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

NCT00971620 | Completed Phase 2 Results

• 2 other identifiers: 09007209-C-0072
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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 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.

Conditions

Cutaneous Leiomyomas; Hereditary Leiomyomatosis and Renal Cell Cancer

Keywords

Cutaneous Leiomyomas; Skin Pain; Botox Therapy; Hereditary Leiomyomatosis; Renal Cell Cancer; Cutaneous Leiomyoma

Outcome Measures

Primary Outcomes (2)

• 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.

  Between week 0 and week 4

• 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)).

  Between weeks 0 and week 4

Secondary Outcomes (11)

• Number of Participants With Adverse Events

  37 months

• Visual Analog Scale (VAS) of Patient Perceived Pain at Leiomyoma Site Prior to Ice Provocation at Week 0 vs. Week 4

  Week 0 vs. week 4

• Comparison of Change in Skin Related Quality of Life by Total Dermatology Life Quality Index (DLQI) at Week 0 vs. Week 4

  Week 0 vs. week 4

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

  Week 0 vs. week 4

• Change in Post-Ice Provocation Visual Analog Score (VAS) Between Week 12 and Week 24

  Between week 12 and 24

Study Arms (2)

BTX-A

EXPERIMENTAL

BTX-A intralesional injection

Biological: Botulinum toxin type A

Placebo/Saline

EXPERIMENTAL

Saline intralesional injection

Other: Placebo

Interventions

Botulinum toxin type A BIOLOGICAL

Given as an intralesional injection.

Also known as: BTX-A

BTX-A

Placebo OTHER

Given as an intralesional injection

Placebo/Saline

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• pain that requires intermittent or ongoing treatment with narcotics
• severe, debilitating, or acute pain originating from sources other than leiomyomas
• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• 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.

  PMID: 3348971 BACKGROUND

• 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.

  PMID: 15099382 BACKGROUND

• 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.

  PMID: 9056647 BACKGROUND

• 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.

  PMID: 26244563 RESULT

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Hereditary leiomyomatosis and renal cell cancer; Carcinoma, Renal Cell

Interventions

Botulinum Toxins, Type A

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Botulinum Toxins; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Bacterial Toxins; Toxins, Biological; Biological Factors

Results Point of Contact

• Title: Dr. Edward Cowen
• Organization: National Cancer Institute

cowene@mail.nih.gov

301-496-4299

Study Officials

• Edward W Cowen, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 3, 2009
• First Posted: September 4, 2009
• Study Start: November 17, 2008
• Primary Completion: January 9, 2014
• Study Completion: October 12, 2016
• Last Updated: April 7, 2017
• Results First Posted: January 6, 2015

Record last verified: 2017-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)