A Community-based Assessment of Skin Care, Allergies, and Eczema (CASCADE)

Atopic dermatitis (AD) affects over 9 million children in the U.S. and often heralds the development of asthma, food allergy, skin infections and neurodevelopmental disorders. Recent advances identify skin barrier dysfunction to be the key initiator of AD and possibly allergic sensitization.

Our central hypothesis is that daily emollient use from birth can prevent the development of AD in a community setting and into newborns unselected for risk. The results of a community-based clinical trial utilizing a pragmatic trial design will be immediately applicable to the population at large and will establish a new standard of care for all newborns.

Study Overview

• Status: Active, not recruiting
• Conditions: Eczema; Atopic Dermatitis; Atopic Eczema; Atopic Disorders
• Intervention / Treatment: Other: Participant choice of over-the-counter emollients: Vaseline, Vanicream, CeraVe Healing Ointment, CeraVe cream, Cetaphil cream

Detailed Description

AD affects over 9 million children in the U.S. and ranks first among all skin conditions in global disability burden. AD often heralds the development of several comorbidities including asthma, food allergy, skin infections and neurodevelopmental disorders. Because of the significant socioeconomic impact of atopic dermatitis and its effect on the quality of life of children and families, there have been decades of research focused on prevention with limited success. Recent advances in cutaneous biology identify epidermal defects and skin barrier dysfunction to be the key initiators of atopic dermatitis and possibly allergic sensitization. Our central hypothesis is that emollient therapy from birth can prevent the development of AD. The findings of this trial will support the development of evidence-based skin care clinical guidelines for infants that currently do not exist. Recently, our international multi-centered clinical trial found enhancing early skin barrier function with daily emollient use from birth significantly reduces the risk of AD development in high-risk populations by 50%. With CASCADE, we extend this work into the community setting and into newborns unselected for risk, so results will be immediately applicable to the population at large and will establish a new standard of care for all newborns.

The specific aims are as follows:

1. Perform a community-based pragmatic randomized controlled trial investigating whether daily full-body emollient application starting in the first 2 months of life prevents atopic dermatitis in a real-world setting. The population for this trial consists of newborns between 0-2monthsof age, not selected for risk. Recruitment of families will occur during the course of routine care within primary care offices that are members of practice-based research networks(PBRNs).The intervention includes general skin care recommendations plus full-body daily lipid-rich emollient use. The control population will receive general skin care advice only and refrain from daily emollient use. The primary outcome will be the cumulative incidence of atopic dermatitis at age 24 months as determined by blinded clinicians trained in the diagnosis of AD. Key secondary clinical outcomes include time to disease onset and incidence of self-reported food allergy and wheeze using parental questionnaires.
2. As an exploratory aim, determine whether a family history of allergic disease and key early life exposures such as pet ownership modify the preventive effect of emollient therapy on atopic dermatitis. While the primary objective of this clinical trial is to determine the effectiveness of an emollient intervention in a real-world setting, data will be gathered on allergy history in the family and pet ownership-variables that may modify the effect of emollient therapy. Future implementation studies may target subpopulations found most likely to benefit from emollient intervention.

Twenty-five primary care clinics that participate in PBRNs from Oregon, Colorado, Wisconsin and North Carolina are the setting for the study protocol. The expected results from this project would represent a major public health breakthrough with the potential for reducing the atopic disease burden on a global scale.

• Study Type: Interventional
• Enrollment (Actual): 1250
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80045
      • University of Colorado-Denver
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Wisconsin
    • Madison, Wisconsin, United States, 53175
      • University of Wisconsin-Madison

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 2 months (Child)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Parent can provide electronic signed and dated informed consent form.
• Parent is willing and able to comply with all study procedures for the duration of the study.
• Parent is a primary caretaker of an infant 0 to 2 months of age.
• Parent is 18 years of age or older at time of consent.
• Parent can speak, read, and write in English or Spanish.
• Parent has a valid e-mail address or phone that can receive text messages
• Parent has reliable access to the internet.
• Infant is a patient of a participating Meta-LARC clinic site at the time of consent.

Exclusion Criteria:

• Infant was born at less than 25 weeks gestational age.
• Infant has established eczema as diagnosed by the primary healthcare provider at clinic site of enrollment per parent report.
• Infant has known adverse reaction to petrolatum-based emollients.
• Infant has an immunodeficiency genetic syndrome such as Wiskott-Aldrich Syndrome or Severe Combined Immunodeficiency Syndrome.
• Infant has extremely low birth weight (less than 1000g or 2.2 lbs at birth).
• Infant has a sibling enrolled in the study.
• Parent is unwilling or unable to comply with study procedures.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Daily Emollient; Parents assigned to the intervention arm will receive a lipid-rich emollient and educational materials promoting once daily full-body emollient use until their infant is 24 months old. Parents will select one of five emollients to be mailed to the dyad's home at enrollment and approximately every six months for the duration of the study. These emollients include (1) CeraVe Healing Ointment, (2) Vaseline, (3) Cetaphil cream, (4) CeraVe cream, and (5) Vanicream.	Other: Participant choice of over-the-counter emollients: Vaseline, Vanicream, CeraVe Healing Ointment, CeraVe cream, Cetaphil cream; Lipid-rich emollient serving as skin barrier
No Intervention: Natural Skin; Parents assigned to the control arm will receive educational materials promoting general infant skin care guidelines only and will be asked to refrain from emollient use unless dry skin develops (current standard of care guidelines).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative incidence of provider-diagnosed AD	The cumulative incidence of AD at 24 months of age as recorded in health records. Trained clinicians will assess for AD at each clinic visit and record in the health record.	up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Parental report of AD	Parental report of provider-diagnosed AD	up to 24 months
AD by UK Working Party criteria	Parental report of AD using UK Working Party criteria	up to 24 months
AD by Children's Eczema Questionnaire	AD as diagnosed by the Children's Eczema Questionnaire (CEQ)	up to 24 months
Prescription or over-the-counter therapies for AD	Cumulative incidence of provider-diagnosed AD requiring prescription or over-the-counter therapies from chart review	up to 24 months
Skin infections detected in chart review	Chart outcome for provider diagnosis or medications associated with skin infections, including topical antibiotics	up to 24 months
Sleep loss	Parental report of sleep loss of the infant reported as average number of days per week (1 week recall) of disrupted sleep in their infant [single item of IDQoL]	12 and 24 months
Prescribed topical skin medication	Any steroidal or non-steroidal cream or ointment, recorded by parent or recorded from records review. Evaluated in (1) all children and (2) those with AD only.	up to 24 months
Provider-diagnosed asthma	Asthma diagnosis from chart review	up to 24 months
Asthma risk	Asthma risk using a modification of the Asthma Predictive Index	up to 24 months
Food allergy symptoms	Parental report of immediate food allergy symptoms	up to 24 months
Reported diagnosis of food allergy	Parental report of a provider diagnosis of food allergy that was confirmed by prick testing or IgE blood test	up to 24 months
Severity of AD symptoms using POEM	In infants who develop AD, symptom severity as reported in the patient-oriented eczema measure (POEM) instrument	up to 24 months
Severity of AD symptoms using IDQoL	In infants who develop AD, symptom severity as reflected by the Infant Dermatology Quality of Life Instrument (IDQOL)	up to 24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Delayed onset of AD	Is the earliest evidence of diagnosis of AD (parent report or chart review) earlier in one study arm or the other?	3 months - 1 year
Primary and secondary outcomes at 12 months	Primary and secondary outcomes evaluated at 12 months (rather than 24) time frame	up to 12 months
Age at onset	Parental report of eczema from quarterly contacts or annual questionnaires or provider-recorded date of first diagnosis retrieved from record review of chart indexed to the nearest quarter of follow-up	up to 24 months
AD risk	Subpopulation analysis: interaction of treatment and having a family history of atopy in a first-degree relative	up to 24 months
Interaction of treatment and climate	Subpopulation analysis: interaction of treatment and living in a dry climate using the average relative humidity over a year in the clinic's locality in records from the National Climate Data Center and Weather Service	up to 24 months
Interaction of treatment and pets	Subpopulation: interaction of treatment and having pets or regular contact with farm animals in early childhood	up to 24 months
Effect of CeraVe	Effect of CeraVe cream or ointment compared to other emollients or controls	up to 24 months
Age of initiation	Baby's age at randomization (as proxy for initiation of emollient use) as moderator of treatment effect	up to 24 months
Bathing interaction	Frequency of bathing (days per week) interaction with treatment effect	up to 24 months
Caesarean birth interaction	Caesarean birth interaction with treatment effect	up to 24 months
Baby's sex	Subpopulation: Sex of baby	up to 24 months
Baby's race	Subpopulation: Race of baby	up to 24 months
Baby's ethnicity	Subpopulation: Ethnicity of baby	up to 24 months
Incidence of AD at 18 months	Multivariate or latent variable analysis to estimate cumulative incidence in each treatment arm using multiple candidate definitions and estimating the correlations between the definitions	up to 18 months

Collaborators and Investigators

• Sponsor: Oregon Health and Science University
• Collaborators: University of Colorado, Denver; University of Wisconsin, Madison; Duke University
• Investigators: Principal Investigator: Eric Simpson, MD, Oregon Health and Science University

Publications and helpful links

General Publications

• Eichner B, Michaels LAC, Branca K, Ramsey K, Mitchell J, Morris CD, Fagnan LJ, Dolor RJ, Elder N, Hahn DL, Nease DE, Lapidus J, Cibotti R, Block J, Simpson EL. A Community-based Assessment of Skin Care, Allergies, and Eczema (CASCADE): an atopic dermatitis primary prevention study using emollients-protocol for a randomized controlled trial. Trials. 2020 Mar 4;21(1):243. doi: 10.1186/s13063-020-4150-5.

Study record dates

Study Major Dates

• Study Start (Actual): July 3, 2018
• Primary Completion (Actual): September 29, 2023
• Study Completion (Estimated): February 28, 2025

Study Registration Dates

• First Submitted: January 11, 2018
• First Submitted That Met QC Criteria: January 17, 2018
• First Posted (Actual): January 24, 2018

Study Record Updates

• Last Update Posted (Actual): April 3, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Prevention; Emollient; Pragmatic clinical trial
• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Genetic; Hypersensitivity; Skin Diseases, Eczematous; Dermatitis; Eczema; Dermatitis, Atopic; Dermatologic Agents; Petrolatum; Emollients
• Other Study ID Numbers: 1R01AR071057-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data sharing will be according to the NIAMS guidelines
• IPD Sharing Time Frame: Supporting information will be shared per NIAMS guidelines
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

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