Recruiting
Phase 3

MI-Opioid Taper & Tizanidine

Sponsor:

Stanford University

Code:

NCT06027099

Conditions

Chronic Pain

Back Pain

Neck Pain

Opioid Misuse

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

Tizanidine

MI-Opioid Taper

Placebo

Enhanced Usual Care

Study Details

Brief summary:

The goal of this clinical trial is to learn whether a combined behavioral and pharmacologic intervention can help reduce opioid use, improve pain recovery, and prevent opioid misuse after surgery in adults undergoing elective surgery. The study includes adults aged 18 to 75 who have a history of long-term opioid use, defined as having access to opioids for 60 or more days within the 180 days before surgery.

The main questions it aims to answer are:

  • Does Motivational Interviewing with guided opioid tapering plus tizanidine (MI-Opioid Taper + Tizanidine) help participants return to their preoperative opioid use level or stop opioids faster than Enhanced Usual Care (EUC)?
  • Does the intervention reduce the time to pain resolution and decrease the likelihood of opioid misuse after surgery compared to EUC?

Researchers will compare MI-Opioid Taper + Tizanidine to MI-Opioid Taper with placebo and to EUC to see whether the intervention improves postoperative opioid and pain outcomes.

Participants will:

  • Complete a phone assessment and baseline survey before surgery
  • Be randomly assigned 7-13 days after surgery to one of three groups:

  • MI-Opioid Taper + tizanidine (MTT)
  • MI-Opioid Taper + placebo (MTP)
  • Enhanced Usual Care (EUC)
  • Complete brief weekly phone or video visits with a study clinician for 6 weeks starting 14 days after surgery
  • Take a study medication (tizanidine or placebo) three times daily for 5 weeks (MTT and MTP groups only)
  • Complete weekly online surveys for 6 months, followed by monthly surveys until 12 months after surgery to track pain, opioid use, and related outcomes

Conditions

Chronic Pain

Back Pain

Neck Pain

Opioid Misuse

Study ID

NCT06027099

Start date

Dec 5, 2024

Status verified date

May, 2026

Completion date

Jul, 2028

Anticipated

Primary completion date

Jan, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

INCLUSION CRITERIA:

  • 18 to 75 years of age
  • Able to speak, write, and read fluently in English
  • Scheduled for elective surgery at

  • Stanford University Medical Center,
  • Brigham and Women's Hospital (Harvard University),
  • Atrium Health Wake Forest Baptist Medical Center (Wake Forest University), or
  • University of Kansas Medical Center
  • Preoperative long-term opioid use (Defined as ≥ 60-day supply of opioids in the 180-day period prior to surgery), identified via self-report, state Prescription Drug Monitoring Program (PDMP), or Electronic Medical Records (EHR). Days may be nonconsecutive, and actual use of opioid supply is not required.
  • Willing and able to complete online assessments and study calls independently
  • On the preoperative Baseline assessments, least one of the following:

  • Current Opioid Misuse Measure (COMM-17): score ≥ 9
  • Tobacco, Alcohol, Prescription medication, and other Substance use (TAPS-1): Reported use more frequent than "Never" on any item except Tobacco; for Tobacco, "Yes" to at least one item on the TAPS-2 for Tobacco
  • Alcohol Use Disorders Identification Test (AUDIT-C): score ≥4 (men), ≥3 (women)
  • Modified Brief Pain Inventory (mBPI): "Yes" to at least one of the following:

  • Over the past 24 hours have you needed to take your pain medication to help you sleep?
  • Have you taken any pain medications for any reason other than your pain, such as to reduce anxiety or improve mood?
  • Have you taken more pain medication than was prescribed to you in the past 24 hours?
  • At the Post-Operative Call (7-13 days post-op): Postoperative daily opioid dose ≥ preoperative daily opioid dose (identified during the Pre-Surgery Call 5-1 day before surgery), measured in Morphine Milligram Equivalents (MME).

