Cholesterol Cream vs Urea Cream for Skin Barrier and Quality of Life in Ichthyosis (CURE-ARCI)

A Comparative Study on the Efficacy of 10% Cholesterol Cream Versus 10% Urea Cream in Improving Skin Barrier Function and Quality of Life in Patients With Autosomal Recessive Congenital Ichthyosis

This study looks at whether a cream containing 10% cholesterol works better than a cream containing 10% urea for people with autosomal recessive congenital ichthyosis (ARCI), a rare inherited skin condition that causes dry, thickened, scaly skin from birth.

People with ARCI have a weakened skin barrier because their skin cannot properly produce or arrange the natural fats (lipids) needed to keep moisture in and irritants out. This leads to excessive water loss through the skin, dryness, itching, cracking, and a higher risk of skin infections. The current standard treatment is urea cream, which helps soften and remove scale but does not repair the underlying fat structure of the skin barrier. Cholesterol is one of the key natural fats that makes up a healthy skin barrier, so applying it directly to the skin may help rebuild that barrier more effectively than urea.

In this study, each participant will have one cream applied to one side of the body and the other cream applied to the matching area on the opposite side, so that each person acts as their own comparison. Researchers will measure how much water the skin loses (transepidermal water loss), skin hydration, and skin pH before and after treatment. They will also assess dryness and itching, take standardized clinical photographs, and ask participants to complete quality-of-life questionnaires (the Dermatology Life Quality Index, or its children's version, the Children's Dermatology Life Quality Index) as well as a satisfaction questionnaire for each cream.

The goal is to find out whether cholesterol cream restores the skin barrier better than urea cream, reduces dryness and itching more effectively, and leads to a better quality of life for people living with ARCI. The results may help guide more targeted skin care recommendations for this rare genetic condition.

This study is being conducted at the Institute of Dermatology, Bangkok, Thailand, and has been approved by the Institute's Ethics Committee.

Study Overview

• Status: Not yet recruiting
• Conditions: Autosomal Recessive Congenital Ichthyosis; Ichthyosis Inherited; Skin Barrier Dysfunction
• Intervention / Treatment: Drug: 10% Cholesterol Cream; Drug: 10% Urea cream

Detailed Description

Autosomal recessive congenital ichthyosis (ARCI) is a rare group of inherited skin disorders caused by mutations in genes required for normal lipid metabolism and barrier lipid assembly in the stratum corneum. The resulting epidermal barrier dysfunction produces generalized dryness, scaling, elevated transepidermal water loss (TEWL), chronic pruritus, and an increased susceptibility to skin infection. These manifestations begin at or shortly after birth and persist throughout life, with substantial negative effects on physical comfort, sleep, social functioning, and psychological well-being, particularly in children.

Current standard care relies on humectant and keratolytic agents such as 10% urea cream, which improve hydration and assist desquamation but do not address the underlying lipid deficiency responsible for barrier impairment. Cholesterol is a principal lipid component of the lamellar lipid matrix that cements corneocytes together within the stratum corneum. Exogenous application of cholesterol has been proposed as a mechanism-based intervention capable of correcting the disordered lipid lamellae characteristic of ARCI, thereby improving barrier integrity and reducing transepidermal water loss. Prior open-label, half-side comparison work in recessive X-linked ichthyosis demonstrated favorable clinical responses to topical cholesterol compared with urea, although that work did not include objective barrier measurements such as TEWL or validated quality-of-life instruments. Combination cholesterol-lovastatin preparations have also shown reductions in disease severity in ARCI. To date, no study has directly compared 10% cholesterol cream with 10% urea cream in patients with ARCI using both physiological barrier measurements and quality-of-life outcomes.

This investigation uses a prospective, randomized, split-body (intraindividual, half-side) comparison design, in which each participant serves as their own control: one cream is applied to a designated body area while the comparator cream is applied to the contralateral, matched area. This design was selected because ARCI is rare and clinically heterogeneous between individuals, making between-subject comparison less efficient than a within-subject comparison.

