Clinical trial NCT06750653: Skin Barrier Function and Inflammation in Aging: The BIA Study
Official title: Skin Barrier Function and Inflammation in Aging: The BIA Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Inflammation
Skin Inflammation
Aging
Keywords: CeraVe
Vaseline
Aging
Inflammation
Skin
Older Adults
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
First posted: 2024-12-27
Enrollment: 32
Sex: ALL
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Subjects will act as their own control - they will be asked to apply the study moisturizer they are randomized to for one intervention period (4 weeks) and not to apply topical moisturizers for the other 4- week intervention period).
Primary purpose: TREATMENT

Brief summary: This is a randomized, investigator-blinded, self-controlled pilot study of the physiologic response to topical moisturizers among older adults with dry skin. The overarching hypothesis is that skin barrier decline is an important source of chronic inflammation, and that skin barrier restoration with moisturizers can reduce serum biomarkers of inflammation. The primary objective is to determine the feasibility for a larger trial, and the secondary objectives are to determine the extent to which measures of serum inflammation, skin barrier function, and the skin microbiome change in response to moisturizers. Participants will be asked to apply one of two topical moisturizers that are widely available over the counter in the US (Vaseline® 100% pure petroleum jelly or CeraVe® moisturizing cream) once daily for 4 weeks to the front of the torso, buttocks, arms, and legs. Subjects will act as their own control (i.e. they will be asked to apply the study moisturizer they are randomized to for one intervention period (4 weeks) and not to apply topical moisturizers for the other 4- week intervention period). Participants will be randomized in a 1:1:1:1 ratio to one of 4 treatment groups: i. no intervention then CeraVe; ii. CeraVe then no intervention; iii. no intervention then Vaseline; iv. Vaseline then no intervention. At each visit (baseline, week 4, and week 8), participants will undergo skin barrier testing, skin microbiome sampling, and phlebotomy to measure serum inflammatory markers.

Detailed description: In older adults, inflammation is associated with geriatric conditions, including multimorbidity and frailty, that result in premature death. This phenomenon has been termed 'inflammaging,' and multiple potential mechanisms have been identified, including chronic infections, visceral obesity, increased gut permeability, and cellular senescence, among others.1,2 Limited data suggest that age-associated barrier decline in the skin may also play an important role. Beginning at about age 50, skin barrier decline is caused by decreased Na+/H+ antiporter activity and impaired stratum corneum acidification.3 Persons \>70 years of age also suffer from additional defects in cutaneous lipid production.4 The result is reduced resilience to minor injury and epidermal cytokine generation, which may have significant systemic effects, given that the skin is the body's largest organ.5 Additionally, changes in the skin barrier may result in dysbiosis and increased exposure to microbial products, as has been seen in age-associated gut barrier decline.6 Skin barrier decline has been directly correlated with levels of keratinocyte-derived inflammatory markers in aged mice.7 Furthermore, there is experimental evidence that application of moisturizers to aged skin may improve skin barrier function and reduce inflammation. In aged mice, application of petrolatum twice daily for 10 days significantly reduced cutaneous and serum inflammatory cytokines including TNFalpha, IL-1alpha, IL-1beta, and IL-6 after minor injury.7 The investigators propose a randomized, investigator-blinded, self-controlled pilot study of the physiologic response to topical moisturizers among older adults with dry skin. The overarching hypothesis is that skin barrier restoration with moisturizers can reduce serum biomarkers of inflammation. The primary objective is to determine the feasibility for a larger trial, and the secondary objectives are to determine the extent to which measures of serum inflammation, skin barrier function, and the skin microbiome change in response to moisturizers. Participants will be asked to apply one of two topical moisturizers that are widely available over the counter in the US (Vaseline® 100% pure petroleum jelly or CeraVe® moisturizing cream) once daily for 4 weeks to the front of the torso, buttocks, arms, and legs. Subjects will act as their own control (i.e. they will be asked to apply the study moisturizer they are randomized to for one intervention period (4 weeks) and not to apply topical moisturizers for the other 4- week intervention period). Participants will be randomized in a 1:1:1:1 ratio to one of 4 treatment groups: placebo i. no intervention then CeraVe; ii. CeraVe then no intervention; iii. no intervention then Vaseline; iv. Vaseline then no intervention. At each visit (baseline, week 4, and week 8), participants will undergo skin barrier testing, skin microbiome sampling, and phlebotomy to measure serum inflammatory markers.

Eligibility criteria: Inclusion Criteria

1. Male or female ≥ 70 years of age at the baseline visit.
2. Diagnosis of xerosis cutis based on an Overall Dry skin (ODS) score of =\> 1 for any body site where patients will be asked to apply moisturizer (i.e. arms, legs, buttocks, front of trunk).
3. Written informed consent (and assent when applicable) obtained from subject or subject's legal representative
4. Ability for subject to comply with the requirements of the study.

Exclusion Criteria

1. History of inflammatory skin disease (e.g. psoriasis, atopic dermatitis, or bullous pemphigoid) that has been active in the past 10 years.
2. History of contact dermatitis to moisturizers.
3. History of chronic inflammatory conditions (such as cancer, arthritis, inflammatory bowel disease, or coronary artery disease). Participants with a history of localized skin cancer will not be excluded.
4. Current infection.
5. Open skin wounds.
6. Physical limitations or lack of a caregiver preventing application of a moisturizer to skin on the trunk and extremities.
7. Current use of topical medications, oral systemic immunomodulatory treatments, or anti-microbial treatments.
8. Diagnosis of primary or acquired immunodeficiency.
9. Use of skin moisturizer less than 1 week prior to enrollment visit, with the exception that participants may use non-study moisturizer/sunscreen on face, if used consistently throughout study period.
10. Inability to give informed consent.
11. Presence of a condition or abnormality that, in the opinion of the Investigator, would compromise the safety of the patient or the quality of the data.
12. If the participant does not meet all the above criteria, he/she will not be eligible for study participation.

Primary outcomes:
measure: Demonstrate feasibility
timeFrame: 8 weeks
Secondary outcomes:
measure: Change in composite inflammation score
timeFrame: 4 weeks
measure: Change in skin barrier function
timeFrame: 4 weeks
measure: Change in skin barrier function
timeFrame: 4 weeks
measure: Change in skin barrier function
timeFrame: 4 weeks
measure: Change in skin barrier function
timeFrame: 4 weeks
measure: Measures of skin microbial composition diversity
timeFrame: 4 weeks
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF
state: California
Study officials:
affiliation: University of California, San Francisco
name: Katrina Abuabara, MD
role: PRINCIPAL_INVESTIGATOR
References: