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Topical Rapamycin to Erase Angiofibromas in TSC (Treatment)

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ClinicalTrials.gov Identifier: NCT01526356
Recruitment Status : Completed
First Posted : February 3, 2012
Results First Posted : October 26, 2020
Last Update Posted : October 26, 2020
Sponsor:
Information provided by (Responsible Party):
Mary Kay Koenig, The University of Texas Health Science Center, Houston

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Angiofibromas
Tuberous Sclerosis
Interventions Drug: Placebo
Drug: Rapamycin
Enrollment 179
Recruitment Details  
Pre-assignment Details  
Arm/Group Title 1% Rapamycin 0.1 % Rapamycin Placebo
Hide Arm/Group Description

1% Rapamycin cream

Rapamycin: Study cream is applied nightly to the affected areas on the face. High Dose

0.1% Rapamycin cream

Rapamycin: Study cream is applied nightly to the affected areas on the face. Low Dose

Cream only

Placebo: Study cream is applied nightly to the affected areas on the face.

Period Title: Overall Study
Started 59 63 57
Completed 51 53 45
Not Completed 8 10 12
Arm/Group Title 1% Rapamycin 0.1 % Rapamycin Placebo Total
Hide Arm/Group Description

1% Rapamycin cream

Rapamycin: Study cream is applied nightly to the affected areas on the face. High Dose

0.1% Rapamycin cream

Rapamycin: Study cream is applied nightly to the affected areas on the face. Low Dose

Cream only

Placebo: Study cream is applied nightly to the affected areas on the face.

Total of all reporting groups
Overall Number of Baseline Participants 59 63 57 179
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 59 participants 63 participants 57 participants 179 participants
19.2  (13.0) 21.7  (12.4) 20.3  (14.3) 20.5  (13.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 59 participants 63 participants 57 participants 179 participants
Female
36
  61.0%
34
  54.0%
29
  50.9%
99
  55.3%
Male
23
  39.0%
29
  46.0%
28
  49.1%
80
  44.7%
1.Primary Outcome
Title Change From Baseline in the Facial Angiofibroma Grading Scale (AGS) Score
Hide Description Subject's lesion/s will be digitally photographed before initial application (visit 1), at each study visit (visits 2 through 6), and immediately prior to study termination (visit 7). Following completion of the study, all photographs will be evaluated by two independent dermatologists blinded to both the treatment arm and the stage of treatment. The dermatologists will assess each photograph's appearance using the facial Angiofibroma Grading Scale (AGS), which assesses the forehead, nose, cheeks, and chin for erythema, average lesion size, lesion density, and percent involvement, as well as presence of any pedunculated angiofibromas. A total score is reported with a range of 0 to 202, with higher scores representing a worse outcome.
Time Frame baseline, 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
This data was not collected for 12 in the 1% rapamycin arm, 17 in the 0.1% rapamycin arm, and 17 in the placebo arm.
Arm/Group Title 1% Rapamycin 0.1 % Rapamycin Placebo
Hide Arm/Group Description:

1% Rapamycin cream

Rapamycin: Study cream is applied nightly to the affected areas on the face. High Dose

0.1% Rapamycin cream

Rapamycin: Study cream is applied nightly to the affected areas on the face. Low Dose

Cream only

Placebo: Study cream is applied nightly to the affected areas on the face.

Overall Number of Participants Analyzed 47 46 40
Mean (Standard Deviation)
Unit of Measure: score on a scale
-13.89  (20.86) -12.71  (20.24) -1.39  (14.64)
2.Secondary Outcome
Title Photo Readers' Rating (Better, Same, or Worse) of Paired Baseline and End-of-trial (EOT) Photographs for Each Patient
Hide Description [Not Specified]
Time Frame baseline, 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
This data was not collected for 4 in the 1% rapamycin arm, 5 in the 0.1% rapamycin arm, and 6 in the placebo arm.
Arm/Group Title 1% Rapamycin 0.1 % Rapamycin Placebo
Hide Arm/Group Description:

1% Rapamycin cream

Rapamycin: Study cream is applied nightly to the affected areas on the face. High Dose

0.1% Rapamycin cream

Rapamycin: Study cream is applied nightly to the affected areas on the face. Low Dose

Cream only

Placebo: Study cream is applied nightly to the affected areas on the face.

Overall Number of Participants Analyzed 55 58 51
Measure Type: Count of Participants
Unit of Measure: Participants
better
45
  81.8%
38
  65.5%
13
  25.5%
same
5
   9.1%
11
  19.0%
15
  29.4%
worse
5
   9.1%
9
  15.5%
23
  45.1%
3.Secondary Outcome
Title Change in Quality of Life (QOL) Questionnaire Scores as Assessed by the Dermatology Life Quality Index (DLQI)
Hide Description The Dermatology life Quality Index (DLQI) is a ten-question questionnaire used to measure the impact of skin disease on the quality of life of an affected person. It is designed for people aged 16 years and above. Each question is scored from 0 to 3, giving a possible total score range from 0 (meaning no impact of skin disease on quality of life) to 30 (meaning maximum impact on quality of life).
Time Frame baseline, 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
This data was not collected for 29 in the 1% rapamycin arm, 34 in the 0.1% rapamycin arm, and 35 in the placebo arm.
Arm/Group Title 1% Rapamycin 0.1 % Rapamycin Placebo
Hide Arm/Group Description:

1% Rapamycin cream

Rapamycin: Study cream is applied nightly to the affected areas on the face. High Dose

0.1% Rapamycin cream

Rapamycin: Study cream is applied nightly to the affected areas on the face. Low Dose

Cream only

Placebo: Study cream is applied nightly to the affected areas on the face.

Overall Number of Participants Analyzed 30 29 22
Mean (Standard Deviation)
Unit of Measure: score on a scale
-1.5  (4.4) -3.2  (5.0) -1.6  (4.5)
4.Secondary Outcome
Title Change in Quality of Life (QOL) Questionnaire Scores as Assessed by the Children's Dermatology Life Quality Index (CDLQI)
Hide Description The Children's Dermatology life Quality Index (DLQI) is validated from the age of four years to 16 years. It is a ten-question questionnaire used to measure the impact of skin disease on the quality of life of an affected person. Each question is scored from 0 to 3, giving a possible total score range from 0 (meaning no impact of skin disease on quality of life) to 30 (meaning maximum impact on quality of life).
Time Frame baseline, 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
This data was not collected for 46 in the 1% rapamycin arm, 57 in the 0.1% rapamycin arm, and 48 in the placebo arm.
Arm/Group Title 1% Rapamycin 0.1 % Rapamycin Placebo
Hide Arm/Group Description:

1% Rapamycin cream

Rapamycin: Study cream is applied nightly to the affected areas on the face. High Dose

0.1% Rapamycin cream

Rapamycin: Study cream is applied nightly to the affected areas on the face. Low Dose

Cream only

Placebo: Study cream is applied nightly to the affected areas on the face.

Overall Number of Participants Analyzed 13 6 9
Mean (Standard Deviation)
Unit of Measure: score on a scale
-0.2  (4.1) -1.7  (3.1) -1.8  (2.6)
5.Secondary Outcome
Title Change in Quality of Life (QOL) Questionnaire Scores as Assessed by the Family Dermatology Life Quality Index (FDLQI)
Hide Description The Family Dermatology life Quality Index (FLQI) is designed for adult (more than 16 years of age) family members or partners of patients (of any age) with any skin disease. It is a ten-question questionnaire used to measure the impact of skin disease on the quality of life of an affected person. Each question is scored from 0 to 3, giving a possible total score range from 0 (meaning no impact of skin disease on quality of life) to 30 (meaning maximum impact on quality of life).
Time Frame baseline, 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
This data was not collected for 41 in the 1% rapamycin arm, 35 in the 0.1% rapamycin arm, and 38 in the placebo arm.
Arm/Group Title 1% Rapamycin 0.1 % Rapamycin Placebo
Hide Arm/Group Description:

1% Rapamycin cream

Rapamycin: Study cream is applied nightly to the affected areas on the face. High Dose

0.1% Rapamycin cream

Rapamycin: Study cream is applied nightly to the affected areas on the face. Low Dose

Cream only

Placebo: Study cream is applied nightly to the affected areas on the face.

Overall Number of Participants Analyzed 18 28 19
Mean (Standard Deviation)
Unit of Measure: score on a scale
-2.2  (3.2) -1.8  (5.2) 0.3  (3.4)
6.Other Pre-specified Outcome
Title Number of Events of Dermatologic Sensitivity at the Site of Application
Hide Description Dermatologic sensitivity includes pain, pruritis, or erythema at the application site.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo 0.1 % Rapamycin 1% Rapamycin
Hide Arm/Group Description:

Cream only

Placebo: Study cream is applied nightly to the affected areas on the face.

0.1% Rapamycin cream

Rapamycin: Study cream is applied nightly to the affected areas on the face. Low Dose

1% Rapamycin cream

Rapamycin: Study cream is applied nightly to the affected areas on the face. High Dose

Overall Number of Participants Analyzed 59 63 57
Measure Type: Number
Unit of Measure: number of events
Application site pain 6 2 1
Application site pruritis 5 0 1
Application site erythema 2 1 0
7.Other Pre-specified Outcome
Title Number of Participants With Systemic Uptake of Topically Applied Rapamycin
Hide Description Blood levels checked to confirm the lack of systemic rapamycin.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 1% Rapamycin 0.1 % Rapamycin Placebo
Hide Arm/Group Description:

1% Rapamycin cream

Rapamycin: Study cream is applied nightly to the affected areas on the face. High Dose

0.1% Rapamycin cream

Rapamycin: Study cream is applied nightly to the affected areas on the face. Low Dose

Cream only

Placebo: Study cream is applied nightly to the affected areas on the face.

Overall Number of Participants Analyzed 59 63 57
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
Time Frame 6 months
Adverse Event Reporting Description Serious adverse events were determined to be unrelated to study drug.
 
Arm/Group Title Placebo 0.1 % Rapamycin 1% Rapamycin
Hide Arm/Group Description

Cream only

Placebo: Study cream is applied nightly to the affected areas on the face.

0.1% Rapamycin cream

Rapamycin: Study cream is applied nightly to the affected areas on the face. Low Dose

1% Rapamycin cream

Rapamycin: Study cream is applied nightly to the affected areas on the face. High Dose

All-Cause Mortality
Placebo 0.1 % Rapamycin 1% Rapamycin
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/59 (0.00%)      0/63 (0.00%)      0/57 (0.00%)    
Hide Serious Adverse Events
Placebo 0.1 % Rapamycin 1% Rapamycin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/59 (1.69%)      1/63 (1.59%)      2/57 (3.51%)    
General disorders       
Chest pain  1  1/59 (1.69%)  1 0/63 (0.00%)  0 0/57 (0.00%)  0
Hepatobiliary disorders       
cholecystectomy  1  0/59 (0.00%)  0 0/63 (0.00%)  0 1/57 (1.75%)  1
Nervous system disorders       
Subependymal Giant Cell Astrocytoma (SEGA) resection  1  0/59 (0.00%)  0 1/63 (1.59%)  1 1/57 (1.75%)  1
1
Term from vocabulary, MedDRA
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1.1%
Placebo 0.1 % Rapamycin 1% Rapamycin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   10/59 (16.95%)      18/63 (28.57%)      22/57 (38.60%)    
Gastrointestinal disorders       
Nausea  1  0/59 (0.00%)  0 2/63 (3.17%)  2 0/57 (0.00%)  0
General disorders       
Mouth ulceration  1  1/59 (1.69%)  1 1/63 (1.59%)  1 0/57 (0.00%)  0
Infections and infestations       
Nasopharyngitis  1  0/59 (0.00%)  0 0/63 (0.00%)  0 2/57 (3.51%)  2
Nasal congestion  1  0/59 (0.00%)  0 0/63 (0.00%)  0 2/57 (3.51%)  2
Sinusitis  1  0/59 (0.00%)  0 1/63 (1.59%)  1 1/57 (1.75%)  1
Respiratory, thoracic and mediastinal disorders       
Cough  1  1/59 (1.69%)  1 1/63 (1.59%)  1 0/57 (0.00%)  0
Skin and subcutaneous tissue disorders       
Application site pain  1  1/59 (1.69%)  1 2/63 (3.17%)  2 6/57 (10.53%)  6
Application site pruritus  1  1/59 (1.69%)  1 0/63 (0.00%)  0 5/57 (8.77%)  5
Application site acne  1  1/59 (1.69%)  1 1/63 (1.59%)  1 3/57 (5.26%)  3
Cutaneous eruption  1  1/59 (1.69%)  1 2/63 (3.17%)  2 1/57 (1.75%)  1
Pruritus  1  2/59 (3.39%)  2 2/63 (3.17%)  2 0/57 (0.00%)  0
Application site erythema  1  0/59 (0.00%)  0 1/63 (1.59%)  1 2/57 (3.51%)  2
Sunburn  1  0/59 (0.00%)  0 1/63 (1.59%)  1 2/57 (3.51%)  2
Application site irritation  1  0/59 (0.00%)  0 2/63 (3.17%)  2 1/57 (1.75%)  1
Acne  1  1/59 (1.69%)  1 2/63 (3.17%)  2 0/57 (0.00%)  0
Application site papules  1  0/59 (0.00%)  0 1/63 (1.59%)  1 1/57 (1.75%)  1
Application site paraesthesia  1  1/59 (1.69%)  1 0/63 (0.00%)  0 1/57 (1.75%)  1
1
Term from vocabulary, MedDRA
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Mary Kay Koenig, MD
Organization: The University of Texas Health Science Center at Houston
Phone: 713-500-7142
EMail: mary.k.koenig@uth.tmc.edu
Layout table for additonal information
Responsible Party: Mary Kay Koenig, The University of Texas Health Science Center, Houston
ClinicalTrials.gov Identifier: NCT01526356    
Other Study ID Numbers: HSC-MS-11-0501
Department of Defense USAMRMC ( Other Grant/Funding Number: W81XWH-11-1-0240 )
First Submitted: February 1, 2012
First Posted: February 3, 2012
Results First Submitted: September 30, 2020
Results First Posted: October 26, 2020
Last Update Posted: October 26, 2020