Amino Acid Supplementation in Children with Stunting

Official title

Efficacy of Amino Acid Supplementation on Gut Function and Nutritional Status in FIlipino Children Below Three Years Old

Overview

The goal of this intervention study is to determine the effects of indispensable amino acid (IAA) supplementation on children of either sex, aged 18 to 36 months. The main questions it aims to answer are: * Does IAA supplementation affect biomarkers of Environmental Enteric Dysfunction (EED), through the Dual Sugar Lactulose/Rhamnose (L/R) test, plasma intestinal fatty acid binding protein, plasma lipopolysaccharide binding protein, fecal myeloperoxidase, fecal neopterin, and gut microbiota? * Does IAA supplementation impact amino acid digestion, as assessed by a dual-stable isotope tracer? * What is the weight gain and the changes in length-for-Age z-scores (LAZ) and body composition? The researchers will compare the effects of consumption of standard complementary food with added IAA against a control group that has no added IAA through the assessment of the various biomarkers. Participants will: * answer questions regarding personal, demographic, anthropometric, and food intake information. * provide biological samples, including breath, urine, stool, blood, and saliva. * consume solutions or meals that contain sugars and/or stable isotope tracers. * visit the FNRI and receive house visits by study staff. * consume complementary food with or without supplement daily for 28 days.

Detailed description

Protocol treatment will start within two weeks of enrollment to the study. Following the baseline study assessments, each participant will receive the standard complementary foods (in the control group) or standard complementary foods supplemented with IAAs (histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine) (in the intervention group).

Standard complementary foods will be comprised of ingredients mainly of rice and legumes. Standard complementary foods are foods that meet the dietary needs of children 6-36 months of age.

At least three observed (controlled) feeding sessions per week will be conducted over the 4 weeks of the study to confirm that the entire supplement was consumed or confirm intake. The observed feeding will take place at the child's home or at the barangay center. Uptake on non-observed days will be based on the caregiver's report. On each intervention monitoring day, a questionnaire will also be administered to assess child morbidity that day and on the day prior. A pediatrician or an alternate medical practitioner will also be invited during the data collection where in stable isotopes will be administered. The duties and responsibilities of the physician include: medical assessment of the participant, assistance in the collection of blood samples, assessment of adverse events (if any), and provision of first aid (if needed).

In the absence of treatment delays due to adverse events, the intervention will continue for 1 month or until one of the following criteria apply:

* Child is not able to tolerate the supplement (throws up) * Severe acute malnutrition (SAM) * Inter-current illness that prevents further administration of treatment * Unacceptable adverse event(s) * Study participant voluntarily withdraws from treatment OR * Other general or specific changes in the study participant's condition render the study participant unacceptable for further treatment in the judgment of the investigator.

For each participant, tests to be conducted at study enrolment will be spread over three days. At the end of the study, endline tests will be spread over 2 days. Baseline visits for breath, blood, urine, and fecal collection should be conducted within -3 days prior to study treatment (day 3) while endline visits should be conducted within +7 days of study treatment (day 31). The intervention will be provided in coded sachets, distributed as per convenient for local custom to best ensure compliance with a minimum of three supervised feeds per week to ensure supplement is consumed at least periodically by the child and also to assess compliance.

Interventions

• Dietary supplement IAA mix supplement
  The intervention is a daily IAA dose that provides x1.5 the estimated average requirement (EAR) for a healthy child. This IAA dose will be mixed to the complementary food and will be taken once daily for 4 weeks (28 days) by the child in the intervention group.
• Other Complementary food comprised of rice and legumes
  Each study child will receive standard complementary food which he/she will take once daily for 4 weeks (28 days)

Primary outcome measures

• Change from Baseline in the Gut Permeability as Assessed by the Lactulose/Rhamnose (L/R) Test at 28 days [Time frame: Baseline and end of intervention at 28 days]

Secondary outcome measures (6)

• Change from Baseline in Protein Absorption as Assessed by the Dual Stable Isotope Tracer (DSIT) Technique at 28 days [Time frame: Baseline and end of intervention at 28 days]
• Change from Baseline in Gut Digestive Capacity Measured by the 13C-Sucrose Breath Test (SBT) at 28 days [Time frame: Baseline and end of intervention at 28 days]
• Change from Baseline in Gut Function Based on Plasma LPS-Binding Protein (LPSBP) Concentration at 28 days [Time frame: Baseline and end of intervention at 28 days]
• Change from Baseline in Gut Function Based on Intestinal Fatty Acid Binding Protein (iFABP) Concentration at 28 days [Time frame: Baseline and end of intervention at 28 days]
• Change from Baseline in Gut Inflammation Based on Fecal Myeloperoxidase Concentration at 28 days [Time frame: Baseline and end of intervention at 28 days]
• Change from Baseline in Gut Inflammation Based on Fecal Neopterin Concentration at 28 days [Time frame: Baseline and end of intervention at 28 days]

