Baclofen/Diazepam Supps for Treatment of Pelvic Floor Myalgia (BDS)

A Randomized Double Blind Placebo Controlled Cross-over Trial of Baclofen and Diazepam Suppositories for the Management of Pelvic Floor Myalgia

This study is a randomized, placebo controlled double blind cross over trial. Patients presenting with pelvic floor myalgia will be asked to complete a series of standardized questionnaires to assess their pain, quality of life and sexual function and satisfaction. They will be randomized to either a treatment group or placebo group and will use the supplied suppositories once daily for 2 months. They will then undergo a one month "washout" after which they will be placed in the cross over group for a second two months of treatment.

Primary outcome measure: change in Visual Analogue Scale for Pain (VAS-P) scores before and after treatment Secondary outcome measures: change in Female Sexual Function Index (FSFI), Patient Global Impression of Improvement (PGI-I), and Short Form Health Survey (SF-12) before and after treatment

Study Overview

• Status: Unknown
• Conditions: Pelvic Floor Dyssynergia
• Intervention / Treatment: Drug: Baclofen/diazepam; Drug: Vaginal placebo

Detailed Description

Chronic pelvic pain is a complex multi-faceted problem that places a substantial burden on the healthcare resources. In Canada, the average hospital related cost for women requiring surgery or inpatient admission for chronic pelvic pain is $25 million each year. Chronic pelvic pain is defined as either persistent pain for at least 6 months or "recurrent episodes of abdominal/pelvic pain, hypersensitivity, or discomfort, often associated with elimination changes and sexual dysfunction in the absence of an organic etiology." Chronic pelvic pain is common and affects women of all ages and backgrounds. 15-20% of women have chronic pelvic pain lasting for more than 1 year.

Pelvic floor myalgia is an important and common contributor to chronic pelvic pain that may be present alone or may co-exist with other gynecological, urological, colorectal, and musculoskeletal medical conditions. The International Urogynecological Association/International Continence Society joint report published in February 2017 defines pelvic floor myalgia as pain in the musculature of the pelvic floor.6 Patients with high-tone pelvic floor dysfunction (HTPFD) have levator hypercontractility and present with pain with internal vaginal examination and intercourse. In a 2011 prospective cross-sectional study by Fitzgerald et al., 63% of patients with self-reported chronic pelvic pain examined by a physician and 73.7% of patients examined by a physiotherapist were found to have pelvic floor myalgia. Although pelvic floor myalgia is a common condition encountered in gynecology, it is frequently an unrecognized and under-treated component of chronic pelvic pain. Pelvic floor myalgia has a significant impact on the patient's quality of life. Persistent chronic pain may result in patient's anxiety, low mood, depression, sleep disturbances, feeling of hopelessness and helplessness, frustration, and psychological distress.

The first line of treatment for pelvic floor myalgia is pelvic floor muscle relaxation. Reducing the resting tone of pelvic floor musculature has been shown to improve chronic pelvic pain. Current treatment options for pelvic floor myalgia include pelvic floor physiotherapy, Thiele massage, biofeedback with electrical stimulation, behavioural modifications, acupuncture, medications such as antidepressants,1 trigger point injections with botulin A toxin, warm sitz baths, and neuromodulation.

Recently, intravaginal diazepam has been used an off-label treatment option for high-tone pelvic floor myalgia. Diazepam is a benzodiazepine derivative that has both antispasmotic and anxiolytic activity. It is used as a muscle relaxant and enhances the inhibitory action of gamma-amino butyric acid (GABA) on neuronal excitability, resulting in decreased action potentials. The benefit of local therapy is the avoidance of the common side effects of benzodiazepines such as drowsiness, fatigue, and ataxia. Currently, evidence is lacking in regards to the effectiveness of intravaginal diazepam on treatment of chronic pelvic pain. The 2010 retrospective chart review of 26 patients by Rogalski et al. revealed clinically significant reduction in Visual Analogue Scale for Pain (VAS-P) and Female Sexual Function Index (FSFI) with diazepam suppositories used for 30 days as an adjuvant therapy to pelvic floor physiotherapy and intramuscular trigger point injections. Similarly, the 2011 study revealed 62% improvement in symptoms with intravaginal diazepam.

Baclofen is a skeletal muscle relaxant. It is a GABA-B receptor agonist which is commonly used for treating spasticity. The literature on topical baclofen use in pelvic floor dysfunction is minimal. Topical therapy is advantageous to avoid the common systemic side effects such as drowsiness, hypotonia, hypotension, and headache. A retrospective study examining the use of topical baclofen for provoked vulvodynia showed an improvement in pain and sexual function.

Baclofen may also be used in combination with diazepam for treatment of pelvic floor myalgia. A 2016 retrospective chart review performed at the University of Saskatchewan revealed a reduction in both dyspareunia and pelvic floor muscle spasm with the use of baclofen and diazepam vaginal suppositories.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Patients with significant pelvic floor dyssynergia and pain during sexual activity.

Exclusion Criteria:

• Decide you do not wish to participate
• Are pregnant
• Have active pelvic inflammatory disease
• Have an active sexually transmitted infection (STI)
• Have a known or suspected cancer of the genital tract
• Have untreated or unevaluated changes in your Pap smear
• Are not currently sexually active
• Have an allergy to either baclofen or valium
• Are unable to complete the necessary study questionnaires

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Vaginal Baclofen/diazepam supp; Insert vaginal suppository once daily	Drug: Baclofen/diazepam; Vaginal suppository placed once daily, patients will record pelvic pain daily on a VAS scale, sexual satisfaction and quality of life on a standardized questionnaire weekly; Other Names: Lioresal
Placebo Comparator: Vaginal Placebo supp; Insert vaginal suppository once daily	Drug: Vaginal placebo; Vaginal suppository placed once daily, patient will record pelvic pain daily on a VAS scale, sexual satisfaction and quality of life on a standardized questionnaire weeky.; Other Names: suppository

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Visual Analogue Scale for Pain (VAS-P) scores before and after treatment	The scale ranges from 0 (no pain) to 10 (worst pain ever experienced)	5 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Female Sexual Function Index (FSFI)	Self report measure of female sexual dysfunction	5 months
Patient Global Impression of Improvement (PGI-I)	Ranks patients overall feeling about health from 1 (very much better) to 7 (very much worse)	5 months
Short form Health Survey (SF-12)	Standardized self assessment tool to measure overall health status	5 months

Collaborators and Investigators

• Sponsor: Dr. John A. Thiel Medical Professional Corporation

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2018
• Primary Completion (Anticipated): December 31, 2018
• Study Completion (Anticipated): December 31, 2018

Study Registration Dates

• First Submitted: January 26, 2018
• First Submitted That Met QC Criteria: February 2, 2018
• First Posted (Actual): February 9, 2018

Study Record Updates

• Last Update Posted (Actual): June 7, 2018
• Last Update Submitted That Met QC Criteria: June 5, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Pain; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Musculoskeletal Pain; Dyskinesias; Sexual Dysfunctions, Psychological; Sexual Dysfunction, Physiological; Vaginal Diseases; Myalgia; Ataxia; Vaginismus; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Antiemetics; Gastrointestinal Agents; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Anticonvulsants; Neuromuscular Agents; Muscle Relaxants, Central; GABA Agonists; GABA-B Receptor Agonists; Diazepam; Baclofen
• Other Study ID Numbers: Jthiel

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: only pooled data will be shared outside of the research team

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No