Gabapentin and Tizanidine for Insomnia in Chronic Pain

Effect of Gabapentin and Tizanidine on Insomnia in Chronic Pain Patients: A Randomized, Double-blind, Placebo-controlled Crossover Trial.

This is a double-blind, placebo-controlled, randomized, crossover trial aimed at assessing the effect of gabapentin and tizanidine, two pain medications, on insomnia in chronic pain patients.

Study Overview

• Status: Completed
• Conditions: Chronic Pain; Insomnia Due to Medical Condition
• Intervention / Treatment: Drug: Tizanidine; Drug: Gabapentin; Drug: Placebo

Detailed Description

Chronic pain and insomnia are highly prevalent conditions affecting 10-25% and 6-10% of the general population, respectively. Importantly, these two conditions frequently co-occur, with 50-80% of chronic pain patients reporting sleep disturbances. Identifying medication that alleviates pain and insomnia simultaneously may help reduce risks associated with polypharmacy, including drug-drug interactions.

In this double-blind, placebo-controlled, randomized, crossover trial, gabapentin and tizanidine, two drugs which are respectively commonly used to treat neuropathic and musculoskeletal pain, will be compared to each other and to placebo in their ability to alleviate insomnia in chronic pain patients.

In each week, patients will receive 3-night (Friday-Sunday) trials each of placebo, gabapentin or tizanidine in a randomized, double-blind order and will monitor their insomnia using the Athens Insomnia Scale (AIS) questionnaire (adapted to fit the time frame of this trial). The primary outcome consists of the difference in mean AIS scores between the 3 treatments at the primary time point, which is Monday of each week (after 3 nights of drug intake).

Patients will also monitor their sleepiness, pain relief and overall improvement as secondary variants using the Stanford Sleepiness Scale (SSS), Visual Analog Scale (VAS), and Patient's Global Impression of Change (PGIC) questionnaires respectively.

Scores on the Monday preceding the first treatment will serve as baseline and the period between treatments (i.e. Monday-Thursday nights) will serve as a 4-day washout period between treatments.

Our hypothesis is that gabapentin and tizanidine will both be more effective than placebo in alleviating insomnia in chronic pain patients but will not be different from one another.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92037
      • Center for Pain Medicine, UC San Diego

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• BMI ≤ 35
• Any ethnicity
• Must be able to communicate in English
• Must have access to email and be able to respond to REDCap questionnaires in English
• Has a chronic pain condition (≥ 3 months of pain)
• Reports sleep disturbance and scores ≥ 6 on AIS questionnaire
• Ability to provide informed consent

Exclusion Criteria:

• Pregnancy
• Breastfeeding
• Has diagnosis of chronic kidney disease
• Has known QT prolongation >500 msec on prior EKG
• Inability to complete daily questionnaires
• Allergy to, or intolerance of, any of tizanidine or gabapentin
• Shift workers
• Anticipated travel across multiple time zones (jetlag) during the duration of the trial
• Circadian misalignment
• Prior syncope experience and/or fear of blood/needles (if a blood draw is required)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tizanidine 2mg; Friday night: 1 capsule Saturday night: 2 capsules Sunday night: Subject chooses 1-2 capsules	Drug: Tizanidine; Friday night: 1 capsule of 2 mg, Saturday night: 2 capsule of 2 mg (total 4 mg), Sunday night: choice of 1 or 2 capsules of 2 mg (total of 2 or 4 mg); Other Names: Zanaflex
Experimental: Gabapentin 300mg; Friday night: 1 capsule Saturday night: 2 capsules Sunday night: Subject chooses 1-2 capsules	Drug: Gabapentin; Friday night: 1 capsule of 300 mg, Saturday night: 2 capsule of 300 mg (total 600 mg), Sunday night: choice of 1 or 2 capsule of 300 mg (total of 300 or 600 mg); Other Names: Neurontin
Placebo Comparator: Placebo; Friday night: 1 capsule Saturday night: 2 capsules Sunday night: Subject chooses 1-2 capsules	Drug: Placebo; Friday night: 1 capsule, Saturday night: 2 capsule, Sunday night: choice of 1 or 2 capsules; Other Names: Sham; Sugar Pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sleep quality	Comparison of group means for Athens Insomnia Scale scores between the 3 treatment groups placebo, gabapentin and tizanidine. Total Athens Insomnia Scale score ranges from 0 to 24. The higher the score, the more severe the insomnia symptoms experienced by the patient.	Monday after 3 nights of drug intake

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Intensity	Comparison of group means for Visual Analog Scale scores between the 3 treatment groups placebo, gabapentin and tizanidine. Visual Analog Scale score ranges from 0 to 10. The higher the score, the worse the pain experienced by the patient.	Monday after 3 nights of drug intake
Alertness	Comparison of group means for Stanford Sleepiness Scale scores between the 3 treatment groups placebo, gabapentin and tizanidine. Stanford Sleepiness Scale score ranges from 1 to 7. The higher the score, the more sleepy and less alert the patient.	Monday after 3 nights of drug intake
Overall improvement	Comparison of group means for Patient Global Impression of Change scores between the 3 treatment groups placebo, gabapentin and tizanidine. Patient Global Impression of Change score ranges from 1 to 7. The higher the score, the more improvement reported by the patient.	Monday after 3 nights of drug intake
Categorical assessment of insomnia improvement	Percentage of patients with a 30% improvement from baseline in individual Athens Insomnia Scale scores for each of the 3 treatments placebo, gabapentin and tizanidine. Total Athens Insomnia Scale score ranges from 0 to 24. The higher the scores, the more severe the insomnia symptoms experienced by the patient.	Monday after 3 nights of drug intake

Collaborators and Investigators

• Sponsor: University of California, San Diego
• Collaborators: National Center for Advancing Translational Sciences (NCATS)
• Investigators: Principal Investigator: Nathaniel Schuster, MD, UC San Diego

Study record dates

Study Major Dates

• Study Start (Actual): July 29, 2020
• Primary Completion (Actual): December 1, 2024
• Study Completion (Actual): December 1, 2024

Study Registration Dates

• First Submitted: May 22, 2020
• First Submitted That Met QC Criteria: June 10, 2020
• First Posted (Actual): June 12, 2020

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 1, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Chronic Pain; Insomnia; Gabapentin; Placebo; Tizanidine
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Sleep Wake Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Chronic Pain; Sleep Initiation and Maintenance Disorders; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Central Nervous System Depressants; Sensory System Agents; Analgesics; Neurotransmitter Agents; Anti-Anxiety Agents; Tranquilizing Agents; Psychotropic Drugs; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Anticonvulsants; Antimanic Agents; Excitatory Amino Acid Agents; Excitatory Amino Acid Antagonists; Neuromuscular Agents; Parasympatholytics; Muscle Relaxants, Central; Gabapentin; Tizanidine
• Other Study ID Numbers: 191167; UL1TR000100 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Deidentified data will be shared in a manner TBD based on funding availability and journal requirements.
• IPD Sharing Time Frame: Beginning 12 months and ending 3 years following article publication.
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal. Proposals should be sent to nmschuster@health.ucsd.edu.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

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.: Yes