EXCLUSION CRITERIA

  • Infection, tumor, or fracture at the operative site
  • Allergy or intolerance to tizanidine
  • Current use of tizanidine
  • Renal impairment (Creatinine Clearance \[CrCl\] < 25 ml/min)
  • Hepatic impairment, including cirrhosis or elevated liver enzymes
  • Concurrent use of other α2-adrenergic agonists, skeletal muscle relaxants
  • Concurrent use of: fluvoxamine, ciprofloxacin,zileuton, fluoroquinolones, antiarrhythmics (amiodarone, mexiletine, propafenone, verapamil), cimetidine, famotidine, oral contraceptive pills, acyclovir, ticlopidine, and fexinidazole
  • Pre-existing hypotension, sedation, dizziness, severe respiratory insufficiency.
  • Opioid Use Disorder
  • Suicidality as assessed by the Patient Health Questionnaire-9 (PHQ-9) Question 9 score ≥ 1
  • Pregnancy, breastfeeding, or planning to conceive
  • Planned cancer treatment in the < 3 months following surgery
  • Conditions causing inability to complete assessments (education, cognitive ability, mental status, medical status)
  • Participating in another clinical trial with an active treatment arm

Study Design

Enrollment

375 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: MI-Opioid Taper and tizanidine

experimental: MI-Opioid Taper and placebo

active comparator: Enhanced Usual Care

Interventions

Tizanidine

Tizanidine 2mg three times a day for 5 weeks after surgery

MI-Opioid Taper

Motivational Interviewing (MI) and guided Opioid Tapering support adapting MI principles for enhancing motivation to change in pain treatment and tailoring key MI tools to postoperative opioid use delivered through weekly phone calls from weeks 2 to 7, and at week 11. The guided opioid tapering protocol will be a 25% total daily opioid dose reduction every 7 days with opioid discontinuation 7 days after reaching 1 opioid pill per day.

Placebo

1 tablet three times a day for 5 weeks after surgery

Enhanced Usual Care

Participants will receive weekly phone calls from weeks 2 to 7, and at week 11. 1 topic per call will be reviewed in this sequence:1) standardized instructions on taking opioid medications after surgery, 2) safe opioid use, 3) avoiding medication errors, 4) local mental health resources and 988 Suicide \& Crisis lifeline, 5) disposal of unused medications, 6) prescription drug abuse, and 7) complementary health approaches for chronic pain. Education materials will be reviewed in a didactic style without a tailored discussion.

Primary outcome measure

  • Time to Baseline Opioid Use [ Time Frame: From Postoperative Day 7 through Postoperative Day 365 ]

Central Contacts and Locations

Central contacts

Shana C Levine, BA, CARES RESEARCH COORDINATOR

650-649-9618Shana8@stanford.edu

SPARKLE (Strategies for Pain Alleviation though Research and Knowledge for Long-term Efficacy) Lab

CARESStudy@Stanford.edu

Locations

Stanford University Medical Center

Recruiting

Stanford, California, United States, 94305

Contacts

Jennifer M Hah, MD, MS

650-724-3193jhah@stanford.edu

Shana C Levine, BA

650-649-9618shana8@stanford.edu

Principal Investigator:

Jennifer M Hah, MD, MS

University of Kansas Medical Center

Recruiting

Kansas City, Kansas, United States, 66103

Contacts

Andrea Chadwick, MD, MSc, FASA

913-588-3479anicol@kumc.edu

FACE (Fibromyalgia And Centralized pain Exploration) Lab

913-588-7630facelab@kumc.edu

Principal Investigator:

Andrea Chadwick, MD

Harvard University- Brigham and Women's Hospital

Recruiting

Boston, Massachusetts, United States, 02115

Contacts

Samantha Meints, PhD (PRINCIPAL INVESTIGATOR)

612-205-0186smeints@bwh.harvard.edu

Caroline Allen, BS

617-732-9014callen22@bwh.harvard.edu

Principal Investigator:

Samantha Meints, PhD

Atrium Health Wake Forest Baptist Medical Center

Recruiting

Winston-Salem, North Carolina, United States, 27157

Contacts

Robert Hurley, MD, PhD, FASA

336-716-1228Robert.Hurley@Advocatehealth.org

Lynnette Harris, RN, BSN

336-716-8791Lynnette.Harris@advocatehealth.org

Principal Investigator:

Robert Hurley, MD, PhD, FASA

More Information

Sponsor

Stanford University

Last update posted

May 6, 2026

Last verified

May, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Stanford University on 2026-05-06.