A Pilot of Pediatric/Adult Study of Gene Expression Profiling and Clinical Characterization of Phototoxicity

NCT00353158 | Completed Phase 1 FDA Drug

• 2 other identifiers: 06019806-AR-0198
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

This study will examine the phototoxicity, a reaction to light that is like exaggerated sunburn, which occurs in people who take medications such as voriconazole, a medication used to fight fungus. Sunscreens might protect the skin from the reaction. Although phototoxicity from voriconazole is not completely understood, it may be related to how that medication is metabolized in the liver by enzymes called cytochrome P450 enzymes-and mainly by one known as 2C19. A way to evaluate phototoxicity is through microarrays, which measure how much each gene is expressed in cells from tissues such as skin. Patients ages 8 and older who are scheduled to begin taking or who currently take voriconazole may be eligible for this study. Also, patients ages 18 to 45 in good health who have skin tone known as Type 2, which usually burns and tans only slightly following sun exposure, may be eligible. All patients will visit the Dermatology Clinic. They will complete two questionnaires, on medical history and medications, as well as the skin response to sunlight, and donate about 3 teaspoons of blood. Patients who are scheduled to take voriconazole will visit the clinic four times, that is, two visits 2 consecutive days before beginning the medication and two visits on 2 consecutive days after taking it for at least 7 days. Each visit will take 1 to 2 hours. Patients about to take voriconazole will have a blood test and undergo a physical exam of the skin test site, on the buttocks. Researchers will take photographs of the specific site and do tests to measure skin reaction to ultraviolet (UV) light. UV light will be shined on 15 small areas of the skin, each 1 x 1 centimeters. After 24 hours, any redness that occurs on the skin will be checked. Afterward, patients will begin taking voriconazole according to directions by the researchers. At 10 or more days later, patients will visit the clinic. Sunscreen will be applied and 1 hour later after administration of voriconazole, a blood sample will be drawn to check the level of medication. Then UV light will be shined on 23 areas of skin 1 x 1 centimeters. More photographs will be taken of test sites to record changes in skin redness. On the next day, the skin response will be evaluated. Participants in the control group will be asked to avoid UV radiation by wearing hats and clothing, and using sunscreen. They will be given the doxycycline, an antibiotic, and undergo procedures with UV light shined on small areas of the skin, on the buttocks. Control participants will have 7 study days, with visits lasting from 1 to 3 hours and probably not exceeding 8 hours. They will have two shave biopsies on Study Day 2 and on Study Day 7 to determine how the skin has responded to UV light exposures.

Conditions

Bacterial Infections; Healthy Volunteers; Fungal Infections

Keywords

Phototesting; UVR/UVA; Sunburn; Doxycycline; Voriconazole

Outcome Measures

Primary Outcomes (1)

• Global gene expression profiles

  fully evaluable microarray sets of doxycycline-associated phototoxic reactions

  After treatment with voriconazole/doxycycline

Study Arms (2)

A

ACTIVE COMPARATOR

Subjects currently on or previously on chronic voriconazole or subjects who are scheduled to begin voriconazole

Drug: Voriconazole

B

EXPERIMENTAL

100mg twice daily for 3 days. Two hours after the last dose of doxycycline is taken in the clinic, on-medication phototesting with ssUVR, UVA, and visible light will be performed.

Drug: Doxycycline

Interventions

Doxycycline DRUG

100mg twice daily for 3 days. Two hours after the last dose of doxycycline is taken in the clinic, on-medication phototesting with ssUVR, UVA, and visible light will be performed.

B

Voriconazole DRUG

After taking voriconazole for (Bullet)7 days to achieve a steady state of voriconazole for subjects, on-medication phototesting with ssUVR, UVA, and visible light will be performed.

A

Eligibility Criteria

• Age: 8 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects who are scheduled to begin voriconazole
• Subjects with any skin phototype who are scheduled to begin voriconazole therapy.
• Availability of unexposed skin for testing. Test sites for ssUVR, UVA, and visible light exposures should be devoid of sunburn, suntan, scars, active dermal lesions, prior radiotherapy exposure, and uneven skin tones. The presence of nevi will be acceptable if in the physician's judgment they will not interfere with the study results. (Excess hair is acceptable if clipped or shaved.)
• Ages \>= 8 years old.
• Ability to participate fully and comply with the procedures of the protocol in the opinion of the investigator.
• Ability of subjects or guardians to understand and sign the consent form. Children must give assent for participation in addition to parental consent.
• Subjects currently on or previously on chronic voriconazole
• Subjects with any skin phototype who have received or are currently receiving chronic voriconazole therapy.
• Ages \>= 8 years old.
• Ability to participate fully and comply with the procedures of the protocol in the opinion of the investigator.
• Ability of subjects or guardians to understand and sign the consent form. Children must give assent for participation in addition to parental consent.
• Healthy volunteers
• I) Screening visit arm.
• Healthy adults aged 18-45 year old of skin phototype II (age and skin phototype limits selected to simulate subjects evaluated in protocol 04-C-0120).
• No history of allergy to tetracyclines.

You may not qualify if:

• Subjects who are scheduled to begin voriconazole
• Extensive skin disease and no testable skin area available.
• History of allergic reactions to lidocaine for the adults who will undergo the modified shave biopsy.
• History of idiopathic abnormal response to sunlight, such as polymorphic light eruption or solar urticaria. Prior remote history of phototoxicity reaction allowed.
• Unable to comply with the requirements of the protocol.
• Any confounding past or present medical illness that in the judgment of the investigators would pose added risk for study participants (i.e. subjects with history of graft-versus-host disease; subjects on concurrent chemotherapy or completed chemotherapy within the preceding two weeks with known photoexacerbating agents such as alkylating agents, doxorubicin, methotrexate, or cisplatin; or subjects with previous radiotherapy to the intended sites for phototesting).
• Pregnancy.
• History of keloid formation in the adults who will undergo the modified shave biopsy.
• Subjects currently on or previously on chronic voriconazole
• Unable to comply with the requirements of the protocol.
• Any confounding past or present medical illness that in the judgment of the investigators would pose added risk for study participants.
• Healthy volunteers
• I) Screening visit arm.
• History of allergic reactions to lidocaine.
• Any confounding past or present medical illness that in the judgment of the investigators would pose added risk for study participants (i.e. subjects with history of graft-versus-host disease; subjects on concurrent chemotherapy with known photoexacerbating agents such as alkylating agents, doxorubicin, methotrexate, or cisplatin; or subjects with previous radiotherapy to the intended sites for phototesting).

Sponsors & Collaborators

• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Mycoses; Bacterial Infections; Sunburn

Interventions

Doxycycline; Voriconazole

Condition Hierarchy (Ancestors)

Bacterial Infections and Mycoses; Infections; Photosensitivity Disorders; Skin Diseases; Skin and Connective Tissue Diseases; Burns; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Heidi H Kong, M.D.

  National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2006
• First Posted: July 17, 2006
• Study Start: May 25, 2007
• Primary Completion: September 20, 2011
• Study Completion: September 20, 2011
• Last Updated: May 7, 2026

Record last verified: 2026-02-24

Locations

US (1)