Efficacy Of Tocotrienol a Natural Vitamin E In Biopsy Wound (TOP/OTOP)

• ClinicalTrials.gov Identifier: NCT01579227
• Recruitment Status: Unknown
• First Posted: April 17, 2012
• Last Update Posted: January 29, 2018
• Sponsor: Chandan K Sen
• Collaborator: Carotech Inc.
• Information provided by (Responsible Party): Chandan K Sen, Ohio State University

Tracking Information

• First Submitted Date: April 13, 2012
• First Posted Date: April 17, 2012
• Last Update Posted Date: January 29, 2018
• Study Start Date: January 2012
• Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 21, 2014)

WOUND CLOSURE [ Time Frame: 1-2 month(s) ]

Wound closure will be assessed by results of conventional camera and thermal imaging in Group 1 and Group 2 subjects.

• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: January 21, 2014)

SCARRING [ Time Frame: 1-2 month (s) ]

Scarring will be assessed in group 1 and group 2 subjects by the Vancouver Scar Scale (VSS). Scoring will be performed by three blinded observers. The VSS evaluates vascularity (redness), height (hypertrophy), pliability (contracture and elastic texture) and pigmentation.

• Original Secondary Outcome Measures: Not Provided

Current Other Pre-specified Outcome Measures (submitted: August 21, 2014)

Wound closure and Increased Angiogenesis [ Time Frame: 1-2 months ]

Test whether miR-200b is silenced with tamoxifen resulting in increased angiogenesis and faster wound closure

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy Of Tocotrienol a Natural Vitamin E In Biopsy Wound
• Official Title: Efficacy Of Tocotrienol a Natural Vitamin E In Biopsy Wound.

Brief Summary

The following two objectives are proposed in healthy subjects to characterize (1) wound closure, (2) scar formation/appearance, and (3) inflammatory response:

Objective 1, (topical only - referred to as "TOP") - Topical application of Tocotrienol (TCT) vs placebo in bilateral punch biopsy

Objective 2, (oral and topical - referred to as "OTOP") - Combined oral supplementation and topical application of tocotrienol (TCT) vs placebo in bilateral punch biopsy

Objective 3, (topical only - referred to as "TAM") - Topical application of tamoxifen vs placebo in bilateral punch biopsy.

Objective 4, (topical only to normal skin) - Topical application of TCT vs placebo on bilateral lets on normal skin.

Detailed Description

• In nature, the vitamin E family is split into two classes: tocopherols (TCP) and tocotrienols (TCT). Members of the TCP and TCT family are biologically unique.

  • TCP are mainly found in green leafy vegetables while TCT are the primary vitamin E of seeds, including cereal grains such as wheat, rice, and barley.

• Vitamin E is thought to improve wound healing by inhibiting collagen synthesis and attenuating fibroblast proliferation and inflammation. However, outcomes based scientific literature on the therapeutic efficacy of vitamin E in skin wound closure is scant and has primarily focused on TCP.

  • Oral supplementation of TCP showed modest improvement in rodent wound closure, but the relevance of oral TCP supplementation in rats already receiving high dose vitamin E in a standard laboratory is questionable.
  • Topical TCP on surgical wounds of children have been shown to improve wound healing; yet no mechanistic basis for the observed effect was described.

• Preliminary observations from the PI's active IRB protocol to test TCT in scar appearance of surgical wounds led us to evaluate the potential of TCT vitamin E to improve wound closure in healthy subjects. To date, the therapeutic efficacy of TCT in either topical (TOP) or oral with topical (OTOP) applications for skin wound healing remains to be reported.

  • Preliminary observations also made show down-regulation of microRNA-200b supports cutaneous angiogenesis, the most important step in cutaneous wound healing. Tamoxifen silences mircroRNA-200b and later work has recognized that under non-neoplastic conditions, tamoxifen may induce angiogenesis.

• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples With DNA

Description:

Tissue biopsy will be collected twice in the study period.

