Topical Rapamycin to Erase Angiofibromas in TSC (Treatment)

• 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: The University of Texas Health Science Center, Houston
• Information provided by (Responsible Party): Mary Kay Koenig, The University of Texas Health Science Center, Houston

Study Description

Brief Summary:

The study is a multi-center prospective, randomized, double-blind, placebo-controlled evaluation of the safety and efficacy of a topically applied formulation of rapamycin to cutaneous angiofibromas in subjects with Tuberous Sclerosis Complex (TSC). Subjects will apply either the topical vehicle containing rapamycin or the topical vehicle alone nightly to their angiofibromas for six months.

The primary goal of this study is to evaluate the efficacy of the topical medication for reduction of cutaneous angiofibromas in patients with TSC. The secondary goal of this study is to confirm the safety of the topical medication.

Condition or disease	Intervention/treatment	Phase
Angiofibromas; Tuberous Sclerosis	Drug: Placebo; Drug: Rapamycin	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 179 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Topical Rapamycin to Erase Angiofibromas in TSC-Multicenter Evaluation of a Novel Therapy
• Study Start Date: May 2012
• Actual Primary Completion Date: August 2014
• Actual Study Completion Date: August 2014

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo; Cream only	Drug: Placebo; Study cream is applied nightly to the affected areas on the face.; Other Name: Rapamycin
Active Comparator: 0.1 % Rapamycin; 0.1% Rapamycin cream	Drug: Rapamycin; Study cream is applied nightly to the affected areas on the face. Low Dose
Active Comparator: 1% Rapamycin; 1% Rapamycin cream	Drug: Rapamycin; Study cream is applied nightly to the affected areas on the face. High Dose

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in the Facial Angiofibroma Grading Scale (AGS) Score [ Time Frame: baseline, 6 months ]
   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.

Secondary Outcome Measures :

1. Photo Readers' Rating (Better, Same, or Worse) of Paired Baseline and End-of-trial (EOT) Photographs for Each Patient [ Time Frame: baseline, 6 months ]
2. Change in Quality of Life (QOL) Questionnaire Scores as Assessed by the Dermatology Life Quality Index (DLQI) [ Time Frame: baseline, 6 months ]
   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).
3. Change in Quality of Life (QOL) Questionnaire Scores as Assessed by the Children's Dermatology Life Quality Index (CDLQI) [ Time Frame: baseline, 6 months ]
   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).
4. Change in Quality of Life (QOL) Questionnaire Scores as Assessed by the Family Dermatology Life Quality Index (FDLQI) [ Time Frame: baseline, 6 months ]
   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).

Other Outcome Measures:

1. Number of Events of Dermatologic Sensitivity at the Site of Application [ Time Frame: 6 months ]
   Dermatologic sensitivity includes pain, pruritis, or erythema at the application site.
2. Number of Participants With Systemic Uptake of Topically Applied Rapamycin [ Time Frame: 6 months ]
   Blood levels checked to confirm the lack of systemic rapamycin.

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Subjects must be willing and able to comply with all trial requirements.
• Subject has a diagnosis of TSC and has visible facial angiofibromas.
• Female subjects of child bearing potential must not be pregnant and must agree to use appropriate contraceptive methods .

Exclusion Criteria:

• Subject is currently receiving therapy with Rapamycin.
• Subject is receiving any form of immunosuppression or has previously experienced immune dysfunction.
• Subject is currently participating in or has participated within the last 30 days in a clinical trial involving an investigational drug.
• Subject has a known hypersensitivity to either the vehicle or Rapamycin.
• Subject is a pregnant or nursing female.
• Subject has other dermatologic conditions that would preclude or prevent adequate assessment of changes to their facial angiofibromas.
• Subject has had laser surgery, cryotherapy, or other dermatologic treatment to their facial angiofibromas within the previous 6 months.

Contacts and Locations

Locations

United States, Alabama

University of Alabama at Birmingham

Birmingham, Alabama, United States, 35294

United States, California

UCLA Mattel Children's Hospital

Los Angeles, California, United States, 90095

Jack & Julia Center for TSC at Oakland Children's Hospital & Research Center

Oakland, California, United States, 94609

United States, Maryland

Kennedy Krieger Institute

Baltimore, Maryland, United States, 21205

United States, Massachusetts

Herscot Center for Adults and Children with TSC Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

United States, Minnesota

Clinic Without Walls

Saint Paul, Minnesota, United States, 55102-2697

United States, Ohio

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States, 45229

United States, Texas

Texas Scottish Rite Hospital

Dallas, Texas, United States, 75219

The University of Texas Medical School at Houston

Houston, Texas, United States, 77030

Australia, New South Wales

Sydney Children's Hospital

Sydney, New South Wales, Australia

Sponsors and Collaborators

The University of Texas Health Science Center, Houston

Investigators

• Principal Investigator: Mary Kay Koenig, MD; The University of Texas Medical School at Houston
• Principal Investigator: Hope Northrup, MD; The University of Texas Medical School at Houston

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Koenig MK, Bell CS, Hebert AA, Roberson J, Samuels JA, Slopis JM, Tate P, Northrup H; TREATMENT Trial Collaborators. Efficacy and Safety of Topical Rapamycin in Patients With Facial Angiofibromas Secondary to Tuberous Sclerosis Complex: The TREATMENT Randomized Clinical Trial. JAMA Dermatol. 2018 Jul 1;154(7):773-780. doi: 10.1001/jamadermatol.2018.0464.

• Responsible Party: Mary Kay Koenig, Associate Professor, 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 Posted: February 3, 2012
• Results First Posted: October 26, 2020
• Last Update Posted: October 26, 2020
• Last Verified: September 2020

Keywords provided by Mary Kay Koenig, The University of Texas Health Science Center, Houston:

Angiofibroma; Tuberous Sclerosis; Rapamycin; Sirolimus; mTOR

Additional relevant MeSH terms:

Tuberous Sclerosis; Angiofibroma; Sclerosis; 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; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antineoplastic; Antineoplastic Agents; Antifungal Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs