Hydrolysed Rice Formula Study

A Double-blind, Randomised-controlled Trial Evaluating a Hydrolysed Rice Formula Compared to a Cow's Milk Protein-based Extensively Hydrolysed Formula in Infants With Cow's Milk Allergy

This non-inferiority study aims to determine whether a hydrolysed rice protein formula is as effective as a cow's milk protein based extensively hydrolysed formula using a double-blind, randomised-controlled design over a 28-day intervention period followed by a 2-month follow-up period in infants 0-13 months of age presenting with symptoms/clinical history suggestive of cow's milk allergy. The primary outcome is growth, and secondary outcomes are gastrointestinal tolerance, and differences in intake, allergic symptoms, parental QOL, acceptability, dietary intake, and safety.

Study Overview

• Status: Recruiting
• Conditions: Cow's Milk Protein Allergy
• Intervention / Treatment: Other: Hydrolysed Rice Protein Formula; Other: Cow's Milk Based Extensively Hydrolysed Formula

• Study Type: Interventional
• Enrollment (Estimated): 86
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Isabel Evans, MSc; Phone Number: 07385000738; Email: Isabel.EVANS@danone.com
• Study Contact Backup: Name: Gary P Hubbard, PhD; Phone Number: 07738024720; Email: gary.hubbard@nutricia.com

Study Locations

• United Kingdom
  • Gloucestershire
    • Gloucester, Gloucestershire, United Kingdom, GL1 3NN
      • Recruiting
      • Gloucestershire Royal NHS Trust
      • Contact: Victoria Bittle; Phone Number: 0300 422 5506; Email: v.bittle@nhs.net
  • Somerset
    • Bristol, Somerset, United Kingdom, BS16 1TA
      • Recruiting
      • Bristol Royal Hospital for Children
      • Contact: Sarah Trace; Phone Number: 0117 3428802; Email: sarah.trace@uhbw.nhs.uk

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Male or female
• Aged 0-13 months
• Presenting to primary or secondary care with symptoms/clinical history suggestive of CMA
• Will receive at least 30% of energy requirements from the study formula
• Written informed consent from parent/carer

Exclusion Criteria:

• Severe CMA (including anaphylaxis) and/or requiring an AAF
• Faltering growth (based on NICE guidelines36 - Appendix 1)
• Previous allergy to any study product ingredients (including whey hydrolysate and/or rice)
• Primary lactose intolerance
• Food Protein-Induced Enterocolitis Syndrome (FPIES)
• Exclusively breast fed
• Severe concurrent or chronic disease or genetic syndrome that may impact growth or other outcomes
• Severe hepatic or renal insufficiency
• Premature infants (born <37 weeks) with a corrected age of <4 weeks
• Requirement for any parenteral nutrition
• Participation in other clinical intervention studies within 1 month of recruitment
• Concern around the willingness/ability of the caregiver to comply with the study protocol and/or study requirements