• Sampling Method: Probability Sample
• Study Population: We plan to recruit 27 healthy adult subjects for the TOP group, 34 healthy adult subjects for the OTOP group,10 healthy adult subjects for the TAM group and 30 healthy subjects for Normal Skin.
• Condition: Scar

Intervention

• Device: Topical Tocotrienol (TCT)
  Natural Form Vitamin E topical cream(TCT)
  Other Name: TCT
• Dietary Supplement: Oral Tocotrienol Capsules (TCT)
  Natural Form Vitamin E Oral capsules (TCT)
  Other Name: TCT
• Device: Tamoxifen Cream
  Tamoxifen cream
• Device: Placebo cream
  Placebo cream
  Other Name: Placebo
• Dietary Supplement: placebo capsule
  placebo capsule
  Other Name: placebo

Study Groups/Cohorts

• 1-TOP group 1
  TOP group 1 will have biopsy #2 collected 3 days after 1st biopsy collected.
• TOP group 2
  TOP group 2 will have biopsy #2 collected 30 days after 1st biopsy collected.
• OTOP group-1
  OTOP will use topical cream (either topical tocotrienol (TCT) or placebo cream) as well as oral supplementation (either oral Tocotrienol capsules (TCT) or placebo capsules). OTOP group 1 will have biopsy #2 collected 3 days after 1st biopsy collected.
  Interventions:

  • Device: Topical Tocotrienol (TCT)
  • Dietary Supplement: Oral Tocotrienol Capsules (TCT)
  • Device: Placebo cream
  • Dietary Supplement: placebo capsule
• OTOP group-2
  OTOP will use topical cream (either topical tocotrienol (TCT) or placebo cream) as well as oral supplementation (either oral Tocotrienol capsules (TCT) or placebo capsules). OTOP group 2 will have biopsy #2 collected 30 days after 1st biopsy collected.
  Interventions:

  • Device: Topical Tocotrienol (TCT)
  • Dietary Supplement: Oral Tocotrienol Capsules (TCT)
  • Device: Placebo cream
  • Dietary Supplement: placebo capsule
• TAM Group 1
  TAM group 1 will have #2 biopsy collected 21 days after 1st biopsy collected. Tamoxifen cream and placebo cream will be applied where biopsies are collected from 1 week prior to having the biopsy procedure until the second biopsy is collected (21 days later).
  Intervention: Device: Tamoxifen Cream
• Normal Skin
  Placebo group will apply placebo and TCT cream that will be applied daily to a specified area on the subjects legs (normal skin) for 5 weeks. One leg will be applied with placebo and the other will be applied with TCT cream. Subjects will return weekly for 5 weeks, where non-invasive measurements using Laser Speckle imaging, will be completed at each study visit
  Interventions:

  • Device: Tamoxifen Cream
  • Device: Placebo cream

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: March 16, 2016): 101
• Original Estimated Enrollment (submitted: April 16, 2012): 71
• Estimated Study Completion Date: December 2018
• Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Ages- 18-50 (Both Male & Female)
• Non-smoker - having quit at least 3 months prior to enrollment
• Non-diabetic
• Non-pregnant or non-breastfeeding - verbal assent.
• If a female subject of childbearing age misses her menstrual period after the start of the study, she will inform the investigators and be given a pregnancy test to ensure, for safety reasons, that she is not pregnant. If she is pregnant, she will discontinue participation in the study.
• No current use of OTC medications or other form of supplements containing vitamin-E

Exclusion Criteria:

• Diabetes or HIV diagnosis
• Alcohol or drug abuse
• unable to provide informed consent
• Therapeutically anti-coagulated
• Prisoner
• Currently prescribed immunosuppressant medication

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 50 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01579227
• Other Study ID Numbers: 2011H0286
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Chandan K Sen, Ohio State University
• Study Sponsor: Chandan K Sen
• Collaborators: Carotech Inc.

Investigators

• Principal Investigator: Chandan K Sen, PhD; Ohio State University

• PRS Account: Ohio State University
• Verification Date: January 2017