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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03072485
Recruitment Status : Completed
First Posted : March 7, 2017
Last Update Posted : April 1, 2019
Information provided by (Responsible Party):
Anne Chang, Stanford University

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.

Condition or disease Intervention/treatment Phase
Aging Drug: Sirolimus Drug: Metformin Drug: Diclofenac Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Phase 1 Study of the Effects of Combining Topical FDA-approved Drugs on Age-related Pathways on the Skin of Healthy Volunteers
Actual Study Start Date : March 1, 2017
Actual Primary Completion Date : February 22, 2019
Actual Study Completion Date : February 22, 2019

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Sirolimus, metformin, diclofenac
First five enrolled participants
Drug: Sirolimus
Topical sirolimus applied to the skin

Drug: Metformin
Topical metformin applied to the skin

Drug: Diclofenac
Topical diclofenac applied to the skin

Metformin, diclofenac
Sixth to tenth enrolled participants
Drug: Metformin
Topical metformin applied to the skin

Drug: Diclofenac
Topical diclofenac applied to the skin

Primary Outcome Measures :
  1. Profile of gene transcript changes [ Time Frame: 4 weeks ]
    Profile of gene transcript changes

Secondary Outcome Measures :
  1. Wrinkle score [ Time Frame: 4 weeks ]
    on Likert scale

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   55 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03072485

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United States, California
Stanford Dermatology
Redwood City, California, United States, 94603
Sponsors and Collaborators
Anne Chang
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Principal Investigator: Anne Chang, MD Stanford University

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Responsible Party: Anne Chang, Associate Professor, Stanford University Identifier: NCT03072485    
Other Study ID Numbers: IRB-37203
First Posted: March 7, 2017    Key Record Dates
Last Update Posted: April 1, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Anne Chang, Stanford University:
Additional relevant MeSH terms:
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Hypoglycemic Agents
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action