Rectal Versus Oral Diazepam Administration in the Treatment of Levator Ani Syndrome

Rectal Versus Oral Diazepam Administration in the Treatment of Levator Ani Syndrome in Participants Who Have Not Responded to Physical Therapy Treatment: A Prospective Randomized Study

This research involves collecting data about levator ani syndrome (LAS) associated rectal pain and a comparison of diazepam treatment administration routes. The goal of this research is to see if an alternative route of diazepam administration provides sufficient control of LAS discomfort and low sleep quality while minimizing systemic effects of diazepam (drowsiness).

Study Overview

• Status: Withdrawn
• Conditions: Levator Ani Syndrome
• Intervention / Treatment: Drug: Diazepam Tablets

Detailed Description

Levator ani syndrome (LAS) is described as a dull, aching pain of a patient's pelvic floor musculature. There is no known cause for the syndrome, yet pelvic floor muscle spasm and increased anal resting pressures have been hypothesized to result in the syndrome. LAS is commonly seen in patients with constipation, specifically outlet dysfunction constipation. Treatment for the syndrome involves a combination of bowel management, medications, and pelvic floor physical therapy (PT). Pelvic floor PT uses a variety of methods to help patients with LAS, including biofeedback and massage. The literature and the investigators experience shows that these pelvic floor PT approaches do not resolve all LAS symptoms.

Diazepam (Valium®) is used to treat levator ani syndrome in conjunction with other treatments to help relax the pelvic floor muscle group (levator ani). Diazepam has U.S. Food and Drug Administration (FDA) approval for use as a muscle relaxant. Investigators at Swedish Colon & Rectal Clinic are using diazepam intervention as a means for patients to gain relief from pain.

The work proposed aims to provide the first prospective, randomized, comparative study of the efficacy between administering diazepam rectally and administering the medication orally after pelvic floor PT treatment. Currently, other ways of administering diazepam have not been studied in the setting of the LAS condition. The Investigators performed a retrospective chart review last year and found some promising results for the efficacy of rectal and oral routes of diazepam for LAS. The Investigators want to determine if the route of administering diazepam as an adjunct to pelvic floor PT influences rectal pain relief for LAS patients.

Primary Objective: Compare the pain scores of participants with LAS after administering diazepam rectally or orally following six weeks of physical therapy.

Secondary Objectives:

1. Measure and compare the drowsiness levels of participants using rectal diazepam or oral diazepam. 2. Measure and compare the sleep quality of participants using rectal diazepam or oral diazepam.

All participants with the LAS diagnosis will initially receive 6 weeks of pelvic floor PT. After these six weeks, participants without effective pain relief will be randomized to one of two arms: rectal or oral diazepam administration. Participants will be dispensed 30 10 mg diazepam tablets to take daily (oral or rectal) for 4 weeks. Participants will be asked to complete 3 electronic questionnaires (VAS pain scale, Likert drowsiness scale, and Pittsburg Sleep Quality Index) each week while on the 10 week trial. Investigators plan to enroll 100 participants over approximately 5 years.

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Cecilia A Lynn, ARNP; Phone Number: 206-386-6600; Email: cecilia.lynn@swedish.org

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish Medical Center Colon Rectal Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients with a diagnosis of LAS according to the Rome IV criteria with:

   1. Chronic or recurrent rectal pain or aching
   2. Episodes lasting 30 minutes or longer
   3. Tenderness during traction on the puborectalis
   4. Exclusion of other causes of rectal pain
2. Patients who agree to undergo pelvic floor PT for six weeks prior to starting the medication treatment.
3. Women ≥ 18 years of age. Women of childbearing potential must undergo urine pregnancy testing prior to using the treatment medication.
4. Men ≥ 18 years of age.

