## Protocol Section
### Identification Module
**NCT ID:** NCT02785679

**Brief Title:** The Influence of Early and Continuous Exposure of Infants to Cow's Milk Formula on the Prevention of Milk Allergy

**Official Title:** The Influence of Early and Continuous Exposure of Infants to Cow's Milk Formula on the Prevention of Milk Allergy

#### Organization Study ID Info
**ID:** 011-16-MMC
#### Organization
**Class:** OTHER
**Full Name:** Meir Medical Center
### Status Module
#### Completion Date
**Date:** 2021-12-31

**Type:** ESTIMATED

#### Expanded Access Info
**Last Known Status:** RECRUITING
#### Last Update Post Date
**Date:** 2021-04-14

**Type:** ACTUAL

**Last Update Submit Date:** 2021-04-13

**Overall Status:** UNKNOWN

#### Primary Completion Date
**Date:** 2021-08-31

**Type:** ESTIMATED

#### Start Date
**Date:** 2018-03-20

**Type:** ACTUAL

**Status Verified Date:** 2021-04

#### Study First Post Date
**Date:** 2016-05-30
**Type:** ESTIMATED
**Study First Submit Date:** 2016-05-25
**Study First Submit QC Date:** 2016-05-27
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** Schneider Children's Hospital

#### Lead Sponsor

**Class:** OTHER

**Name:** Meir Medical Center

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** Cow's milk protein (CMP) allergy is one of the most common food allergies and potentially a fatal one. Early feeding with CMP has been considered in the past as a risk factor for development of CMP allergy in high risk infants. Although other studies argue with this assumption and suggest early exposure to CMP might be protective against atopic dermatitis and CMP allergy. A cohort study that first introduction of CMP after 15-30 days of age, raised the risk for CMP allergy.The aim of this study is to investigate if early and continuous exposure to CMF will decrease CMP allergy rate.

**Detailed Description:** Background: Cow's milk protein (CMP) allergy is one of the most common food allergies and potentially a fatal one. The incidence of milk allergy is 1.5-3% in the first year of life, but only 60% of the reactions are IgE mediated. CMP allergy tends to resolve in approximately 45-50% of the infants at 1 year of age, in 60-75% at the age of 2, and 85-90% at 3 years. The range for IgE mediated CMP allergy is 29-76%. A recent study suggested that the natural history of CMP allergy might have changed over time, with slower rates of resolution and a higher proportion of children with disease persisting into adolescence and adulthood. In the past it has been described that there is more incidence of CMP allergy in children from families with positive history of allergy. Early feeding with CMP has been considered in the past as a risk factor for development of CMP allergy in high risk infants. Although other studies argue with this assumption and suggest early exposure to CMP might be protective against atopic dermatitis and CMP allergy. A cohort study that first introduction of CMP after 15-30 days of age, raised the risk for CMP allergy. A recent study on peanut allergy found that continuous early exposure to peanut dramatically decreased the incidence of peanut allergy. The research in the field of food allergy and especially in CMP allergy is very alert those days. But as far as the investigators knowledge, there are no prospective studies from the first days of life that examined the influence of early and continuous exposure to cow's milk formula (CMF) on CMP allergy. The existing data related to CMP allergy is controversial and inconclusive. Thus, no one can rely on it to establish clear recommendations for parents when is the best time to combine CMF in the infants diet. Working hypothesis and aims: The aim of the study is to investigate if early and continuous exposure to CMF will decrease CMP allergy rate. The investigators assumption is that the rate of CMP allergy in the intervention groups and in infants who are only feed by CMF, will be lower than in the group of infants who are exclusively breast feed. Methods: Recruitment of 2,500 infants from first day of life and divide the participants into 4 groups: 1. Exclusive breast feeding. 2. Exclusive CMF feeding. 3. Breast feeding with 20 cc of CMF per day. 4. Breast feeding with one meal per day of CMF. The mother will complete a survey questionnaire before the labor. Infants will be followed for 1 year. During this follow-up period -the participants will be examined by an allergologist at the age of 2 month and 1 year. In between, the infants will be followed by a phone questionnaire once in a month. Specific CM IgE analysis from umbilical cord blood and skin test at 2 month of age will be performed. Inclusion criteria - Term and near term newborns (gestational age of at least 36 weeks), normal birth weight, normal perinatal follow-up and without congenital defects. Expected results: The rate of CMP allergy in the intervention groups and in the group on exclusively CMF feeding will be lower than in the group on exclusive breast feeding. Importance: If the investigators will be able to prove the study hypothesis (and even if not), it will have a significant influence on the diet recommendations for infants. Probable implications to Medicine: If the investigators will get the expected results, the recommendations that exist today for infant's feeding can be changed.

