Phase 1 Study of the Effects of Combining Topical FDA-approved Drugs on Age-related Pathways on the Skin of Healthy Volunteers

NCT ID: NCT03072485

Last Updated: 2019-04-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-01
• Study Completion Date: 2019-02-22

Brief Summary

This is a phase 1 study in healthy adult volunteers to examine the effects of 3 FDA approved medications on skin aging when applied in topical form. This is an open label, placebo controlled study.

Detailed Description

The primary endpoint of the study is the profile of differences in transcript levels of age-associated genes such as those in the lamin-A, insulin like growth factor (IGF) and NFKB pathways as well as noncoding RNAs in topical agent-exposed arm skin versus placebo exposed arm skin in healthy volunteers. The secondary endpoints include (1) differences in skin wrinkling using a 4 point Likert scale for wrinkle severity between placebo and topical agent exposed arm skin after 4 weeks of usage; (2) the type and severity of adverse events, both systemic and skin localized after exposure to both topical agent and placebo vehicle cream.

Conditions

Aging

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Sirolimus, metformin, diclofenac

First five enrolled participants

Group Type: OTHER

Sirolimus

Intervention Type: DRUG

Topical sirolimus applied to the skin

Metformin

Intervention Type: DRUG

Topical metformin applied to the skin

Diclofenac

Intervention Type: DRUG

Topical diclofenac applied to the skin

Metformin, diclofenac

Sixth to tenth enrolled participants

Group Type: OTHER

Metformin

Intervention Type: DRUG

Topical metformin applied to the skin

Diclofenac

Intervention Type: DRUG

Topical diclofenac applied to the skin

Interventions

Sirolimus

Topical sirolimus applied to the skin

Intervention Type: DRUG

Metformin

Topical metformin applied to the skin

Intervention Type: DRUG

Diclofenac

Topical diclofenac applied to the skin

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Age greater than or equal to 55 years

2. Female

3. All 4 grandparents of European descent

4. Fitzpatrick Skin type 1-3 (fair skin type)

5. Presence of moderate to severe fine wrinkling on arm skin

6. Presence of moderate to severe dyspigmentation on arm skin

7. Normal or overweight body mass index

Exclusion Criteria

1. History of laser treatment or chemical peels to to arm

2. History of topical anti-aging products (includes retinol, tretinoin, tazarotene, azelaic acid, hydroquinone) to skin within 6 weeks of starting study

3. History of surgical procedures to arm skin area including removal of benign or malignant skin cancers in the area of topical study agent application

4. Current skin conditions in the area of arms including seborrheic keratosis, rosacea, eczema that may obscure study assessment

5. History of abnormal scarring

6. Uncontrolled medical problems including concurrent infection or malignancy at time of enrollment

7. Unable to provide and sign written informed consent

8. Unable to comply with study-related procedures including keeping study diary, application of topical study agents, avoidance of direct sun exposure >5 minutes per day or ultraviolet tanning bed usage

9. Not willing to provide two small skin biopsies at end of study

10. Known allergy to sirolimus, diclofenac or metformin.

11. Known immunosuppression including organ transplant, HIV, autoimmune disease, and chronic leukemia or lymphoma

12. Fasting blood sugar above the upper limit of normal for Stanford laboratory

13. Diarrhea

14. Use of greater than one alcoholic beverage per day

15. Stress such as surgery or trauma within 2 weeks of enrollment

16. Liver disease such as hepatitis B or C

17. Planning to embark on dieting, caloric restriction or new exercise regimen during the study to lose weight.

18. Unable to refrain from using any topical agent on arms besides the study agents provided for duration of study.

19. Hematocrit, hemoglobin, platelets, white blood cell count, serum Na, K, Cr, aspartate aminotransferase (AST), alanine aminotransferase (ALT) greater or lesser than 1.5 times limits of normal.

20. History of heart failure, coronary artery disease, including angina, coronary artery bypass graft, pacemaker or stent placement

21. History of bleeding or ulcers of the gastrointestinal tract

22. History of diabetes mellitus

23. Current use of blood thinners (includes heparin, warfarin and aspirin)

24. Current use of strong cytochrome P 450 (CYP) 3A4 inhibitor and/or P-gp (examples include ketoconazole, voriconazole, itraconazole, erythromycin, clarithromycin) or strong inducers of CYP3A4 and/or P-gp (examples include rifampin or rifabutin)

25. Abnormal lipid panel as defined by upper limit of normal at Stanford laboratory

• Minimum Eligible Age: 55 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Anne Chang

OTHER

Sponsor Role: lead

Responsible Party

Anne Chang

Associate Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Anne Chang, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Stanford Dermatology

Redwood City, California, United States

Countries

United States

Other Identifiers

IRB-37203

Identifier Type: -

Identifier Source: org_study_id