Facial AngiofibromaPhase 3NCT03140449
Topical Rapamycin and Calcitriol for Angiofibroma of Tuberous Sclerosis
A Phase 3 study testing Rapamycin, Calcitriol and Rapamycin-calcitriol combination in people with Facial Angiofibroma, run by National Taiwan University Hospital.
Trial 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. Read more about this study
- Who is it for?
- Ages 7 to 65 years
- Conditions the study is for
- Facial Angiofibroma
- What is being tested?
- Rapamycin, Calcitriol and Rapamycin-calcitriol combination
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- No sites listed yet
- Study dates
- 5 Sep 2013to 25 Apr 2017
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 7 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
About this study
Official title: Study of Combination Therapy With Topical Rapamycin and Calcitriol for Cutaneous Lesions of Tuberous Sclerosis: A Double-blind Randomized Controlled Trial
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.
Read the 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.
- Conditions
- Facial Angiofibroma
- Being tested
- Rapamycin, Calcitriol, Rapamycin-calcitriol combination
- Keywords
- Tuberous sclerosis complex, facial angiofibroma, rapamycin, calcitriol
- Medical subject headings
- Tuberous Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RapamycinDrug
Also called Sirolimus
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).
CalcitriolDrug
Also called Rocaltrol
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).
Rapamycin-calcitriol combinationDrug
Also called Sirolimus-Rocaltrol 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).
| Study group | Role | What they receive |
|---|---|---|
| Rapamycin | Experimental | Rapamycin(0.1%) Receives: Drug: Rapamycin |
| Calcitriol | Experimental | Calcitriol(3mcg/g) Receives: Drug: Calcitriol |
| Rapamycin-calcitriol combination | Experimental | Rapamycin(0.1%) with Calcitriol(3mcg/g) Receives: Drug: Rapamycin-calcitriol combination |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: at week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2017
- Study start5 Sep 2013
- Primary completion7 Nov 2016
- Study completion25 Apr 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Facial AngiofibromaStudies of the same condition, open and under way.
- More trials run by National Taiwan University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- YI-HUA LIAO, A.P., Principal investigator, A.P.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03140449
- Sponsor's protocol ID
- 201306009MINB
- Status last verified
- Sep 2013
- First submitted
- 26 Apr 2017
- Last updated
- 4 May 2017
- Results posted
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of Combination Therapy With Topical Rapamycin and Calcitriol for Cutaneous Lesions of Tuberous Sclerosis: A Double-blind Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT03140449
- Acronym / sponsor ID
- 201306009MINB
- Conditions
- Facial Angiofibroma
- Keywords
- Tuberous sclerosis complex, facial angiofibroma, rapamycin, calcitriol
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Study start
- 5 Sep 2013 (actual)
- Primary completion
- 7 Nov 2016 (actual)
- Study completion
- 25 Apr 2017 (actual)
- First posted
- 4 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Rapamycin | Experimental | Drug: RapamycinRapamycin(0.1%) |
| Calcitriol | Experimental | Drug: CalcitriolCalcitriol(3mcg/g) |
| Rapamycin-calcitriol combination | Experimental | Drug: Rapamycin-calcitriol combinationRapamycin(0.1%) with Calcitriol(3mcg/g) |
Who may qualify
- Ages
- 7 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RapamycinAlso: Sirolimustopical 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). | Drug | Rapamycin |
| CalcitriolAlso: Rocaltroltopical 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). | Drug | Calcitriol |
| Rapamycin-calcitriol combinationAlso: Sirolimus-Rocaltrol combinationtopical 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). | Drug | Rapamycin-calcitriol combination |
Primary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2017.
- Individual participant dataSharing planned: Undecided
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
YI-HUA LIAO, A.P. principal investigator
A.P.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Rapamycin, Calcitriol and Rapamycin-calcitriol combination in people with Facial Angiofibroma, run by National Taiwan University Hospital.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 May 2017. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
facial angiofibroma severity index (FASI) (time frame: at week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 May 2017.