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; Hydrolysed rice protein formula	Other: Hydrolysed Rice Protein Formula; Infants randomised onto this arm will be taking the hydrolysed rice protein formula, with a minimum prescription of 30% of their energy requirements.
Active Comparator: Control; Cow's milk based extensively hydrolysed formula	Other: Cow's Milk Based Extensively Hydrolysed Formula; Infants randomised onto this arm will be taking the control product, with a minimum prescription of 30% of their energy requirements.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Growth	At Baseline (Day 1), End of Intervention (Day 31), and Follow-Up (Day 87) assessments, length and head circumference will be measured using standard measures to the nearest 0.1cm. Body weight (kg) will also be measured, where possible, by the investigating Dietitian/relevant HCP using standard methods to the nearest 0.1kg using a weighing scale without heavy clothing. These measures will be used to calculate z-scores (i.e., weight-for-length, weight, length, and head circumference; based on UK-WHO 2006 growth reference data for children 0-4 years old) and plotted on growth charts for centile measurement.	Baseline to three months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gastrointestinal Tolerance	Gastrointestinal tolerance will be recorded by the parent/carer at Baseline Assessment and Baseline Days 1-3, where this period is undertaken by the patient), during the Intervention Period on Days 10, 17, 24, and 29-31, and during the 2-month Follow-Up period on Days 85-87. Tolerance will be recorded using a standardised GI tolerance questionnaire.	Baseline to three months
Stool frequency and consistency	Stool frequency and consistency (Brussels Infant and Toddler Stool Scale) will be recorded by the parent/carer at Baseline on Days 1-3 (where applicable), as well as on during the Intervention Period on Days 10, 17, 24, and 29-31, and during the 2-month Follow-Up on Days 85-87.	Baseline to three months
Study Product Intake	Intake of study product will be assessed daily throughout the Baseline and Intervention Periods by the parent/carer by recording how much feed was consumed. During the 2-month Follow-Up, intake of study product will be assessed for 3 days (Days 84-87). The daily minimum target intake amount prescribed by the investigating Dietitian/relevant HCP will be recorded at the start of the study, and any changes to this prescription will be noted.	Baseline to three months
Patient Orientated Scoring Atopic Dermatitis Symptoms (PO-SCORAD)	A self-evaluation tool will be completed by the parent/carer on the day of the Baseline Assessment (Day 1), on Days 10 and 31 during the Intervention Period, and on Day 87 during the 2-month Follow-Up to give an indication of severity of atopic dermatitis (where present). This will involve tick box questions and a diagram of an infant for the parent/carer to highlight presence of dermatitis.	Baseline to three months
Patient Reported Atopic Symptoms	The parent/carer will be asked to indicate their perception of the presence and severity of several common atopic symptoms for their child (wheezing, itchy/watery eyes, crying frequency, sneezing/runny/blocked nose, sleep quality) via 100mm visual analogue scales, with 100mm indicating more severe symptoms. These will be recorded on at Baseline Assessment (Day 1), on Day 3, Days 10, 17, 24, and 31 during the Intervention Period, and on Day 87 during the Follow-Up Period.	Baseline to three months
Cow's Milk Related Symptom Score	Infants' stool pattern, the presence and intensity of crying and regurgitation, as well as skin and respiratory manifestations will be assessed via the CoMiSS™ tool by the investigating Dietitian/relevant HCP at the Baseline (Day 1), End of Intervention (Day 31), and Follow-Up (Day 87) Assessments. Total scores range from 0-33, with higher number indicating more severe symptoms of cow's milk allergy.	Baseline to three months
Food Allergy Quality of Life-Parental Burden (FAQL-PB)	Parental measures of QOL (related to their child's allergy) will be assessed via a standardised validated questionnaire on the day of the Baseline Assessment (Day 1), on the final day of the Intervention Period (Day 31), and at the end of the Follow-Up Period (Day 87).	Baseline to three months
Acceptability of the Study Formula	Feed acceptability (e.g., ease of use, liking) will be assessed at Baseline (Day 3, where applicable), during the Intervention Period on Days 10 and 31, and at the end of the Follow-Up period on Day 87, via a Likert-style questionnaire completed by the parent/carer (strongly disagree/disagree/don't know/agree/strongly agree)	Baseline to three months
Nutrient Intake (Energy, Protein, Micronutrients)	Nutrient intake, including intake of all nutrition provided (including the study product, any other enteral feeding, foods, drinks etc.) will be recorded via a 24hr dietary recall conducted by the investigating Dietitian/relevant HCP at the Baseline (Day 1), Day 10, End of Intervention (Day 31), and Follow-Up (Day 87) Assessments. Dietary data will be inputted by the study team into nutritional software to estimate energy and macro- and micronutrient intakes.	Baseline to three months
Dietetic Goal	A dietetic goal (e.g., improve tolerance, reduce atopic symptoms, maintain symptom control, maintain normal growth) will be set by the investigating Dietitian/relevant HCP at the Baseline Assessment (Day 1) for each infant. At the End of Intervention Assessment (Day 31), the investigating Dietitian/relevant HCP will assess and note if the dietetic goal was met (yes/no) and will set a dietetic goal for the Follow-Up Period. At the Follow-Up Assessment (Day 87), the investigating Dietitian/relevant HCP will assess and note if the dietetic goal was met (yes/no).	Baseline to three months
Overall Safety	All adverse events will be recorded throughout the study.	Through study completion, an average of three months

Collaborators and Investigators

• Sponsor: Nutricia UK Ltd

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2024
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: February 1, 2024
• First Submitted That Met QC Criteria: February 23, 2024
• First Posted (Estimated): March 1, 2024

Study Record Updates

• Last Update Posted (Estimated): March 1, 2024
• Last Update Submitted That Met QC Criteria: February 23, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Food Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Milk Hypersensitivity
• Other Study ID Numbers: HRF2023

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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