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Protocol Details

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

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

06-AR-0198

Sponsoring Institute

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

Recruitment Detail

Type: Completed Study; data analyses ongoing
Gender: Male & Female
Min Age: 8
Max Age: 100

Referral Letter Required

No

Population Exclusion(s)

None

Keywords

Phototesting;
UVR/UVA;
Sunburn;
Doxycycline;
Voriconazole

Recruitment Keyword(s)

None

Condition(s)

Healthy Volunteers;
Fungal Infections;
Bacterial infections

Investigational Drug(s)

None

Investigational Device(s)

None

Intervention(s)

Drug: Doxycycline
Drug: Voriconazole

Supporting Site

National Institute of Arthritis and Musculoskeletal and Skin Diseases

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.

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Eligibility

INCLUSION CRITERIA:

Subjects who are scheduled to begin voriconazole

1. Subjects with any skin phototype who are scheduled to begin voriconazole therapy.

2. 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.)

3. Ages greater than or equal to 8 years old.

4. Ability to participate fully and comply with the procedures of the protocol in the opinion of the investigator.

5. Ability of subjects or guardians to understand and sign the consent form. Children must give assent for participation in addition to parental consent.

OR

Subjects currently on or previously on chronic voriconazole

1. Subjects with any skin phototype who have received or are currently receiving chronic voriconazole therapy.

2. Ages greater than or equal to 8 years old.

3. Ability to participate fully and comply with the procedures of the protocol in the opinion of the investigator.

4. Ability of subjects or guardians to understand and sign the consent form. Children must give assent for participation in addition to parental consent.

OR

Healthy volunteers

I) Screening visit arm.

1. Healthy adults aged 18-45 years old of skin phototype II (age and skin phototype limits selected to simulate subjects evaluated in protocol 04-C-0120).

2. No history of allergy to tetracyclines.

3. No systemic medications, herbal supplements or vitamins that are known to be associated with abnormal light response or effect on cytochrome P450 enzymes taken concurrently or within 7 days or 7 half-lives (whichever is longer) of phototesting.

4. No history of liver disease or hepatitis.

5. Willing to undergo screening dermatologic examination and bloodwork.

6. Ability to understand and sign the consent form.

II) Study visit arm

1. Anti-nuclear antibodies (ANA) less than 3 EU; Negative extractable nuclear antigen (ENA); and negative history of idiopathic abnormal response to sunlight, such as polymorphic light eruption or solar urticaria. Prior remote history of phototoxicity reactions acceptable.

2. 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.)

3. Liver function profile must be within limits of normal.

4. Ability to participate fully and comply with the procedures of the protocol in the opinion of the investigator.

EXCLUSION CRITERIA:

Subjects who are scheduled to begin voriconazole

1. Does not meet the inclusion criteria.

2. Extensive skin disease and no testable skin area available.

3. History of allergic reactions to lidocaine for the adults who will undergo the modified shave biopsy.

4. History of idiopathic abnormal response to sunlight, such as polymorphic light eruption or solar urticaria. Prior remote history of phototoxicity reaction allowed.

5. Unable to comply with the requirements of the protocol.

6. 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).

7. Pregnancy.

8. History of keloid formation in the adults who will undergo the modified shave biopsy.

OR

Subjects currently on or previously on chronic voriconazole

1. Does not meet the inclusion criteria.

2. Unable to comply with the requirements of the protocol.

3. Any confounding past or present medical illness that in the judgment of the investigators would pose added risk for study participants.

OR

Healthy volunteers

I) Screening visit arm.

1. Does not meet the Screening visit arm inclusion criteria.

2. History of allergic reactions to lidocaine.

3. 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).

4. Pregnancy.

5. History of keloid formation.

II) Study visit arm

1. Does not meet the Study visit arm inclusion criteria.

2. Extensive skin disease and no testable skin area available.

3. Anti-nuclear antibodies (ANA) greater than or equal to 3 EU or positive extractable nuclear antigen (ENA); prior history of idiopathic abnormal response to sunlight, such as polymorphic light eruption or solar urticaria. Prior remote history of phototoxicity reaction allowed.

4. Unable to comply with the requirements of the protocol.


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Citations:

Not Provided

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Contacts:

Principal Investigator

Referral Contact

For more information:

Heidi H. Kong, M.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
NIHBC 10 - CLINICAL CENTER BG RM 12N240D
10 CENTER DR
BETHESDA MD 20892
(301) 827-2460
konghe@mail.nih.gov

Heidi H. Kong, M.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
NIHBC 10 - CLINICAL CENTER BG RM 12N240D
10 CENTER DR
BETHESDA MD 20892
(301) 827-2460
konghe@mail.nih.gov

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office
1-888-NCI-1937
ncimo_referrals@mail.nih.gov

Clinical Trials Number:

NCT00353158

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