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NCT00971620

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

Completed Phase 2 Results posted Last updated 7 April 2017
What this trial tests

Phase 2 trial testing Botulinum toxin type A in Cutaneous Leiomyomas in 18 participants. Completed in 12 October 2016.

Timeline
17 November 2008
Primary endpoint
9 January 2014
12 October 2016

Quick facts

Lead sponsorNational Cancer Institute (NCI)
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designsingle group
Maskingdouble
Primary purposetreatment
Enrollment18
Start date17 November 2008
Primary completion9 January 2014
Estimated completion12 October 2016
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

National Cancer Institute (NCI)

Who can join

18 and older, any sex, with Cutaneous Leiomyomas or Hereditary Leiomyomatosis and Renal Cell Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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

GroupValue95% CI
BTX-A-2.50± 0.46
Placebo/Saline-1.26± 0.53
Median Change in Average Pain Between Two Arms Primary · 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)).

GroupValue95% CI
BTX-A0.00-6.00 – 2.00
Placebo/Saline0.00-5.00 – 3.00
Number of Participants With Adverse Events Secondary · 37 months

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

GroupValue95% CI
BTX-A4
Placebo/Saline5
Visual Analog Scale (VAS) of Patient Perceived Pain at Leiomyoma Site Prior to Ice Provocation at Week 0 vs. Week 4 Secondary · 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.

GroupValue95% CI
BTX-A0.00-3.30 – 0.70
Placebo/Saline0.40-1.30 – 1.50
Comparison of Change in Skin Related Quality of Life by Total Dermatology Life Quality Index (DLQI) at Week 0 vs. Week 4 Secondary · 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.

GroupValue95% CI
BTX-A-4.00-8.00 – 2.00
Placebo/Saline0.00-1.00 – 4.00
Specific Skin Pain-Related Question on the Dermatology Life Quality Index Secondary · 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.

GroupValue95% CI
BTX-A-1.00-2.00 – 1.00
Placebo/Saline0.00-1.00 – 0.00
Change in Post-Ice Provocation Visual Analog Score (VAS) Between Week 12 and Week 24 Secondary · 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.

GroupValue95% CI
BTX-A4.102.50 – 5.90
Placebo/Saline-0.30-8.50 – 1.10
Immunohistochemical Staining of Cutaneous Leiomyomas for Acetylcholinesterase (AchE) Before (i.e.,Week 0) and 12 Weeks After Botulinum Toxin Administration Secondary · Week 0 vs. week 12

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

GroupValue95% CI
BTX-A1.000.00 – 2.00
Placebo/Saline0.00-1.00 – 0.00
Immunohistochemical Staining of Cutaneous Leiomyomas for C-fos Before (i.e., Week 0) and 12 Weeks After Botulinum Toxin Administration Secondary · 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).

GroupValue95% CI
BTX-A-1.00-1.00 – 0.00
Placebo/Saline0.000.00 – 1.00
Percentage of Patients With a Change in Average Pain Score Secondary · 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.

>50% pain reduction
GroupValue95% CI
BTX-A44
Placebo/Saline22
≤50% pain reduction
GroupValue95% CI
BTX-A0
Placebo/Saline11
No change in pain
GroupValue95% CI
BTX-A22
Placebo/Saline33
Increased pain
GroupValue95% CI
BTX-A22
Placebo/Saline22
Missing
GroupValue95% CI
BTX-A11
Placebo/Saline11
Percentage of Patients With a Change in Pre-Ice Visual Analog Score (VAS) Between Week 0 and Week 4 Secondary · 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.

>50% pain reduction
GroupValue95% CI
BTX-A22
Placebo/Saline11
≤50% pain reduction
GroupValue95% CI
BTX-A33
Placebo/Saline0
No change in pain
GroupValue95% CI
BTX-A0
Placebo/Saline11
Increased pain
GroupValue95% CI
BTX-A11
Placebo/Saline55
Missing
GroupValue95% CI
BTX-A33
Placebo/Saline22
Percentage of Patients With a Change in Post-Ice Visual Analog Score (VAS) Between Week 0 and Week 4 Secondary · 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.

>50% pain reduction
GroupValue95% CI
BTX-A33
Placebo/Saline33
≤50% pain reduction
GroupValue95% CI
BTX-A44
Placebo/Saline44
No change in pain
GroupValue95% CI
BTX-A0
Placebo/Saline0
Increased pain
GroupValue95% CI
BTX-A22
Placebo/Saline22
Missing
GroupValue95% CI
BTX-A0
Placebo/Saline0

Adverse events — posted to ClinicalTrials.gov

Time frame: 37 months. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

BTX-A
Serious: 0/9 (0%)
Deaths: 0/9
Placebo/Saline
Serious: 0/9 (0%)
Deaths: 0/9
Other adverse events (15 terms — click to expand)

ReactionSystemBTX-APlacebo/Saline
Pain - Other (Specify, __)Musculoskeletal and connective tissue disorders
Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)Immune system disorders
Constitutional Symptoms - Other (Specify, __)General disorders
FractureMusculoskeletal and connective tissue disorders
HypertensionCardiac disorders
Infection with normal ANC or Grade 1 or 2 neutrophils::BronchusInfections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils::SinusInfections and infestations
Infection with unknown ANC::Upper airway NOSInfections and infestations
Nasal cavity/paranasal sinus reactionsRespiratory, thoracic and mediastinal disorders
NauseaGastrointestinal disorders
Pain::BackMusculoskeletal and connective tissue disorders
Pain::BoneMusculoskeletal and connective tissue disorders
Pain::Head/headacheNervous system disorders
Pain::Pain NOSGeneral disorders
VomitingGastrointestinal disorders

Data from ClinicalTrials.gov NCT00971620 adverse events section.

Sponsor's own description

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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

  1. Efficacy of Intralesional Botulinum Toxin A for Treatment of Painful Cutaneous Leiomyomas: A Randomized Clinical Trial.
    Naik HB, Steinberg SM, Middelton LA, Hewitt SM, et al · · 2015 · cited 15× · PMID 26244563 · DOI 10.1001/jamadermatol.2015.1793

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