Exclusion Criteria:

1. Participants who have had pelvic floor surgery or with recent conditions in which rectal suppositories are contraindicated.
2. Non-English speaking participants.
3. Women who are pregnant or breastfeeding.
4. Participants who are cognitively impaired, illiterate, or have a condition in which they are unable to consent for themselves.
5. Prisoners.
6. Participants allergic to benzodiazepines or have a sensitivity/intolerance to benzodiazepines.
7. Participants to which benzodiazepines are contraindicated or are on medications that interact with benzodiazepines.
8. Participants with current or history of Diagnostic and Statistical Manual of Mental Disorders (DSM-V) substance use disorder or Participants with a history of evidence of severe illness or any other conditions that would affect absorption or make the patient unsuitable for the study in the opinion of the investigator.
9. Participants already receiving medications in the benzodiazepine class within 2 weeks of screening visit for any reasons will be excluded based on increased risk for medication tolerance.
10. Participants who have undergone pelvic floor PT within 2 weeks of screening visit.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Oral Administration; 10 mg diazepam tablets to be taken orally once daily for 4 weeks.	Drug: Diazepam Tablets; Participants will be randomly assigned to either an oral or rectal administration of once daily 10 mg diazepam tablets for four weeks.
Active Comparator: Rectal Administration; 10 mg diazepam tablets to be taken rectally once daily for 4 weeks.	Drug: Diazepam Tablets; Participants will be randomly assigned to either an oral or rectal administration of once daily 10 mg diazepam tablets for four weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effectiveness of rectal administration versus oral administration in LAS pain management: Visual Analog Scale (VAS)	Participants will complete weekly electronic Visual Analog Scale (VAS) for pain for 6 weeks while on Physical Therapy only, followed by 4 weeks while taking diazepam (orally or rectally). Participants will be asked to select a number on a scale of 1 to 10, where 1 equals no pain and 10 equals worst pain.	10 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participant drowsiness while taking diazepam rectally versus orally	Participants will complete weekly electronic Likert drowsiness scale for 6 weeks while on Physical Therapy only, followed by 4 weeks while taking diazepam (orally or rectally). Participants will be asked to select a number on a scale of 1 to 5, where 1 equals much less drowsiness than usual and 10 equals much more drowsiness than usual.	10 weeks
Participant sleep quality while taking diazepam rectally versus orally: Pittsburg Sleep Quality Index	Participants will complete weekly electronic Pittsburg Sleep Quality Index for 6 weeks while on Physical Therapy only, followed by 4 weeks while taking diazepam (orally or rectally). The Pittsburg Sleep Quality Index measures overall sleep quality, evaluating seven categories of sleep: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The seven individual categories are weighted on a 0-3 interval scale. The global Pittsburg Sleep Quality Index score is then calculated by adding the seven individual category scores, which then provides a total score ranging from 0 to 21, where lower scores represent a healthier sleep quality.	10 weeks
Study Medication Adherence	Participants will be instructed to take diazepam (orally or rectally) daily for 4 weeks. Participants will bring in their pill bottles so that the study staff can manually count their pills to check for adherence.	4 weeks

Collaborators and Investigators

• Sponsor: Swedish Medical Center
• Investigators: Principal Investigator: Cecilia A Lynn, Swedish Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): January 9, 2020
• Primary Completion (Actual): February 21, 2023
• Study Completion (Actual): February 21, 2023

Study Registration Dates

• First Submitted: December 23, 2019
• First Submitted That Met QC Criteria: January 2, 2020
• First Posted (Actual): January 3, 2020

Study Record Updates

• Last Update Posted (Actual): April 19, 2023
• Last Update Submitted That Met QC Criteria: April 17, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Metabolic Diseases; Neurologic Manifestations; Disease; Gastrointestinal Diseases; Genetic Diseases, Inborn; Intestinal Diseases; Rectal Diseases; Metabolism, Inborn Errors; Hyperbilirubinemia, Hereditary; Syndrome; Pain; Anus Diseases; Crigler-Najjar Syndrome; 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; Diazepam
• Other Study ID Numbers: STUDY2019000291

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No