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Topical Rapamycin and Calcitriol for Angiofibroma of Tuberous Sclerosis

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ClinicalTrials.gov Identifier: NCT03140449
Recruitment Status : Completed
First Posted : May 4, 2017
Last Update Posted : May 4, 2017
Sponsor:
Information provided by (Responsible Party):
National Taiwan University Hospital

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.


Condition or disease Intervention/treatment Phase
Facial Angiofibroma Drug: Rapamycin Drug: Calcitriol Drug: Rapamycin-calcitriol combination Phase 3

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 52 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Study of Combination Therapy With Topical Rapamycin and Calcitriol for Cutaneous Lesions of Tuberous Sclerosis: A Double-blind Randomized Controlled Trial
Actual Study Start Date : September 5, 2013
Actual Primary Completion Date : November 7, 2016
Actual Study Completion Date : April 25, 2017


Arm Intervention/treatment
Experimental: Rapamycin
Rapamycin(0.1%)
Drug: Rapamycin

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 Name: Sirolimus

Experimental: Calcitriol
Calcitriol(3mcg/g)
Drug: Calcitriol

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 Name: Rocaltrol

Experimental: Rapamycin-calcitriol combination
Rapamycin(0.1%) with Calcitriol(3mcg/g)
Drug: Rapamycin-calcitriol combination

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 Name: Sirolimus-Rocaltrol combination




Primary Outcome Measures :
  1. facial angiofibroma severity index (FASI) [ Time Frame: at week 12 ]
    the reduction of facial angiofibroma severity index (FASI) for the grade of erythema, papule size, elevation and extension of the lesions at week 12



Information from the National Library of Medicine

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Ages Eligible for Study:   7 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subjects must have been diagnosed or highly suspected as having TSC.
  2. Subjects must be aged 7 to 70 years at Screening, and can be either sex.
  3. Subjects must have symmetric facial angiofibromas.

Exclusion Criteria:

  1. Pregnancy or with a plan to be pregnant.
  2. Subjects who cannot comply the treatment protocol.
  3. Subjects with kidney or liver/ biliary dysfunction.
  4. Subjects with hypercalcaemia and patients known to suffer from abnormal calcium metabolism.
  5. Subjects on systemic treatment of calcium deficiency.
  6. Subjects known to be hypersensitive to rapamycin or calcitriol.

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 ClinicalTrials.gov identifier (NCT number): NCT03140449


Sponsors and Collaborators
National Taiwan University Hospital
Investigators
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Principal Investigator: YI-HUA LIAO, A.P. A.P.

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Responsible Party: National Taiwan University Hospital
ClinicalTrials.gov Identifier: NCT03140449     History of Changes
Other Study ID Numbers: 201306009MINB
First Posted: May 4, 2017    Key Record Dates
Last Update Posted: May 4, 2017
Last Verified: September 2013
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by National Taiwan University Hospital:
Tuberous sclerosis complex
facial angiofibroma
rapamycin
calcitriol

Additional relevant MeSH terms:
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Calcitriol
Sclerosis
Tuberous Sclerosis
Angiofibroma
Pathologic Processes
Hamartoma
Neoplasms
Neoplasms, Multiple Primary
Neoplastic Syndromes, Hereditary
Malformations of Cortical Development, Group I
Malformations of Cortical Development
Nervous System Malformations
Nervous System Diseases
Neurocutaneous Syndromes
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Congenital Abnormalities
Genetic Diseases, Inborn
Neoplasms, Vascular Tissue
Neoplasms by Histologic Type
Sirolimus
Everolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs