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Cutaneous LeiomyomasPhase 2NCT00971620

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

A Phase 2 study testing Botulinum toxin type A in people with Cutaneous Leiomyomas and Hereditary Leiomyomatosis and Renal Cell Cancer, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Botulinum toxin type A
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
18 participants
Where
1 siteUnited States
Study dates
17 Nov 2008to 12 Oct 2016
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subjects must be age greater than or equal to18 years.
  • Subjects must have a prior biopsy-proven diagnosis of cutaneous leiomyoma.
  • 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.
  • Pain episodes must occur at least once a week.
  • Subjects must have the ability to participate fully and comply with the procedures of the protocol in the opinion of the investigator.
  • Written informed consent has been obtained including consenting to have tissue samples stored, however subjects are allowed to refuse sample storage.
  • Negative urine or serum pregnancy test in females of childbearing potential.
  • Subjects who are clinically stable such that they can be expected to complete the 24-week study.

Who cannot join

  • Subjects with allergies to BTX-A.
  • 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.
  • Subjects with neuromuscular junction disorders (ie. myasthenia gravis or Lambert-Eaton syndrome) or peripheral motor neuropathic diseases (ie. amyotrophic lateral sclerosis or motor neuropathy).
  • Subjects with infection at the intended sites of injection.
  • Subjects who have had prior Botulinum toxin product within the past 6 months.
  • Subjects with pain resulting from other disease(s), specifically:
Show all 11Show fewer
  • pain that requires intermittent or ongoing treatment with narcotics
  • severe, debilitating, or acute pain originating from sources other than leiomyomas
  • 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.
  • 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).
  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

Other trials in United States

About this study

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.

Read more

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.

Read the detailed description

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 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.

Eligibility:

  • 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.

Design:

  • 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.
Being tested
Botulinum toxin type A, Placebo
Keywords
Cutaneous Leiomyomas, Skin Pain, Botox Therapy, Hereditary Leiomyomatosis, Renal Cell Cancer, Cutaneous Leiomyoma
Medical subject headings
Hereditary leiomyomatosis and renal cell cancer, Carcinoma, Renal Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Botulinum toxin type ABiological

    Also called BTX-A

    Given as an intralesional injection.

  • PlaceboOther

    Given as an intralesional injection

Study groups in NCT00971620
Study groupRoleWhat they receive
BTX-AExperimentalBTX-A intralesional injection
Receives: Biological: Botulinum toxin type A
Placebo/SalineExperimentalSaline intralesional injection
Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in Worst Lesional Pain in the Past Week Based on Brief Pain Inventory

    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.

    Measured: Between week 0 and week 4

  2. Median Change in Average Pain Between Two Arms

    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)).

    Measured: Between weeks 0 and week 4

Secondary outcomes (11)

  1. Number of Participants With Adverse Events

    Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.

    Measured: 37 months

  2. Visual Analog Scale (VAS) of Patient Perceived Pain at Leiomyoma Site Prior to Ice Provocation at 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.

    Measured: Week 0 vs. week 4

  3. Comparison of Change in Skin Related Quality of Life by Total Dermatology Life Quality Index (DLQI) at 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.

    Measured: Week 0 vs. week 4

  4. Specific Skin Pain-Related Question on the Dermatology Life Quality Index

    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.

    Measured: Week 0 vs. week 4

  5. Change in Post-Ice Provocation Visual Analog Score (VAS) Between Week 12 and Week 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.

    Measured: Between week 12 and 24

  6. Immunohistochemical Staining of Cutaneous Leiomyomas for Acetylcholinesterase (AchE) Before (i.e.,Week 0) and 12 Weeks After Botulinum Toxin Administration

    AchE staining was scored as 0 (none), 1 (rare), 2 (scattered), or 3 (focal or greater).

    Measured: Week 0 vs. week 12

  7. Immunohistochemical Staining of Cutaneous Leiomyomas for C-fos Before (i.e., Week 0) and 12 Weeks After Botulinum Toxin Administration

    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).

    Measured: Week 0 vs. week 12

  8. Percentage of Patients With a Change in Average Pain Score

    Average pain was determined from a 0-10 scale question on the Brief Pain Inventory (BPI). 10 denotes worse pain.

    Measured: Week 0 score vs. week 4 score

  9. Percentage of Patients With a Change in Pre-Ice Visual Analog Score (VAS) Between Week 0 and 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.

    Measured: Week 0 vs. week 4

  10. Percentage of Patients With a Change in Post-Ice Visual Analog Score (VAS) Between Week 0 and 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.

    Measured: Week 0 vs. week 4

  11. Worst Pain Severity

    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.

    Measured: Week 0 vs. week 4

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Sep 2009 (estimated)
  2. Study start17 Nov 2008
  3. Primary completion9 Jan 2014
  4. Study completion12 Oct 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Single group
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00971620
Sponsor's protocol ID
090072
Other IDs
09-C-0072
Status last verified
Feb 2017
First submitted
3 Sep 2009
Last updated
7 Apr 2017
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Archer CB, Whittaker S, Greaves MW. Pharmacological modulation of cold-induced pain in cutaneous leiomyomata. Br J Dermatol. 1988 Feb;118(2):255-60. doi: 10.1111/j.1365-2133.1988.tb01783.x.

    PubMed 3348971

  • Batchelor RJ, Lyon CC, Highet AS. Successful treatment of pain in two patients with cutaneous leiomyomata with the oral alpha-1 adrenoceptor antagonist, doxazosin. Br J Dermatol. 2004 Apr;150(4):775-6. doi: 10.1111/j.0007-0963.2004.05880.x. No abstract available.

    PubMed 15099382

  • Raj S, Calonje E, Kraus M, Kavanagh G, Newman PL, Fletcher CD. Cutaneous pilar leiomyoma: clinicopathologic analysis of 53 lesions in 45 patients. Am J Dermatopathol. 1997 Feb;19(1):2-9. doi: 10.1097/00000372-199702000-00002.

    PubMed 9056647

  • Naik HB, Steinberg SM, Middelton LA, Hewitt SM, Zuo RC, Linehan WM, Kong HH, Cowen EW. Efficacy of Intralesional Botulinum Toxin A for Treatment of Painful Cutaneous Leiomyomas: A Randomized Clinical Trial. JAMA Dermatol. 2015 Oct;151(10):1096-102. doi: 10.1001/jamadermatol.2015.1793.

    PubMed 26244563

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Botulinum toxin type A in people with Cutaneous Leiomyomas and Hereditary Leiomyomatosis and Renal Cell Cancer, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Jan 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Worst Lesional Pain in the Past Week Based on Brief Pain Inventory (time frame: Between week 0 and week 4). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00971620, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Apr 2017.

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