Eligibility criteria

Inclusion criteria

• 18 to 36 months old (of either sex)
• Stunted (LAZ of less than -2)
• Parent, caregiver or guardian able and willing to give written, informed consent

Exclusion criteria

• Wasted (WHZ of less than -2)
• Overweight (WHZ of more than 2)
• Have had diarrhea (by self-report) in the preceding month
• Sibling or twin of another participating study child (2 children of different families in the same household are both eligible)
• Have taken antibiotics in the preceding month
• Have food allergies/intolerance
• Had a serious illness within the last three (3) months or have any underlying condition which in the opinion of the pediatrician would put the subject at undue risk of failing study completion or would interfere with analysis of study results

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Philippines · 1 center

• Department of Science and Technology - Food and Nutrition Research Institute — City of Taguig

Publications

• Abtahi S, Sailer A, Roland JT, Haest X, Chanez-Paredes SD, Ahmad K, Sadiq K, Iqbal NT, Ali SA, Turner JR. Intestinal Epithelial Digestive, Transport, and Barrier Protein Expression Is Increased in Environmental Enteric Dysfunction. Lab Invest. 2023 Apr;103(4):100036. doi: 10.1016/j.labinv.2022.100036. Epub 2023 Jan 10. PMID 36870290
• Antiporta DA, Ambikapathi R, Bose A, Maciel B, Mahopo TC, Patil C, Turab A, Olortegui MP, Islam M, Bauck A, McCormick B, Caulfield LE; MAL-ED Network Investigators. Micronutrient intake and the probability of nutrient adequacy among children 9-24 months of age: results from the MAL-ED birth cohort study. Public Health Nutr. 2021 Jun;24(9):2592-2602. doi: 10.1017/S1368980020000877. Epub 2020 Jul 2. PMID 32611463
• Arnold BF, Null C, Luby SP, Unicomb L, Stewart CP, Dewey KG, Ahmed T, Ashraf S, Christensen G, Clasen T, Dentz HN, Fernald LC, Haque R, Hubbard AE, Kariger P, Leontsini E, Lin A, Njenga SM, Pickering AJ, Ram PK, Tofail F, Winch PJ, Colford JM Jr. Cluster-randomised controlled trials of individual and combined water, sanitation, hygiene and nutritional interventions in rural Bangladesh and Kenya: t PMID 23996605
• Arsenault JE, Brown KH. Effects of protein or amino-acid supplementation on the physical growth of young children in low-income countries. Nutr Rev. 2017 Sep 1;75(9):699-717. doi: 10.1093/nutrit/nux027. PMID 28938793
• Budge S, Parker AH, Hutchings PT, Garbutt C. Environmental enteric dysfunction and child stunting. Nutr Rev. 2019 Apr 1;77(4):240-253. doi: 10.1093/nutrit/nuy068. PMID 30753710
• Capanzana MV, Aguila DV, Gironella GMP, Montecillo KV. Nutritional status of children ages 0-5 and 5-10 years old in households headed by fisherfolks in the Philippines. Arch Public Health. 2018 Apr 16;76:24. doi: 10.1186/s13690-018-0267-3. eCollection 2018. PMID 29686867
• Denno DM, VanBuskirk K, Nelson ZC, Musser CA, Hay Burgess DC, Tarr PI. Use of the lactulose to mannitol ratio to evaluate childhood environmental enteric dysfunction: a systematic review. Clin Infect Dis. 2014 Nov 1;59 Suppl 4:S213-9. doi: 10.1093/cid/ciu541. PMID 25305289
• Devi S, Varkey A, Sheshshayee MS, Preston T, Kurpad AV. Measurement of protein digestibility in humans by a dual-tracer method. Am J Clin Nutr. 2018 Jun 1;107(6):984-991. doi: 10.1093/ajcn/nqy062. PMID 29771297

Identifiers

NCT: NCT06676215 · FIERC-2023-004

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