Topical Rapamycin and Calcitriol for Angiofibroma of Tuberous Sclerosis
Condition: Facial Angiofibroma
MeSH terms: Tuberous Sclerosis; Angiofibroma; Sclerosis
Study type: Interventional
Phase: Phase 3

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.
    

Intervention name(s): Rapamycin; Calcitriol; Rapamycin-calcitriol combination
Intervention type(s): Drug; Drug; Drug
Intervention description(s): 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).; 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).; 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).
Other intervention name(s): Sirolimus; Rocaltrol; Sirolimus-Rocaltrol combination
Intervention MeSH terms: Calcitriol; Sirolimus; Temsirolimus; MTOR Inhibitors
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Tuberous sclerosis complex; facial angiofibroma; rapamycin; calcitriol