The primary objective is to compare the efficacy of 10% cholesterol cream and 10% urea cream in restoring skin barrier function, assessed by TEWL and skin hydration. Secondary objectives include comparison of clinical dryness and pruritus severity, changes in skin surface pH, assessment of quality of life using the Dermatology Life Quality Index (DLQI) or, for pediatric participants, the Children's Dermatology Life Quality Index (CDLQI), evaluation of participant satisfaction with each cream, and documentation of clinical change through standardized clinical photography.

Sample size was calculated using a two-dependent-means (paired t-test) formula based on an expected TEWL difference of 4 g/m²/h between treatments, a standard deviation of 6 g/m²/h, a two-sided significance level of 0.05, and 80% power, yielding a minimum requirement of 18 evaluable participants. To allow for an anticipated dropout or missing-data rate of 25%, the target enrollment was set at 24 participants.

This single-center study is being conducted at the Institute of Dermatology, Bangkok, Thailand, and has received approval from the Institute's Ethics Committee

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Chavalit Supsrisunjai, MD, PhD; Phone Number: +66825614441; Email: chervilius@gmail.com
• Study Contact Backup: Name: Aporn Bureethan, B.Sc.; Phone Number: +6622354803; Email: apornb@hotmail.com

Study Locations

• Thailand
  • Bangkok
    • Bangkok, Bangkok, Thailand, 10330
      • Institute of Dermatology
      • Contact: Aporn Bureethan, B.Sc.; Phone Number: +6695-207-2811; Email: apornb@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female patients aged 7 to 65 years
2. Confirmed diagnosis of Autosomal Recessive Congenital Ichthyosis (ARCI), established by history, family/genetic history, clinical presentation, and/or genetic testing
3. Disease activity stable (not in an acute flare)
4. Thai nationality
5. Receiving care at the Institute of Dermatology
6. Willing and able to provide informed consent (or, for participants under 18, assent with parental/legal guardian consent)

Exclusion Criteria:

1. Presence of any other concurrent skin disease
2. Known history of allergy to any component of the study creams
3. Active skin infection (e.g., herpes zoster, viral, fungal, bacterial, or parasitic infection)
4. History of any malignancy
5. Pregnant (confirmed by positive urine pregnancy test), breastfeeding, or planning pregnancy during the study period

