Topical Rapamycin and Calcitriol for Angiofibroma of Tuberous Sclerosis
Primary Purpose
Facial Angiofibroma
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Rapamycin
Calcitriol
Rapamycin-calcitriol combination
Sponsored by
About this trial
This is an interventional treatment trial for Facial Angiofibroma focused on measuring Tuberous sclerosis complex, facial angiofibroma, rapamycin, calcitriol
Eligibility Criteria
Inclusion Criteria:
- Subjects must have been diagnosed or highly suspected as having TSC.
- Subjects must be aged 7 to 70 years at Screening, and can be either sex.
- Subjects must have symmetric facial angiofibromas.
Exclusion Criteria:
- Pregnancy or with a plan to be pregnant.
- Subjects who cannot comply the treatment protocol.
- Subjects with kidney or liver/ biliary dysfunction.
- Subjects with hypercalcaemia and patients known to suffer from abnormal calcium metabolism.
- Subjects on systemic treatment of calcium deficiency.
- Subjects known to be hypersensitive to rapamycin or calcitriol.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Rapamycin
Calcitriol
Rapamycin-calcitriol combination
Arm Description
Rapamycin(0.1%)
Calcitriol(3mcg/g)
Rapamycin(0.1%) with Calcitriol(3mcg/g)
Outcomes
Primary Outcome Measures
facial angiofibroma severity index (FASI)
the reduction of facial angiofibroma severity index (FASI) for the grade of erythema, papule size, elevation and extension of the lesions at week 12
Secondary Outcome Measures
Full Information
NCT ID
NCT03140449
First Posted
April 26, 2017
Last Updated
May 2, 2017
Sponsor
National Taiwan University Hospital
1. Study Identification
Unique Protocol Identification Number
NCT03140449
Brief Title
Topical Rapamycin and Calcitriol for Angiofibroma of Tuberous Sclerosis
Official Title
Study of Combination Therapy With Topical Rapamycin and Calcitriol for Cutaneous Lesions of Tuberous Sclerosis: A Double-blind Randomized Controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
September 2013
Overall Recruitment Status
Completed
Study Start Date
September 5, 2013 (Actual)
Primary Completion Date
November 7, 2016 (Actual)
Study Completion Date
April 25, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Taiwan University Hospital
4. Oversight
5. Study Description
Brief Summary
The aim of the study is to determine the effect and safety of topical rapamycin or calcitriol and their combination for the treatment of TSC-associated facial angiofibroma.
Methods: A total of 52 TSC patients including 20 male and 32 female subjects were recruited, and 50 of them completed the period 1 study. In period 1, topical rapamycin (0.1%) or calcitriol (3 mcg/g) single-agent therapy versus their combination were applied twice a day by a left-right randomized, split-face comparison for 12 weeks. The primary end point was the reduction of facial angiofibroma severity index (FASI) for the grade of erythema, papule size, elevation and extension of the lesions at week 12. In period 2, the patients entered an open-label study and were reassigned to use the more effective ointment on both cheeks for another 12 weeks (week 13-24). A follow-up FASI analysis for recurrence after drug discontinuance for 12 weeks was also performed (week 36). The secondary end point was the reduction of Visual Analysis Score (VAS) evaluated by the subjects themselves at week 12.
Detailed Description
Background: Tuberous sclerosis complex (TSC)-associated facial angiofibroma is psychologically debilitating to both patients and their family members. The pathogenesis of TSC stems from TSC1 or TSC2 mutations, leading to the defect in mechanistic target of rapamycin (mTOR) inhibition. Rapamycin is an mTOR inhibitor and is effective for TSC facial angiofibroma through topical administration. Calcitriol, a vitamin D3 analogue, has been shown to lessen skin fibrosis in scleroderma and may be therapeutically beneficial to angiofibromas.
Objectives: The aim of the study is to determine the effect and safety of topical rapamycin or calcitriol and their combination for the treatment of TSC-associated facial angiofibroma.
Methods: A total of 52 TSC patients including 20 male and 32 female subjects were recruited, and 50 of them completed the period 1 study. In period 1, topical rapamycin (0.1%) or calcitriol (3 mcg/g) single-agent therapy versus their combination were applied twice a day by a left-right randomized, split-face comparison for 12 weeks. The primary end point was the reduction of facial angiofibroma severity index (FASI) for the grade of erythema, papule size, elevation and extension of the lesions at week 12. In period 2, the patients entered an open-label study and were reassigned to use the more effective ointment on both cheeks for another 12 weeks (week 13-24). A follow-up FASI analysis for recurrence after drug discontinuance for 12 weeks was also performed (week 36). The secondary end point was the reduction of Visual Analysis Score (VAS) evaluated by the subjects themselves at week 12.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Facial Angiofibroma
Keywords
Tuberous sclerosis complex, facial angiofibroma, rapamycin, calcitriol
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
52 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Rapamycin
Arm Type
Experimental
Arm Description
Rapamycin(0.1%)
Arm Title
Calcitriol
Arm Type
Experimental
Arm Description
Calcitriol(3mcg/g)
Arm Title
Rapamycin-calcitriol combination
Arm Type
Experimental
Arm Description
Rapamycin(0.1%) with Calcitriol(3mcg/g)
Intervention Type
Drug
Intervention Name(s)
Rapamycin
Other Intervention Name(s)
Sirolimus
Intervention Description
topical rapamycin (0.1%) or calcitriol (3 mcg/g) single-agent therapy versus their combination were applied twice a day by a left-right randomized, split-face comparison for 12 weeks.
In period 2, the patients entered an open-label study and were reassigned to use the more effective ointment on both cheeks for another 12 weeks (week 13-24).
Intervention Type
Drug
Intervention Name(s)
Calcitriol
Other Intervention Name(s)
Rocaltrol
Intervention Description
topical rapamycin (0.1%) or calcitriol (3 mcg/g) single-agent therapy versus their combination were applied twice a day by a left-right randomized, split-face comparison for 12 weeks.
In period 2, the patients entered an open-label study and were reassigned to use the more effective ointment on both cheeks for another 12 weeks (week 13-24).
Intervention Type
Drug
Intervention Name(s)
Rapamycin-calcitriol combination
Other Intervention Name(s)
Sirolimus-Rocaltrol combination
Intervention Description
topical rapamycin (0.1%) or calcitriol (3 mcg/g) single-agent therapy versus their combination were applied twice a day by a left-right randomized, split-face comparison for 12 weeks.
In period 2, the patients entered an open-label study and were reassigned to use the more effective ointment on both cheeks for another 12 weeks (week 13-24).
Primary Outcome Measure Information:
Title
facial angiofibroma severity index (FASI)
Description
the reduction of facial angiofibroma severity index (FASI) for the grade of erythema, papule size, elevation and extension of the lesions at week 12
Time Frame
at week 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
7 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subjects must have been diagnosed or highly suspected as having TSC.
Subjects must be aged 7 to 70 years at Screening, and can be either sex.
Subjects must have symmetric facial angiofibromas.
Exclusion Criteria:
Pregnancy or with a plan to be pregnant.
Subjects who cannot comply the treatment protocol.
Subjects with kidney or liver/ biliary dysfunction.
Subjects with hypercalcaemia and patients known to suffer from abnormal calcium metabolism.
Subjects on systemic treatment of calcium deficiency.
Subjects known to be hypersensitive to rapamycin or calcitriol.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
YI-HUA LIAO, A.P.
Organizational Affiliation
A.P.
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Topical Rapamycin and Calcitriol for Angiofibroma of Tuberous Sclerosis
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