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

• ClinicalTrials.gov Identifier: NCT03409367
• Recruitment Status: Active, not recruiting
• First Posted: January 24, 2018
• Last Update Posted: April 30, 2021
• Sponsor: Oregon Health and Science University
• Collaborators: University of Wisconsin, Madison; University of Colorado, Denver; Duke University
• Information provided by (Responsible Party): Eric Simpson, Oregon Health and Science University

Tracking Information

• First Submitted Date: January 11, 2018
• First Posted Date: January 24, 2018
• Last Update Posted Date: April 30, 2021
• Actual Study Start Date: July 3, 2018
• Estimated Primary Completion Date: May 8, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 17, 2018)

Cumulative incidence of AD [ Time Frame: 24 months ]

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 17, 2018)

• Parental report [ Time Frame: 3, 6, 9, 12, 15, 18 and 24 months ]
  Parental report of provider-diagnosed AD
• Children's Eczema Questionnaire [ Time Frame: 12 and 24 months ]
  AD as diagnosed by the Children's Eczema Questionnaire (CEQ)
• Sleep loss [ Time Frame: 12 and 24 months ]
  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
• Prescription topical skin medication [ Time Frame: 3, 6, 9, 12, 15, 18, 21 and 24 months ]
  Any prescription topical medication use or over-the-counter hydrocortisone usage recorded by parent or recorded from records review
• Asthma risk [ Time Frame: 12 and 24 months ]
  Asthma risk using a modification of the Asthma Predictive Index
• Food allergy symptoms [ Time Frame: 12 and 24 months ]
  Parental report of immediate food allergy symptoms
• Food allergy clinician diagnosed [ Time Frame: 12 and 24 months ]
  Parental report of a provider diagnosis of food allergy that was confirmed by prick testing or IgE blood test
• Global Health Status [ Time Frame: 12 and 24 months ]
  Global Health Status using one question from the PROMIS Pediatric Global Health (PGH-7) instrument
• Atopic dermatitis severity 1 [ Time Frame: 12 and 24 months ]
  In infants who develop AD: (1)Time to onset of AD as measured by parental report of eczema age of onset
• Atopic dermatitis severity 2 [ Time Frame: 12 and 24 months ]
  In infants who develop AD: (2) Time to onset of AD as measured by provider-recorded date of first diagnosis retrieved from record review of health record
• Atopic dermatitis severity 3 [ Time Frame: 12 and 24 months ]
  In infants who develop AD: (3) AD symptom severity as reported by the patient-oriented eczema measure (POEM) instrument
• Atopic dermatitis severity 4 [ Time Frame: 12 and 24 months ]
  In infants who develop AD: (4) Parent-reported global severity of eczema assessment
• Atopic dermatitis severity 5 [ Time Frame: 12 and 24 months ]
  In infants who develop AD: (5) Infant Dermatology Quality of Life Instrument (IDQOL)

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Community-based Assessment of Skin Care, Allergies, and Eczema
• Official Title: A Community-based Assessment of Skin Care, Allergies, and Eczema

Brief Summary

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.

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
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Single Group Assignment
Intervention Model Description:

This is a pragmatic, multi-site, randomized community-based trial in which dyads of a parent or legal guardian ("parent") and an infant age 0 to 2 months are enrolled. Participating dyads are randomly assigned to receive lipid-rich emollient with web-based instructions for daily use to infants plus routine skin care instructions (every day moisturizer group) or routine skin care instructions alone (natural skin group). Both groups will receive e-mail and text message reminders to follow protocol instructions based on their group allocation until the infant reaches 24 months old.

Masking: Triple (Care Provider, Investigator, Outcomes Assessor)
Masking Description:

Due to the nature of the intervention, it is not possible blind dyads to the intervention. Administering a placebo emollient is impossible as there are no active ingredients in the emollient and using an emollient that has no barrier improvement properties may irritate the skin. The clinician completing the final assessment will be a blinded assessor.

Clinic staff will not be informed of participant enrollment or study arm. Parents will be instructed not to disclose their treatment group to clinic staff. Clinicians and clinic staff will direct participants to follow skin care recommendations as described by the study materials.

Blinded researchers will be responsible for health record review to collect the primary outcome. At completion of health record review, researchers will complete a form measuring whether the assessor became unblinded while reviewing the record.

Primary Purpose: Prevention

Condition

• Atopic Dermatitis
• Atopic Disorders
• Eczema
• Atopic Eczema

Intervention

Other: Participant choice of over-the-counter emollients: Vaseline, Vanicream, CeraVe Healing Ointment, CeraVe cream, Cetaphil cream

Lipid-rich emollient serving as skin barrier

Study Arms

• 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.
  Intervention: Other: Participant choice of over-the-counter emollients: Vaseline, Vanicream, CeraVe Healing Ointment, CeraVe cream, Cetaphil cream
• 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).

• 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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: January 17, 2018): 1250
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 31, 2024
• Estimated Primary Completion Date: May 8, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 0 Days to 63 Days (Child)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03409367
• Other Study ID Numbers: 1R01AR071057-01A1( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Data sharing will be according to the NIAMS guidelines
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Time Frame: Supporting information will be shared per NIAMS guidelines

• Current Responsible Party: Eric Simpson, Oregon Health and Science University
• Original Responsible Party: Eric Simpson, Oregon Health and Science University, Associate Professor
• Current Study Sponsor: Oregon Health and Science University
• Original Study Sponsor: Same as current

Collaborators

• University of Wisconsin, Madison
• University of Colorado, Denver
• Duke University

Investigators

• Principal Investigator: Eric Simpson, MD; Oregon Health and Science University

• PRS Account: Oregon Health and Science University
• Verification Date: April 2021