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cholesterol Cream Side; The body area randomized to receive topical 10% cholesterol cream, applied twice daily to a designated skin site for the duration of the treatment period. This arm represents one side of the within-participant, split-body comparison, in which each participant simultaneously receives 10% cholesterol cream on one body area and 10% urea cream on the contralateral, anatomically matched area. Outcomes assessed on this side include transepidermal water loss (TEWL), skin hydration, skin surface pH, clinical dryness and pruritus severity, and standardized clinical photography.	Drug: 10% Cholesterol Cream; A topical cream formulated with 10% cholesterol, a physiological lipid component of the stratum corneum lamellar lipid matrix. Applied twice daily to a designated body area in patients with autosomal recessive congenital ichthyosis (ARCI), with the aim of restoring barrier lipid structure, reducing transepidermal water loss, and improving skin hydration, dryness, and pruritus compared with the contralateral side treated with 10% urea cream.
Active Comparator: Urea Cream Side; The contralateral, anatomically matched body area randomized to receive topical 10% urea cream, applied twice daily for the duration of the treatment period, serving as the active comparator. This arm represents the other side of the within-participant, split-body comparison, in which each participant simultaneously receives 10% urea cream on this body area and 10% cholesterol cream on the corresponding area on the opposite side. Outcomes assessed on this side include transepidermal water loss (TEWL), skin hydration, skin surface pH, clinical dryness and pruritus severity, and standardized clinical photography, allowing direct within-participant comparison against the cholesterol cream side.	Drug: 10% Urea cream; A topical cream formulated with 10% urea, a humectant and mild keratolytic agent representing the current standard-of-care emollient therapy for ichthyosis. Applied twice daily to the contralateral, anatomically matched body area in patients with ARCI, serving as the active comparator against 10% cholesterol cream within the same participant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Transepidermal Water Loss (TEWL)	TEWL measured using a Tewameter on the cholesterol cream-treated side versus the urea cream-treated side at each visit.	Baseline (Week 0), Week 1, Week 2, and Week 4
Change in Skin Hydration	Skin hydration measured using a Corneometer on each treated side at each visit.	Baseline (Week 0), Week 1, Week 2, and Week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Clinical Dryness and Pruritus Score	Clinical dryness and itch severity rated on a 0-4 scale (0 = none, 4 = very severe) by the same investigator at each visit, compared between treated sides.	Baseline (Week 0), Week 1, Week 2, and Week 4
Change in Investigator's Global Assessment (IGA) Score	Investigator-rated overall disease severity score assessed on each treated side at each visit.	Baseline (Week 0), Week 1, Week 2, and Week 4
Change in Skin Surface pH	Skin surface pH measured with a skin pH meter on each treated side at each visit.	Baseline (Week 0), Week 1, Week 2, and Week 4
Change in Dermatology Life Quality Index (DLQI) Score	The Dermatology Life Quality Index (DLQI) is a 10-item validated questionnaire assessing the impact of skin disease on quality of life in adult patients (aged 18 and above) over the preceding week. Each item is scored 0-3, giving a total score ranging from 0 (no impact on quality of life) to 30 (maximum impact on quality of life). Higher scores indicate a worse outcome. Scores are compared between Week 1, Week 2, and Week 4.	Week 1, Week 2, and Week 4 (not assessed at baseline)
Change in Children's Dermatology Life Quality Index (CDLQI) Score	The Children's Dermatology Life Quality Index (CDLQI) is a 10-item validated questionnaire assessing the impact of skin disease on quality of life in pediatric patients aged 7-17 years over the preceding week. Each item is scored 0-3, giving a total score ranging from 0 (no impact on quality of life) to 30 (maximum impact on quality of life). Higher scores indicate a worse outcome. Scores are compared between Week 1, Week 2, and Week 4.	Week 1, Week 2, and Week 4
Mean Satisfaction Score With 10% Cholesterol Cream and 10% Urea Cream Assessed by Likert Scale Questionnaire	Participant-reported satisfaction with each study cream (10% cholesterol cream and 10% urea cream) assessed separately at Week 4 using a study-specific Likert scale satisfaction questionnaire. Results are reported as mean and standard deviation (SD) for each cream and compared between the two products. Higher scores indicate greater satisfaction.	Week 4 only
Number of Participants With Clinical Improvement on Standardized Photography as Assessed by Blinded Investigator Review	Standardized digital clinical photographs of each treated side (cholesterol cream side versus urea cream side) are taken at each visit. Photographs are reviewed by a blinded investigator and compared against baseline images (Week 0) to assess clinical improvement in skin appearance. The number of participants showing clinical improvement on each treated side is reported at each time point.	Baseline (Week 0), Week 1, Week 2, and Week 4

Collaborators and Investigators

• Sponsor: Institute of Dermatology, Thailand

Study record dates

Study Major Dates

• Study Start (Estimated): July 15, 2026
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: June 30, 2026
• First Submitted That Met QC Criteria: July 7, 2026
• First Posted (Actual): July 8, 2026

Study Record Updates

• Last Update Posted (Actual): July 8, 2026
• Last Update Submitted That Met QC Criteria: July 7, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Urea Cream; Skin Barrier Function; Dermatology Life Quality Index; Autosomal Recessive Congenital Ichthyosis; Cholesterol Cream
• Other Study ID Numbers: IRB/IEC No. 021/2568

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