Trial Outcomes & Findings for Randomized Pilot Study for the Treatment of Cutaneous Leiomyomas With Botulinum Toxin (NCT NCT00971620)

Last Updated: 2017-04-07

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

18 participants

Primary outcome timeframe

Between week 0 and week 4

Results posted on

2017-04-07

Participant Flow

Participant milestones

Participant milestones
Measure	BTX-A BTX-A intralesional injection	Placebo/Saline Saline intralesional injection
Overall Study STARTED	9	9
Overall Study COMPLETED	9	9
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	BTX-A n=9 Participants BTX-A intralesional injection	Placebo/Saline n=9 Participants Saline intralesional injection	Total n=18 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	8 Participants n=5 Participants	9 Participants n=7 Participants	17 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Age, Continuous	48.4 years STANDARD_DEVIATION 15.6 • n=5 Participants	45.5 years STANDARD_DEVIATION 11.4 • n=7 Participants	47.0 years STANDARD_DEVIATION 13.8 • n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	6 Participants n=7 Participants	14 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=5 Participants	9 Participants n=7 Participants	18 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	9 Participants n=5 Participants	9 Participants n=7 Participants	18 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	9 Participants n=5 Participants	9 Participants n=7 Participants	18 Participants n=5 Participants
Leiomyoma Distribution Single	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Leiomyoma Distribution Segmental	7 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants
Leiomyoma Distribution Disseminated	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Location of Lesions Neck	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Location of Lesions Torso	6 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants
Location of Lesions Extremity	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Volume of Drug Administered	2.41 mL STANDARD_DEVIATION 0.70 • n=5 Participants	1.12 mL STANDARD_DEVIATION 0.38 • n=7 Participants	1.76 mL STANDARD_DEVIATION .54 • n=5 Participants

PRIMARY outcome

Timeframe: Between week 0 and week 4

Outcome measures

Outcome measures
Measure	BTX-A n=9 Participants BTX-A intralesional injection	Placebo/Saline n=9 Participants Saline intralesional injection
Change in Worst Lesional Pain in the Past Week Based on Brief Pain Inventory	-2.50 units on a scale Standard Error 0.46	-1.26 units on a scale Standard Error 0.53

PRIMARY outcome

Timeframe: 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)).

Outcome measures

Outcome measures
Measure	BTX-A n=9 Participants BTX-A intralesional injection	Placebo/Saline n=9 Participants Saline intralesional injection
Median Change in Average Pain Between Two Arms	0.00 Score Interval -6.0 to 2.0	0.00 Score Interval -5.0 to 3.0

SECONDARY outcome

Timeframe: 37 months

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

Outcome measures

Outcome measures
Measure	BTX-A n=9 Participants BTX-A intralesional injection	Placebo/Saline n=9 Participants Saline intralesional injection
Number of Participants With Adverse Events	4 participants	5 participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	BTX-A n=9 Participants BTX-A intralesional injection	Placebo/Saline n=9 Participants Saline intralesional injection
Visual Analog Scale (VAS) of Patient Perceived Pain at Leiomyoma Site Prior to Ice Provocation at Week 0 vs. Week 4	0.00 Score Interval -3.3 to 0.7	0.40 Score Interval -1.3 to 1.5

SECONDARY outcome

Timeframe: Week 0 vs. week 4

Outcome measures

Outcome measures
Measure	BTX-A n=9 Participants BTX-A intralesional injection	Placebo/Saline n=9 Participants Saline intralesional injection
Comparison of Change in Skin Related Quality of Life by Total Dermatology Life Quality Index (DLQI) at Week 0 vs. Week 4	-4.00 Units on a scale Interval -8.0 to 2.0	0.00 Units on a scale Interval -1.0 to 4.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	BTX-A n=9 Participants BTX-A intralesional injection	Placebo/Saline n=9 Participants Saline intralesional injection
Specific Skin Pain-Related Question on the Dermatology Life Quality Index	-1.00 Units on a scale Interval -2.0 to 1.0	0.00 Units on a scale Interval -1.0 to 0.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	BTX-A n=9 Participants BTX-A intralesional injection	Placebo/Saline n=9 Participants Saline intralesional injection
Change in Post-Ice Provocation Visual Analog Score (VAS) Between Week 12 and Week 24	4.10 Score Interval 2.5 to 5.9	-0.30 Score Interval -8.5 to 1.1

