Botulinum Toxin for Pelvic Pain in Women With Endometriosis

• ClinicalTrials.gov Identifier: NCT01553201
• Recruitment Status: Completed
• First Posted: March 14, 2012
• Results First Posted: July 8, 2020
• Last Update Posted: July 28, 2020
• Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)
• Information provided by (Responsible Party): National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )

Study Description

Brief Summary:

Background:

- Some women with endometriosis have chronic pelvic pain. This pain may be caused by spasms of the pelvic floor muscles. These spasms can be detected by an examination. Studies suggest that botulinum toxin can help treat problems caused by muscle spasms. Researchers want to see if botulinum toxin injections into the pelvic floor muscles can decrease pain and spasms in women with pelvic pain.

Objectives:

- To see if botulinum toxin can relieve pain from pelvic floor spasm in women with pelvic pain.

Eligibility:

- Women between 18 and 50 years of age with pain associated with pelvic muscle spasm and endometriosis. Pain must be persistent (lasting for at least 3 months).

Design:

• Participants will keep a pain diary and record their pain medication use for a month before the first visit.
• Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. Participants will also answer questions about their pain levels and quality of life.
• Participants will receive either botulinum toxin or a placebo (salt water) injection. The injection will be given into the pelvic floor muscles through the vaginal wall. Participants will take a muscle relaxant like Valium and have anesthetic cream put on the vaginal wall before the injection.
• After the injection, participants will keep a pain diary for another month.
• At a 1-month followup visit, participants will answer questions about their pain. If the pain has not improved, all participants may have a botulinum toxin injection (no placebo) into the pelvic floor muscles as before.
• Participants will have followup visits for up to a year after the initial 1-month followup visit.

Condition or disease	Intervention/treatment	Phase
Endometriosis; Chronic Pelvic Pain; Pelvic Muscle Spasm; Quality of Life	Drug: Botulinum toxin (BoNT); Drug: Placebo	Phase 1; Phase 2

Detailed Description:

Chronic pelvic pain associated with endometriosis is poorly understood. Some women with chronic pelvic pain have muscle spasm of their pelvic muscles. Muscle spasm may be a significant part of pain in women with endometriosis and other types of chronic pelvic pain. Botulinum toxin injection is widely used to treat conditions associated with excessive muscle activity and spasm. Studies of botulinum toxin injected into pelvic muscles of women with pelvic pain have shown a decrease pain and spasm, but too few women have been studied to conclude its effectiveness. We expect to show that botulinum toxin injection in women with pelvic pain will relieve some of their pelvic pain.

Eligible subjects will be otherwise healthy women who have chronic pelvic pain and a history of endometriosis. Subjects will be randomized to either botulinum toxin injection or placebo (salt water) injection. After one month, we will evaluate the presence of the pain and all women will be offered botulinum toxin injection. We will also evaluate the need for reinjection.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: The Effectiveness of Botulinum Toxin on Persistent Pelvic Pain in Women With Endometriosis
• Actual Study Start Date: July 30, 2014
• Actual Primary Completion Date: July 31, 2018
• Actual Study Completion Date: July 24, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Botulinum toxin (BoNT); OnabotulinumtoxinA 100 Units diluted in 4cc saline, one time intramuscular administration	Drug: Botulinum toxin (BoNT); OnabotulinumtoxinA 100 Units diluted in 4cc saline, one time intramuscular administration
Placebo Comparator: Placebo; Saline, 4cc, one time intramuscular administration	Drug: Placebo; Saline, 4cc, one time intramuscular administration

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Improvement in Pain [ Time Frame: 1 month ]
   Self reported improvement in pain symptoms - a binary measurement of improvement/no improvement

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

• INCLUSION CRITERIA:
• Female gender
• Age between 18 and 55
• History of endometriosis at surgery
• Persistent pelvic pain for at least 3 months
• Pelvic floor spasm
• Negative pregnancy test (in women who have not had a hysterectomy)
• Willing to use reliable method of contraception for the month after botulinum toxin injection including oral contraceptives, IUD, and barrier with spermicide.
• Willing and able to give informed consent
• Willing and able to comply with study requirements

