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

Aging Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03072485
• Other study ID #: IRB-37203
• Status: Completed
• Phase: Phase 1
• Start date: March 1, 2017
• Est. completion date: February 22, 2019

Study information

• Verified date: March 2019
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: February 22, 2019
• Est. primary completion date: February 22, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 55 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Aging

Intervention

Drug:
• Sirolimus
Topical sirolimus applied to the skin
• Metformin
Topical metformin applied to the skin
• Diclofenac
Topical diclofenac applied to the skin

Locations

Country	Name	City	State
United States	Stanford Dermatology	Redwood City	California

Sponsors (1)

Lead Sponsor	Collaborator
Anne Chang

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Profile of gene transcript changes	Profile of gene transcript changes	4 weeks
Secondary	Wrinkle score	on Likert scale	4 weeks