SECONDARY outcome

Timeframe: Week 0 vs. week 12

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

Outcome measures

Outcome measures
Measure	BTX-A n=9 Participants BTX-A intralesional injection	Placebo/Saline n=9 Participants Saline intralesional injection
Immunohistochemical Staining of Cutaneous Leiomyomas for Acetylcholinesterase (AchE) Before (i.e.,Week 0) and 12 Weeks After Botulinum Toxin Administration	1.00 Score Interval 0.0 to 2.0	0.00 Score Interval -1.0 to 0.0

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	BTX-A n=9 Participants BTX-A intralesional injection	Placebo/Saline n=9 Participants Saline intralesional injection
Immunohistochemical Staining of Cutaneous Leiomyomas for C-fos Before (i.e., Week 0) and 12 Weeks After Botulinum Toxin Administration	-1.00 Score Interval -1.0 to 0.0	0.00 Score Interval 0.0 to 1.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	BTX-A n=9 Participants BTX-A intralesional injection	Placebo/Saline n=9 Participants Saline intralesional injection
Percentage of Patients With a Change in Average Pain Score >50% pain reduction	44 percentage of patients	22 percentage of patients
Percentage of Patients With a Change in Average Pain Score ≤50% pain reduction	0 percentage of patients	11 percentage of patients
Percentage of Patients With a Change in Average Pain Score No change in pain	22 percentage of patients	33 percentage of patients
Percentage of Patients With a Change in Average Pain Score Increased pain	22 percentage of patients	22 percentage of patients
Percentage of Patients With a Change in Average Pain Score Missing	11 percentage of patients	11 percentage of patients

SECONDARY outcome

Timeframe: Week 0 vs. week 4

Outcome measures

Outcome measures
Measure	BTX-A n=9 Participants BTX-A intralesional injection	Placebo/Saline n=9 Participants Saline intralesional injection
Percentage of Patients With a Change in Pre-Ice Visual Analog Score (VAS) Between Week 0 and Week 4 >50% pain reduction	22 percentage of patients	11 percentage of patients
Percentage of Patients With a Change in Pre-Ice Visual Analog Score (VAS) Between Week 0 and Week 4 ≤50% pain reduction	33 percentage of patients	0 percentage of patients
Percentage of Patients With a Change in Pre-Ice Visual Analog Score (VAS) Between Week 0 and Week 4 No change in pain	0 percentage of patients	11 percentage of patients
Percentage of Patients With a Change in Pre-Ice Visual Analog Score (VAS) Between Week 0 and Week 4 Increased pain	11 percentage of patients	55 percentage of patients
Percentage of Patients With a Change in Pre-Ice Visual Analog Score (VAS) Between Week 0 and Week 4 Missing	33 percentage of patients	22 percentage of patients

SECONDARY outcome

Timeframe: Week 0 vs. week 4

Outcome measures

Outcome measures
Measure	BTX-A n=9 Participants BTX-A intralesional injection	Placebo/Saline n=9 Participants Saline intralesional injection
Percentage of Patients With a Change in Post-Ice Visual Analog Score (VAS) Between Week 0 and Week 4 >50% pain reduction	33 percentage of patients	33 percentage of patients
Percentage of Patients With a Change in Post-Ice Visual Analog Score (VAS) Between Week 0 and Week 4 ≤50% pain reduction	44 percentage of patients	44 percentage of patients
Percentage of Patients With a Change in Post-Ice Visual Analog Score (VAS) Between Week 0 and Week 4 No change in pain	0 percentage of patients	0 percentage of patients
Percentage of Patients With a Change in Post-Ice Visual Analog Score (VAS) Between Week 0 and Week 4 Increased pain	22 percentage of patients	22 percentage of patients
Percentage of Patients With a Change in Post-Ice Visual Analog Score (VAS) Between Week 0 and Week 4 Missing	0 percentage of patients	0 percentage of patients

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	BTX-A n=9 Participants BTX-A intralesional injection	Placebo/Saline n=9 Participants Saline intralesional injection
Worst Pain Severity	-2.25 Score Interval -5.0 to 0.25	-0.75 Score Interval -3.75 to 0.5