EXCLUSION CRITERIA:

• Women with other causes of chronic pelvic pain including infectious, gastrointestinal, psychological disorders, fibromyalgia and chronic fatigue syndrome based on review of medical history within 1 year of first study visit,
• Untreated severe cervical dysplasia or other gynecologic condition clinically significant abnormalities on physical or laboratory examinations that require evaluation or treatment or that would make participation unsafe
• Hysterectomy and bilateral salpingo-oophorectomy
• Pregnancy
• Lactation
• Allergy to albumen or botulinum toxin
• Presence of antibodies to botulinum toxin or loss of response to previous injections for any indication
• A known neuromuscular junction disorder such as myasthenia gravis or Eaton-Lambert syndrome
• History of urinary or fecal incontinence

• Known pelvic prolapse

  • Eligibility will be based on a physical exam at NIH at the first study visit, as well as history and available medical records within 1 year before the study visit. Negative test results will be documented to confirm study eligibility. If the Pap and the GC and chlamydia tests were not done outside of the NIH within the previous year, or if documentation of the negative test results is not available, we will await the results of the screening tests done at the NIH before administering the study medication.

Contacts and Locations

Locations

United States, Maryland

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, United States, 20892

Sponsors and Collaborators

National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

• Principal Investigator: Barbara I Karp, M.D.; National Institute of Neurological Disorders and Stroke (NINDS)

  Study Documents (Full-Text)

Documents provided by National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) ):

Study Protocol and Statistical Analysis Plan  [PDF] July 22, 2019

More Information

Additional Information:

NIH Clinical Center Detailed Web Page 

Publications:

Abbott JA, Jarvis SK, Lyons SD, Thomson A, Vancaille TG. Botulinum toxin type A for chronic pain and pelvic floor spasm in women: a randomized controlled trial. Obstet Gynecol. 2006 Oct;108(4):915-23. doi: 10.1097/01.AOG.0000237100.29870.cc.

Bhidayasiri R, Truong DD. Expanding use of botulinum toxin. J Neurol Sci. 2005 Aug 15;235(1-2):1-9. doi: 10.1016/j.jns.2005.04.017.

Jankovic J. Botulinum toxin in clinical practice. J Neurol Neurosurg Psychiatry. 2004 Jul;75(7):951-7. doi: 10.1136/jnnp.2003.034702.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Phan VT, Stratton P, Tandon HK, Sinaii N, Aredo JV, Karp BI, Merideth MA, Shah JP. Widespread myofascial dysfunction and sensitisation in women with endometriosis-associated chronic pelvic pain: A cross-sectional study. Eur J Pain. 2021 Apr;25(4):831-840. doi: 10.1002/ejp.1713. Epub 2021 Jan 8.

Tandon HK, Stratton P, Sinaii N, Shah J, Karp BI. Botulinum toxin for chronic pelvic pain in women with endometriosis: a cohort study of a pain-focused treatment. Reg Anesth Pain Med. 2019 Jul 8:rapm-2019-100529. doi: 10.1136/rapm-2019-100529. Online ahead of print.

• Responsible Party: National Institute of Neurological Disorders and Stroke (NINDS)
• ClinicalTrials.gov Identifier: NCT01553201
• Other Study ID Numbers: 120083; 12-N-0083
• First Posted: March 14, 2012
• Results First Posted: July 8, 2020
• Last Update Posted: July 28, 2020
• Last Verified: September 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) ):

Quality of Life; Endometriosis; Botulinum Toxin A; Pelvic Floor Muscle Spasm; Chronic Pelvic Pain

Additional relevant MeSH terms:

Muscle Cramp; Spasm; Hyperkinesis; Endometriosis; Pelvic Pain; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Pain; Neurologic Manifestations; Neuromuscular Manifestations; Nervous System Diseases; Muscular Diseases; Musculoskeletal Diseases; Dyskinesias; Botulinum Toxins; Acetylcholine Release Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Neurotransmitter Agents; Physiological Effects of Drugs