Clinical Trial: Randomized Pilot Study for the Treatment of Cutaneous Leiomyomas With Botulinum Toxin

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Randomized Pilot Study for the Treatment of Cutaneous Leiomyomas With Botulinum Toxin

Brief Summary:

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

Detailed Summary:

Background:

  • 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.

Objectives:

  • 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 treatmen
    Sponsor: National Cancer Institute (NCI)

    Current Primary Outcome:

    • Change in Worst Lesional Pain in the Past Week Based on Brief Pain Inventory [ Time Frame: Between week 0 and week 4 ]
      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.
    • Median Change in Average Pain Between Two Arms [ Time Frame: Between weeks 0 and week 4 ]
      Change in average pain was assessed by the Brief Pain Inventory (BPI). The BPI is a validated pain assessment tool that assesses severity of pain, location of pain, impact of pain on daily functions, pain medications, and amount of pain relief in the past 24 hours or past week (e.g. scale of 0-10 (worst pain)).


    Original Primary Outcome: To access change in worst lesional pain in the past week based on Brief Pain Inventory (BPI) in treated patients versus controls, and to assess improvement in pain based on Visual Analog Scale (VAS) after application of ice from Week 0 to Week 4.

    Current Secondary Outcome:

    • Number of Participants With Adverse Events [ Time Frame: 37 months ]
      Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.
    • Visual Analog Scale (VAS) of Patient Perceived Pain at Leiomyoma Site Prior to Ice Provocation at Week 0 vs. Week 4 [ Time Frame: Week 0 vs. week 4 ]
      The VAS is a commonly used validated tool for assessment of pain. For this measure, a 10-cm VAS was used to assess current patient pain/discomfort before application of ice to study lesions at week 0 and week 4. A clinically meaningful change in chronic pain intensity using the VAS has been determined as a reduction of 2 points or 30%. Range is 0-10; 0 is no pain and 10 is worst possible pain.
    • Comparison of Change in Skin Related Quality of Life by Total Dermatology Life Quality Index (DLQI) at Week 0 vs. Week 4 [ Time Frame: Week 0 vs. week 4 ]
      The DLQI is a 10-question quality of life survey which has been extensively validated and frequently used in dermatologic disorders such as atopic dermatitis, acne, and psoriasis. Score is 0-30 based on 10 questions. The higher the score, the more quality of life is impaired.
    • Specific Skin Pain-Related Question on the Dermatology Life Quality Index [ Time Frame: Week 0 vs. week 4 ]
      The DLQI is a 10-question quality of life survey which has been extensively validated and frequently used in dermatologic disorders such as atopic dermatitis, acne, and psoriasis. Participants response to the question "Over the last week, how itchy, sore, painful or stinging has your skin been?" was assessed by the Dermatology Life Quality Index. This outcome refers to a single specific question on the DLQI, so the range for this outcome is 0-3. Lower values in the DLQI indicate less impairment (or greater improvement) in life quality from the skin disease.
    • Change in Post-Ice Provocation Visual Analog Score (VAS) Between Week 12 and Week 24 [ Time Frame: Between week 12 and 24 ]
      The VAS is a commonly used validated tool for assessment of pain. The 10-cm VAS was used to assess current patient pain/discomfort before and after application of ice to study lesions. A clinically meaningful change in chronic pain intensity using the VAS has been determined as a reduction of 2 points or 30%. Scale is 0-10. 10 denotes worse pain than 0.
    • Immunohistochemical Staining of Cutaneous Leiomyomas for Acetylcholinesterase (AchE) Before (i.e.,Week 0) and 12 Weeks After Botulinum Toxin Administration [ Time Frame: Week 0 vs. week 12 ]
      AchE staining was scored as 0 (none), 1 (rare), 2 (scattered), or 3 (focal or greater).
    • Immunohistochemical Staining of Cutaneous Leiomyomas for C-fos Before (i.e., Week 0) and 12 Weeks After Botulinum Toxin Administration [ Time Frame: Week 0 vs. week 12 ]
      c-fos, a marker of neuronal activation after pain stimulation, was scored as 0 (none), 1 (scattered), 2 (<66% of tumor cells), or 3 (≥66% of tumor cells).
    • Percentage of Patients With a Change in Average Pain Score [ Time Frame: Week 0 score vs. week 4 score ]
      Average pain was determined from a 0-10 scale question on the Brief Pain Inventory (BPI). 10 denotes worse pain.
    • Percentage of Patients With a Change in Pre-Ice Visual Analog Score (VAS) Between Week 0 and Week 4 [ Time Frame: Week 0 vs. week 4 ]
      The VAS is a commonly used validated tool for assessment of pain. The 10-cm VAS was used to assess current patient pain/discomfort before and after application of ice to study lesions. A clinically meaningful change in chronic pain intensity using the VAS has been determined as a reduction of 2 points or 30%. Scale of 0-10. 10 = worse pain.
    • Percentage of Patients With a Change in Post-Ice Visual Analog Score (VAS) Between Week 0 and Week 4 [ Time Frame: Week 0 vs. week 4 ]
      The VAS is a commonly used validated tool for assessment of pain. The 10-cm VAS was used to assess current patient pain/discomfort before and after application of ice to study lesions. A clinically meaningful change in chronic pain intensity using the VAS has been determined as a reduction of 2 points or 30%. Scale is 0-10. 10 = worse pain.
    • Worst Pain Severity [ Time Frame: Week 0 vs. week 4 ]
      Pain severity was assessed by the Brief Pain Inventory (BPI). The BPI is a validated pain assessment tool that assesses severity of pain, location of pain, impact of pain on daily functions, pain medications, and amount of pain relief in the past 24 hours or past week (e.g. scale of 0-10 (worst pain)). This outcome was based on a single 0-10 question on the BPI.


    Original Secondary Outcome: To evaluate the immunohistochemical staining of nerve fibers and muscle in cutaneous leiomyomas in control and treated lesions following the conclusion of the study.

    Information By: National Institutes of Health Clinical Center (CC)

    Dates:
    Date Received: September 3, 2009
    Date Started: November 17, 2008
    Date Completion:
    Last Updated: February 23, 2017
    Last Verified: February 2017