Randomized Pilot Study for the Treatment of Cutaneous Leiomyomas With Botulinum Toxin
Condition: Cutaneous Leiomyomas; Hereditary Leiomyomatosis and Renal Cell Cancer
MeSH terms: Carcinoma, Renal Cell; Leiomyoma; Myofibroma; Leiomyomatosis
Intervention: Botulinum toxin type A; Placebo
Intervention description: Given as an intralesional injection.; Given as an intralesional injection
Intervention MeSH terms: Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Double (Participant, Investigator)
Enrollment: 18.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Cutaneous Leiomyomas; Skin Pain; Botox Therapy; Hereditary Leiomyomatosis; Renal Cell Cancer; Cutaneous Leiomyoma

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 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.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

               1. Subjects must be age greater than or equal to18 years.

               2. Subjects must have a prior biopsy-proven diagnosis of cutaneous leiomyoma.

               3. Subjects must have at least 1 symptomatic leiomyomas or regions less than or
                  equal to 60 cm^2 of leiomyomas with pain characterized as greater than 4 based on
                  a 10-point scale, indicating pain of at least moderate severity.

               4. Pain episodes must occur at least once a week.

               5. Subjects must have the ability to participate fully and comply with the
                  procedures of the protocol in the opinion of the investigator.

               6. Written informed consent has been obtained including consenting to have tissue
                  samples stored, however subjects are allowed to refuse sample storage.

               7. Negative urine or serum pregnancy test in females of childbearing potential.

               8. Subjects who are clinically stable such that they can be expected to complete the
                  24-week study.

        EXCLUSION CRITERIA:

          1. Subjects with allergies to BTX-A.

          2. Females with a positive pregnancy test, or who are breast-feeding, planning a
             pregnancy during the study, who think that they may be pregnant at the start of the
             study or females of childbearing potential who are unable or unwilling to use a
             reliable form of contraception during the study.

          3. Subjects with neuromuscular junction disorders (ie. myasthenia gravis or Lambert-Eaton
             syndrome) or peripheral motor neuropathic diseases (ie. amyotrophic lateral sclerosis
             or motor neuropathy).

          4. Subjects with infection at the intended sites of injection.

          5. Subjects who have had prior Botulinum toxin product within the past 6 months.

          6. Subjects with pain resulting from other disease(s), specifically:

               -  pain that requires intermittent or ongoing treatment with narcotics

               -  severe, debilitating, or acute pain originating from sources other than
                  leiomyomas

          7. Subjects taking pain medications, neuroactive agents, or other therapy directed toward
             treatment of cutaneous leiomyomas concurrently or within 5 days or 5 half-lives
             (whichever is longer) of BTX-A treatment, other than specified rescue pain
             medications). Patients currently on therapy directed toward OTHER mild to moderate
             chronic pain will be evaluated on a case-by-case basis for inclusion. Patients with
             well-controlled mild to moderate chronic pain such as that associated with
             osteoarthritis, who do not require narcotic therapy, will NOT be excluded. Aspirin for
             pain relief or for other indications is also acceptable.

          8. Subjects with late-stage cancers or unstable disease (such as hemodynamic instability,
             i.e., systolic or diastolic blood pressure fall of 20 mm Hg or greater from the stable
             patient s baseline measurement).

          9. A condition or situation that, in the investigator's opinion, may put the subject at
             significant risk or interfere significantly with the subject's participation in the
             study.