Randomized Pilot Study for the Treatment of Cutaneous Leiomyomas With Botulinum Toxin
Cutaneous leiomyomas are benign tumors of smooth muscle origin. They can be very painful, and current treatments for the tumors and for the associated pain do not produce satisfactory results. One potential treatment for localized severe muscle pain involves injections with botulinum toxin A. This study will investigate the effectiveness, side effects, and dosage of botulinum toxin A (BOTOX) as a treatment for patients with pain associated with cutaneous leiomyomas.
This study will include 18 subjects, all of whom will be 18 years of age and older, who have pain associated with cutaneous leiomyomas.
For the 24-week study, patients will be randomly assigned to one of two treatment groups. Neither the study team nor the patient will know to which group patients have been assigned. Before the study begins, all participants must provide a full medical history for research and evaluation purposes, fill out pain and quality-of-life questionnaires, and undergo an ice test in which researchers will apply ice to the site of the cutaneous leiomyomas and ask participants to evaluate the level of pain before and after ice application. Both groups will be required to keep a pain diary throughout the study to record their level of pain on a daily basis, and will be asked to avoid or restrict the use of specific medications or other remedies to treat the pain.
At the first visit (Week 0), one group will receive a prescribed dose of botulinum toxin A, which will be administered as an injection into the leiomyoma, and the other (control) group will receive a placebo injection of a saline solution. Patients will return 4 weeks later, at which time they will undergo a medical examination, and the ice test, and complete questionnaires to assess responses and level of pain. Patients will return in Week 12, at which time the group assignment will be revealed (un-blinded) to investigators and patients. Patients who received placebo injections will be offered the opportunity to receive injection of botulinum toxin A into their leiomyomas. All patients will undergo a medical examination, the ice test, complete questionnaires, and continue completing their daily pain diaries at home. The final visit, in Week 24, will follow the same procedure as the Week 4 visit.
At the end of the study, patients may be eligible to have one or more of the painful cutaneous leiomyomas surgically removed if the researchers believe that the skin lesions can be removed with a reasonable cosmetic result.
Hereditary Leiomyomatosis and Renal Cell Cancer
Biological: Botulinum toxin type A
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||Randomized Pilot Study for the Treatment of Cutaneous Leiomyomas With Botulinum Toxin|
- Change in Worst Lesional Pain in the Past Week Based on Brief Pain Inventory [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: No ]Change in worst lesional pain in the past week based on Brief Pain Inventory (BPI) from Week 0 to Week 4 in treated patients versus controls. The BPI uses an arbitrary units on a 0-10 scale. For the purposes of the statistical calculation, a difference of 1 standard deviation between groups at baseline vs. week 4 was considered significant. Any BPI value above zero (no pain) is abnormal. The mean change indicates mean change in pain score.
- Number of Participants With Adverse Events [ Time Frame: 37 months ] [ Designated as safety issue: Yes ]Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.
|Study Start Date:||January 2009|
|Estimated Study Completion Date:||June 2015|
|Primary Completion Date:||March 2014 (Final data collection date for primary outcome measure)|
BTX-A intralesional injection
Biological: Botulinum toxin type A
Given as an intralesional injection.
Saline intralesional injection
Given as an intralesional injection
- Cutaneous leiomyomas are smooth muscle tumors that may arise sporadically or in association with an inherited cancer-related genodermatosis.
- Leiomyomas may be severely painful, and current management is generally unsatisfactory.
- Studies demonstrate increased nerve density within and around leiomyomas as well as increased acetylcholinesterase staining of associated nerves.
- Botulinum toxin-A has been used in the treatment of pain syndromes.
- Based on the known mechanisms of action of botulinum toxin-A, treatment with botulinum toxin-A (BOTOX; Allergan, Inc.), may ameliorate the severe paroxysmal pain of symptomatic cutaneous leiomyomas.
- Primary: To assess change in worst lesional pain in the past week based on Brief Pain Inventory (BPI) from Week 0 to Week 4 in treated patients versus controls.
- Primary: To assess improvement in pain based on Visual Analog Scale (VAS) after application of ice at Week 4 compared to baseline in treated patients versus controls.
- Secondary: To assess change in magnitude and in frequency of painful episodes based on a weekly patient diary in treated patients versus controls.
- Secondary: To assess persistence of pain control at Weeks 12 based on the BPI and VAS.
- Secondary: To assess the frequency of rescue pain medication use in treated patients versus controls during the 24 week study period.
- Secondary: To determine the impact of leiomyoma treatment on quality of life.
- Secondary: To assess change in patient s condition based on the Patient Global Impression of Change.
- Secondary: To evaluate the immunohistochemical staining of nerve fibers and muscle in cutaneous leiomyomas in control and treated lesions following the conclusion of the study.
- Subjects greater than or equal to18 years with at least 1 symptomatic cutaneous leiomyoma.
- Pain symptoms must occur at least once a week and be characterized as greater than or equal to 5 out of 10.
- A 12-week double-blind placebo controlled pilot study of 18 subjects with symptomatic leiomyomas will include initial assessment with BPI, photography, and skin biopsies, followed by treatment of subjects who initially received placebo.
- Cutaneous leiomyomas will undergo intralesional injection with botulinum toxin-A.
- Subjects will return at Weeks 4 and 12 for repeat assessment using pain and quality of life questionnaires and photography. Skin biopsies will be performed at week 12.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00971620
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Edward W Cowen, M.D.||National Cancer Institute (NCI)|