000g-2499g or Gestation of 28-37weeks; Healthy

Keywords

Lactase; Prematurity; Human milk; Weight gain; Feeding intolerance

Outcome Measures

Primary Outcomes (1)

• Weigh Gain

  The main outcome variable will be weight gain (g/day).

  2-4 weeks

Secondary Outcomes (2)

• Body length

  2-4 weeks

• Head circumference

  2-4 weeks

Other Outcomes (2)

• Biochemistry

  2-4 weeks

• Feeding intolerance

  2-4 weeks

Study Arms (2)

Lactase-Fortified Milk

EXPERIMENTAL

Newborns in the lactase group will receive milk fortified with 2 drops of lactase/kg of body weight per meal. The enrichment of the milk with lactase drops will be carried out by the nurse on duty without it being known by the principal investigator to which group (lactase group or control group) each newborn belongs. Only a secondary researcher and the shift nurse will have access to neonatal randomization information. The lactase drops that will be used in the study will be Delictase®, which is a dietary supplement that helps the proper digestion of lactose through its breakdown. Delictase® lactase drops offer an exogenous source of the lactase enzyme, which is essential for the proper absorption and digestion of lactose, can be administered from birth, mixed into the administered milk and contain high levels of lactase (\>3,000 ALU\*). The supply of Delictase® lactase preparations will be carried out by Galenic Pharmacy, every 2 months at the study site.

Dietary Supplement: Lactase

Control

NO INTERVENTION

The feeding of the newborns of the study will be in accordance with the usual practices of the clinic, i.e. the first choice will be breast milk, the second the human milk of the donor from the milk bank and the third choice the formula of premature newborns. Breast milk boosters will be added to breast milk according to the usual clinic practices, i.e. when the volume of milk administered exceeds 25 ml per meal. Human milk is given an estimated caloric value of 68 kcal/100 mL, while premature formula is given 81 kcal/100 mL.

Interventions

Lactase DIETARY_SUPPLEMENT

The lactase drops that will be used in the study will be Delictase®, which is a dietary supplement that helps the proper digestion of lactose through its breakdown. Delictase® lactase drops offer an exogenous source of the lactase enzyme, which is essential for the proper absorption and digestion of lactose, can be administered from birth, mixed into the administered milk and contain high levels of lactase (\>3,000 ALU\*). The supply of Delictase® lactase preparations will be carried out by Galenic Pharmacy, every 2 months at the study site.

Lactase-Fortified Milk

Eligibility Criteria

• Age: 1 Day - 4 Weeks
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• The study will enrol newborns (1) with a gestational duration of 28 to 34 weeks, (2) who receive ≥75% of their energy needs intestinally, (3) with the absence of severe congenital malformations or gastrointestinal diseases, including necrotizing enterocolitis (NEC) (4) without taking postnatal steroids or diuretics. Small, suitable and large for newborns of gestational age will be eligible for the study.

Sponsors & Collaborators

• Aristotle University Of Thessaloniki: lead

Study Sites (2)

Papageorgiou General Hospital

Thessaloniki, Greece

ACTIVE NOT RECRUITING

Papageorgiou General Hospital

Thessaloniki, Greece

RECRUITING

Related Publications (16)

• Shulman RJ, Feste A, Ou C. Absorption of lactose, glucose polymers, or combination in premature infants. J Pediatr. 1995 Oct;127(4):626-31. doi: 10.1016/s0022-3476(95)70128-1.

  PMID: 7562290 BACKGROUND

• Kien CL, McClead RE, Cordero L Jr. Effects of lactose intake on lactose digestion and colonic fermentation in preterm infants. J Pediatr. 1998 Sep;133(3):401-5. doi: 10.1016/s0022-3476(98)70278-1.

  PMID: 9738725 BACKGROUND

• Kien CL, Liechty EA, Mullett MD. Effects of lactose intake on nutritional status in premature infants. J Pediatr. 1990 Mar;116(3):446-9. doi: 10.1016/s0022-3476(05)82842-2. No abstract available.

  PMID: 2308040 BACKGROUND

• Griffin MP, Hansen JW. Can the elimination of lactose from formula improve feeding tolerance in premature infants? J Pediatr. 1999 Nov;135(5):587-92. doi: 10.1016/s0022-3476(99)70057-0.

