Vitamin D Levels in the Skin of Healthy Subjects After Oral Supplementation

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01447355
First received: October 4, 2011
Last updated: September 27, 2013
Last verified: September 2013
  Purpose

This pilot phase I trial studies vitamin D levels in the skin of healthy subjects after oral supplementation. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of cholecalciferol, a vitamin D, may keep skin cancer from forming.


Condition Intervention Phase
Healthy, no Evidence of Disease
Skin Cancer
Drug: cholecalciferol
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Pilot Study on the Bioactivity of Vitamin D in the Skin After Oral Supplementation

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Changes in VDR expression from baseline to post-intervention [ Time Frame: From baseline to post-intervention ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Modulation in CYP24 expression in keratinocytes in photoprotected and photodamaged areas [ Time Frame: Up to 9 weeks ] [ Designated as safety issue: No ]
  • Modulation of VDR in keratinocytes in photodamaged skin [ Time Frame: Up to 9 weeks ] [ Designated as safety issue: No ]
  • Changes in a panel of biomarkers of skin differentiation including caspase 14, loricrin, and stratum corneum thickness in keratinocytes in photo-protected and damaged skin [ Time Frame: From baseline to 9 weeks ] [ Designated as safety issue: No ]
  • Changes in 25-hydroxyvitamin D serum levels [ Time Frame: From baseline to 9 weeks ] [ Designated as safety issue: No ]
  • Changes in calcium, phosphate, and PTH [ Time Frame: From baseline to 9 weeks ] [ Designated as safety issue: No ]

Enrollment: 25
Study Start Date: August 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Prevention (cholecalciferol)
Participants receive cholecalciferol PO twice weekly for up to 8-9 weeks.
Drug: cholecalciferol
Given PO
Other Names:
  • Calciol
  • Vitamin D3

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine if high-dose oral cholecalciferol supplementation increases vitamin D receptor (VDR) expression in keratinocytes from photoprotected areas in healthy subjects with documented insufficient serum levels of 25-hydroxyvitamin D (defined as =< 30.0 ng/mL).

SECONDARY OBJECTIVES:

I. To assess the modulation in CYP24 expression in keratinocytes (from photoprotected and photodamaged skin samples).

II. To assess the modulation in VDR expression in keratinocytes (from photodamaged skin samples).

III. To assess the mechanistic information concerning the action of cholecalciferol supplementation in the state of keratinocytic differentiation by assessing caspase 14, loricrin, and assessment of stratum corneum thickness.

IV. To assess the safety and tolerability of high-dose cholecalciferol supplementation in this patient cohort, including the evaluation of calcium, phosphate, and parathyroid hormone (PTH).

V. To assess the 25-hydroxyvitamin D levels after intervention supplementation.

TERTIARY OBJECTIVES:

I. To assess the corresponding VDR and CYP24 expression in benign melanocytic nevi. (Exploratory)

OUTLINE:

Participants receive cholecalciferol orally (PO) twice weekly for up to 8-9 weeks.

After completion of study treatment, participants are followed up for 10-14 days.

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Documented insufficient serum levels of 25-hydroxyvitamin D =< 30.0 ng/mL
  • At least moderate sun-damaged skin on the mid-upper right dorsal forearm
  • Karnofsky performance status of at least 80%
  • Leukocytes âÃÂ¥ 3,000/ÃüL
  • Absolute neutrophil count âÃÂ¥ 1,500/ÃüL
  • Platelets âÃÂ¥ 100,000/ÃüL
  • Total bilirubin âä 2.0 mg/dL
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< institutional upper limit of normal (ULN)
  • Creatinine âä 1.4 mg/dL
  • Serum calcium 8.4-10.6 mg/dL
  • Parathyroid hormone (PTH): male 8.3-10.4 mg/dL; female 8.4-10.6 mg/dL
  • Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence; surgical sterilization; or at least one year post-menopausal) prior to study entry and for the duration of study participation
  • Skin phototype II or III as defined according to their skin response to sunlight:

    • Skin phototype II will always burn, and tan minimally after 45-60 min of unprotected exposure to the summer sun between 12-1pm
    • Skin phototype III will sometimes burn, and almost always tan after 45-60 min of unprotected exposure to the summer sun between 12-1pm
  • Ability to understand and willingness to sign written informed consent
  • Participants may not have acute or chronic hypervitaminosis D or hypercalcemia
  • No history of increased arterial calcification or atherosclerosis, sarcoidosis, histoplasmosis, hyperparathyroidism, lymphoma, or kidney disease
  • No current use of digoxin (Lanoxin, digitalis), cholestyramine (Prevalite, Questran), colestipol (Cholestid), oral steroids (prednisone and others), and antacids that contain magnesium
  • Participants may not be receiving any other investigational agents; if they have completed a clinical-intervention trial recently, there must be a 30-day period between completing the previous study and entering this study
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to cholecalciferol, lidocaine, or xylocaine
  • No uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant and breastfeeding women are excluded from this study
  • No invasive cancer or cancer treatment within the past five years, except non-melanoma skin cancer
  • No immunosuppression by virtue of medication or disease; this includes acquired immune deficiency syndrome (AIDS) patients, subjects taking oral prednisone, and subjects on immunosuppressants/immunomodulators (cyclosporine, chemotherapeutic agents, or biologic therapy), as determined by the examining investigator/co-investigator
  • Unwilling or unable to refrain from taking herbal medicines or above-standard vitamin or mineral during the study

    • A standard daily multivitamin/mineral supplement is acceptable if it contains ÃâÃä 600 IU of vitamin D, or ÃâÃä the recommended dietary allowance (RDA) of calcium, and the subject has been taking a stable dose for at least 30 days
    • Potential subjects who are taking above-standard doses of supplements may be re-considered for participation after a 30-day wash-out period
  • No participants who have used tanning beds or other methods to promote sun-tanning within 6 months of study entry; such practices may not be undertaken during participation in the study
  • Participants unwilling to minimize their exposure to sunlight by applying sunscreen/sunblock or by wearing clothing to shield their skin, during outdoor activities, while they are enrolled in the study
  • Individuals receiving concurrent topical therapy with retinoids, steroids, 5-fluorouracil, Levulan, Vaniqa (eflornithine), Solaraze, or Imiquimod (AldaraÃÃî) within 30 days prior to study enrollment will be excluded; subjects may be reconsidered for eligibility 30 days after the last treatment
  • Individuals who have had treatment for basal cell carcinoma or squamous cell carcinoma on the skin of the right forearm within six months prior to evaluation for the study will not be eligible; these subjects will be encouraged to return for re-evaluation once the six-month period is over
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01447355

Locations
United States, Arizona
University of Arizona Health Sciences Center
Tucson, Arizona, United States, 85724
Sponsors and Collaborators
Investigators
Principal Investigator: Clara Curiel-Lewandrowski University of Arizona Health Sciences Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01447355     History of Changes
Other Study ID Numbers: NCI-2011-03469, NCI-2011-03469, CDR0000712963, 11-0270-04, UAZ10-16-03, N01CN35158
Study First Received: October 4, 2011
Last Updated: September 27, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Skin Neoplasms
Neoplasms by Site
Neoplasms
Skin Diseases
Cholecalciferol
Vitamin D
Ergocalciferols
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Bone Density Conservation Agents

ClinicalTrials.gov processed this record on July 22, 2014