Adverse Events

BTX-A

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Placebo/Saline

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Dr. Edward Cowen

National Cancer Institute

Phone: 301-496-4299

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	BTX-A n=9 participants at risk BTX-A intralesional injection	Placebo/Saline n=9 participants at risk Saline intralesional injection
Immune system disorders Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)	0.00% 0/9 • 37 months There are no unexpected adverse events at grade 2 or higher.	11.1% 1/9 • Number of events 1 • 37 months There are no unexpected adverse events at grade 2 or higher.
General disorders Constitutional Symptoms - Other (Specify, __)	11.1% 1/9 • Number of events 1 • 37 months There are no unexpected adverse events at grade 2 or higher.	11.1% 1/9 • Number of events 1 • 37 months There are no unexpected adverse events at grade 2 or higher.
Musculoskeletal and connective tissue disorders Fracture	0.00% 0/9 • 37 months There are no unexpected adverse events at grade 2 or higher.	11.1% 1/9 • Number of events 1 • 37 months There are no unexpected adverse events at grade 2 or higher.
Cardiac disorders Hypertension	11.1% 1/9 • Number of events 1 • 37 months There are no unexpected adverse events at grade 2 or higher.	11.1% 1/9 • Number of events 1 • 37 months There are no unexpected adverse events at grade 2 or higher.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils::Bronchus	11.1% 1/9 • Number of events 1 • 37 months There are no unexpected adverse events at grade 2 or higher.	0.00% 0/9 • 37 months There are no unexpected adverse events at grade 2 or higher.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils::Sinus	0.00% 0/9 • 37 months There are no unexpected adverse events at grade 2 or higher.	11.1% 1/9 • Number of events 1 • 37 months There are no unexpected adverse events at grade 2 or higher.
Infections and infestations Infection with unknown ANC::Upper airway NOS	11.1% 1/9 • Number of events 1 • 37 months There are no unexpected adverse events at grade 2 or higher.	0.00% 0/9 • 37 months There are no unexpected adverse events at grade 2 or higher.
Respiratory, thoracic and mediastinal disorders Nasal cavity/paranasal sinus reactions	0.00% 0/9 • 37 months There are no unexpected adverse events at grade 2 or higher.	11.1% 1/9 • Number of events 1 • 37 months There are no unexpected adverse events at grade 2 or higher.
Gastrointestinal disorders Nausea	11.1% 1/9 • Number of events 1 • 37 months There are no unexpected adverse events at grade 2 or higher.	0.00% 0/9 • 37 months There are no unexpected adverse events at grade 2 or higher.
Musculoskeletal and connective tissue disorders Pain - Other (Specify, __)	22.2% 2/9 • Number of events 2 • 37 months There are no unexpected adverse events at grade 2 or higher.	22.2% 2/9 • Number of events 2 • 37 months There are no unexpected adverse events at grade 2 or higher.
Musculoskeletal and connective tissue disorders Pain::Back	0.00% 0/9 • 37 months There are no unexpected adverse events at grade 2 or higher.	11.1% 1/9 • Number of events 1 • 37 months There are no unexpected adverse events at grade 2 or higher.
Musculoskeletal and connective tissue disorders Pain::Bone	0.00% 0/9 • 37 months There are no unexpected adverse events at grade 2 or higher.	11.1% 1/9 • Number of events 1 • 37 months There are no unexpected adverse events at grade 2 or higher.
Nervous system disorders Pain::Head/headache	11.1% 1/9 • Number of events 1 • 37 months There are no unexpected adverse events at grade 2 or higher.	0.00% 0/9 • 37 months There are no unexpected adverse events at grade 2 or higher.
General disorders Pain::Pain NOS	11.1% 1/9 • Number of events 1 • 37 months There are no unexpected adverse events at grade 2 or higher.	11.1% 1/9 • Number of events 1 • 37 months There are no unexpected adverse events at grade 2 or higher.
Gastrointestinal disorders Vomiting	11.1% 1/9 • Number of events 1 • 37 months There are no unexpected adverse events at grade 2 or higher.	0.00% 0/9 • 37 months There are no unexpected adverse events at grade 2 or higher.