  PMID: 10547247 BACKGROUND

• Meetze WH, Valentine C, McGuigan JE, Conlon M, Sacks N, Neu J. Gastrointestinal priming prior to full enteral nutrition in very low birth weight infants. J Pediatr Gastroenterol Nutr. 1992 Aug;15(2):163-70. doi: 10.1097/00005176-199208000-00011.

  PMID: 1403464 BACKGROUND

• Reis BB, Hall RT, Schanler RJ, Berseth CL, Chan G, Ernst JA, Lemons J, Adamkin D, Baggs G, O'Connor D. Enhanced growth of preterm infants fed a new powdered human milk fortifier: A randomized, controlled trial. Pediatrics. 2000 Sep;106(3):581-8. doi: 10.1542/peds.106.3.581.

  PMID: 10969106 BACKGROUND

• Schanler RJ. The low-birth weight infant. In: Walker WA, Watkins JB, eds. Nutrition in pediatrics: basic science and clinical application. 2nd ed. Hamilton, Ontario, Canada: BC Decker Inc; 1996. p. 392-412.

  BACKGROUND

• American Academy of Pediatrics Com- mittee on Nutrition. Pediatric Nutrition Handbook. 4th ed. Elk Grove (IL): American Academy of Pediatrics; 1998. p. 69

  BACKGROUND

• Nutrition Committee of the Canadian Pediatric Society. Nutrient needs and feeding of preterm infants. Can Med Assoc J 1995;52:1756-85.

  BACKGROUND

• Sinden AA, Sutphen JL. Dietary treatment of lactose intolerance in infants and children. J Am Diet Assoc. 1991 Dec;91(12):1567-71.

  PMID: 1960350 BACKGROUND

• Carlson SJ, Rogers RR, Lombard KA. Effect of a lactase preparation on lactose content and osmolality of preterm and term infant formulas. JPEN J Parenter Enteral Nutr. 1991 Sep-Oct;15(5):564-6. doi: 10.1177/0148607191015005564.

  PMID: 1942472 BACKGROUND

• Lebenthal E, Lee PC, Heitlinger LA. Impact of development of the gastrointestinal tract on infant feeding. J Pediatr. 1983 Jan;102(1):1-9. doi: 10.1016/s0022-3476(83)80276-5.

  PMID: 6401326 BACKGROUND

• Brady MS, Rickard KA, Fitzgerald JF, Lemons JA. Specialized formulas and feedings for infants with malabsorption or formula intolerance. J Am Diet Assoc. 1986 Feb;86(2):191-200.

  PMID: 3511129 BACKGROUND

• Saavedra JM, Perman JA. Current concepts in lactose malabsorption and intolerance. Annu Rev Nutr. 1989;9:475-502. doi: 10.1146/annurev.nu.09.070189.002355. No abstract available.

  PMID: 2669882 BACKGROUND

• Kien CL. Carbohydrates. In: Tsang RC, Lucas A, Uauy R, et al, eds. Nu- tritional needs of the preterm infant: scientific basis and practical guide- lines. Baltimore (MD): Williams and Wilkins; 1993. p. 47-63.

  BACKGROUND

• Groh-Wargo S. Gastrointestinal development. In: Groh-Wargo S, Thompson M, Hovasi Cox J, Hartline JV, editors. Nutritional care for high risk newborns. Chicago: Precept Press; 2000. p. 209-30.

  BACKGROUND

MeSH Terms

Conditions

Premature Birth; Weight Gain

Interventions

Lactase

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Body Weight Changes; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

beta-Galactosidase; Galactosidases; Glycoside Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes

Study Officials

• Christos Tsakalidis

  Aristotle University Of Thessaloniki

  STUDY DIRECTOR

Central Study Contacts

Dimitrios Rallis

CONTACT

+30231332 3323; drallis@auth.gr

Christos Tsakalidis

CONTACT

+30 2313 323360; tsakalidisx@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor in Pediatrics and Neonatology

Study Record Dates

• First Submitted: August 27, 2025
• First Posted: September 2, 2025
• Study Start: August 27, 2025
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: September 11, 2025

Record last verified: 2025-08

Locations

GR (2)