### Conditions Module

**Conditions:**

- Cow Milk Allergy

- Newborns

**Keywords:**

- Allergy

- Cow's milk

- breast feeding

- Cow's milk formula

- prevention

### Design Module

#### Design Info

**Allocation:** NON_RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** PREVENTION

#### Enrollment Info

**Count:** 2500

**Type:** ESTIMATED

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Exclusive breast feeding

**Label:** Exclusive breast feeding

**Type:** NO_INTERVENTION

#### Arm Group 2

**Description:** Exclusive CMF feeding

**Label:** Exclusive CMF feeding

**Type:** NO_INTERVENTION

#### Arm Group 3

**Description:** Breast feeding with addition (as intervention) of 20 cc of cow's milk formula (CMF) per day

**Intervention Names:**

- Dietary Supplement: cow's milk formula

**Label:** Breast feeding with small amount of CMF

**Type:** ACTIVE_COMPARATOR

#### Arm Group 4

**Description:** Breast feeding with addition (as intervention) of one meal per day of cow's milk formula (CMF)

**Intervention Names:**

- Dietary Supplement: cow's milk formula

**Label:** Breast feeding with one meal of CMF

**Type:** ACTIVE_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Breast feeding with one meal of CMF

- Breast feeding with small amount of CMF

**Description:** addition of cow's milk formula in two different dosage - one only 20ml per day and one group a full meal per day

**Name:** cow's milk formula

**Type:** DIETARY_SUPPLEMENT

### Outcomes Module

#### Primary Outcomes

**Description:** Measure the rate of cow's milk allergy infants in each group and compare the rate of allergy between the groups.

**Measure:** The incidence of cow's milk allergy in the intervention groups

**Time Frame:** 1 year

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Term and near term newborns (gestational age of at least 36 weeks)
* normal birth weight
* normal perinatal follow-up (physiological neonatal jaundice is not an exclusion criteria)
* without congenital defects

Exclusion Criteria:

* Preterm newborns
* Congenital defects
* Newborn suffering from acute event

**Healthy Volunteers:** True

**Maximum Age:** 2 Days

**Minimum Age:** 2 Hours

**Sex:** ALL

**Standard Ages:**

- CHILD

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** idit.roth@clalit.org.il

**Name:** Idit Lachover- Roth, MD

**Phone:** 972-9-7472320

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Kfar Saba

**Contacts:**

***Contact 1:***

- **Email:** idit.roth@clalit.org.il

- **Name:** Idit Lachover - Roth, MD

- **Phone:** 972-54-3152585

- **Role:** CONTACT

**Country:** Israel

**Facility:** Meir medical center

**Status:** RECRUITING

#### Overall Officials

**Official 1:**

**Affiliation:** allergy and immunology unit, MeirMc

**Name:** Ronit Confino- Cohen, MD

**Role:** STUDY_DIRECTOR

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000007154

- Term: Immune System Diseases

- ID: D000005512

- Term: Food Hypersensitivity

- ID: D000006969

- Term: Hypersensitivity, Immediate

### Condition Browse Module - Browse Branches

- Abbrev: BC20

- Name: Immune System Diseases

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M10018

- Name: Hypersensitivity

- Relevance: HIGH

- As Found: Allergy

- ID: M18719

- Name: Milk Hypersensitivity

- Relevance: HIGH

- As Found: Milk Allergy

- ID: M10200

- Name: Immune System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M8636

- Name: Food Hypersensitivity

- Relevance: LOW

- As Found: Unknown

- ID: M10020

- Name: Hypersensitivity, Immediate

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000006967

- Term: Hypersensitivity

- ID: D000016269

- Term: Milk Hypersensitivity

### Misc Info Module

- Version Holder: 2024-05-24
