Efficacy and Safety of Pregabalin/Tizanidine vs. Pregabalin in Patients With Fibromyalgia

Efficacy and Safety of Pregabalin/Tizanidine vs. Pregabalin in Patients With Fibromyalgia: a Prospective, Randomized, Open-label, Blinded Endpoint (PROBE) Trial

Fibromyalgia (FM) is a chronic pain syndrome characterized by widespread pain, fatigue, and emotional disorders. Its onset is related to factors such as central sensitization and imbalance of neurotransmitters. The current mainstream treatments include pregabalin, but the efficacy of pregabalin is limited, with only 25%-40% pain relief rate, and adverse reactions are common.Tizanidine is an imidazoline derivative and a centrally acting alpha-2 receptor agonist with skeletal muscle relaxant, sedative and anxiolytic properties.we carried out an open-label clinical trial in order to evaluate the efficacy and safety of combined treatment with tizanidine and pregabalin for pain in FM.

Study Overview

• Status: Not yet recruiting
• Conditions: Pain; Fibromyalgia; Pregabalin
• Intervention / Treatment: Drug: Pregabalin; Drug: Pregabalin with tizanidine

• Study Type: Interventional
• Enrollment (Estimated): 164
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Fang Luo; Phone Number: 13611326978; Email: 13211326978@163.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China
      • Beijing Tiantan Hospital, Capital Medical University in Beijing
      • Contact: Fang Luo; Phone Number: (86) 010 59976664; Email: 13611326978@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1.Aged 18-65 years. 2.Fulfill the 2016 updated American College of Rheumatology (ACR) diagnostic criteria for fibromyalgia.

  3.Sufficient cognitive function, visual acuity and language skills to complete questionnaires and pain diaries and to participate in telephone communication with study nurses to permit titration of the study drugs.

  4.Experienced daily pain (≥4/10 on a numerical rating scale) for at least 3 months.

Exclusion Criteria:

• 1.Presence of a painful condition, including inflammatory rheumatic disease, more than 50% as severe as but distinct from fibromyalgia.

  2.Women who are pregnant or lactating. 3.Women of childbearing potential not using adequate contraceptives. 4.End-stage kidney or liver disease. 5.Unstable cardiovascular disease (myocardial infarction within the preceding year, unstable angina, or congestive heart failure) or clinically relevant abnormal 12-lead electrocardiogram.

  6.Any poorly controlled medical condition that, in the opinion of the investigator, would interfere with proper conduct of the trial.

  7.Severe depression, as determined by a Beck Depression Inventory-II score of 29 or more suicidal ideation, as determined by a Beck Depression Inventory-II item 9 score of 2 or more any current major psychiatric disorder (e.g., schizophrenia, bipolar disorder) that is not well controlled.

  8.Hypersensitivity to any of the study medications. 9.Any current alcohol or drug abuse or dependence (except nicotine and caffeine).

  10.Those taking more than 90 mg morphine equivalents per day.

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: Pregabalin monotherapy group	Drug: Pregabalin; The patients receive open-label pregabalin (Pfizer Pharmaceutical Co. Ltd, New York) titration therapy. In the first week, patients receive the starting dose of 150 mg/day (75 mg twice daily) escalated, based on efficacy and tolerability, at weekly visits to increase by 150 mg per week. A final dose of 450 mg/day (225 mg twice daily). However, during this flexible dose titration, the final dose arrived at during the maximal tolerated dose week (week 3 of the treatment period) could be lower than the ceiling dose of 450 mg, if the patient could not tolerate the dose increase, it is reduce to the pre-escalation dose. Thus, this trial will not use a forced titration to the ceiling dose of 450 mg/day.
Experimental: Pregabalin with tizanidine group	Drug: Pregabalin with tizanidine; All patients receive tizanidine in an open-label fashion. The tizanidine dose is slowly escalated over approximately 3 weeks. The initial dosage is 2 mg/d at bedtime. The dosage is increased by 2 mg every 2 days in the first week in 3 divided doses. The dosage is then increased more rapidly by 4 mg every 2 days in the second week divided 3 times a day. During the third week, the dose was further escalated by 6 mg every 2 days to a maximum of 24 mg/d divided 3 times a day. If a patient could not tolerate a particular current specific dosage increase because of side effects, he or she is maintain at the previous dosage during the trial period. The patients receive open-label pregabalin (Pfizer Pharmaceutical Co. Ltd, New York) titration therapy. In the first week, patients receive the starting dose of 150 mg/day (75 mg twice daily) escalated, based on efficacy and tolerability, at weekly visits to increase by 150 mg per week. A final dose of 450 mg/day (225 mg twice daily).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average pain intensity	The primary outcome is change from baseline to 12 weeks of treatment in average pain intensity during the last 7 days on an 11-point rating scale (ranging from 0 = "no pain" to 10 = "unbearable pain") using the first item from the symptom part of the Fibromyalgia Impact Questionnaire Revised (FIQR)	baseline , 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fibromyalgia Impact Questionnaire Revised	The FIQR is a well-validated multidimensional instrument that measures participant-rated overall severity of fibromyalgia, including intensity of pain, physical function, fatigue, morning tiredness, depression, anxiety, job difficulty, and overall well-being. Each item is standardized on a scale ranging from 0 to 10, with lower scores indicating more improvement or less negative impact. In addition, FIQR is also assessed weekly during the intervention period for all groups of participants as well as at the 24-week time points as secondary outcomes.	weekly(from baseline to 24 weeks)
Medical Outcome Study Short Form 36 Health Survey (SF-36)	Health Related Quality of Life assessments are made using the Medical Outcome Study Short Form 36 Health Survey (SF-36). The SF-36 is a self-administered, 36-item questionnaire that assesses the concepts of physical functioning, role limitations due to physical problems, social function, bodily pain, general mental health, role limitations due to emotional problems, vitality, and general health perceptions. Summary scores include physical function, mental function, and combined total function. Scores range from 0 to 100, with higher scores indicating better health status.	baseline , 4, 8, 12, 16, 20, and 24 weeks
The Patient's Global Assessment	The Patient's Global Assessment (Global Visual Analogue Scale) is a visual analogue scale that measures the level of fibromyalgia severity on a 10-point scale with 10 reflecting the most extreme severity and 0 reflecting no severity.	baseline , 4, 8, 12, 16, 20, and 24 weeks
The Beck II Depression Inventory	The Beck II Depression Inventory (BDI) is a 21-question, validated, self-report instrument that measures the severity of depressive symptoms (each scored 0-3, sum=0-63). Higher scores reflect a greater degree of symptom severity. The total questionnaire score ranges from 0 to 63 points. The result is interpreted by the usual classifications as follows: no depression (0-9 points), mild depression (10-18 points), moderate depression (19-29 points) and severe depression (>30 points).	baseline , 4, 8, 12, 16, 20, and 24 weeks
The Pittsburgh Sleep Quality Index	The Pittsburgh Sleep Quality Index is an 11-item, validated, self-report questionnaire that measures sleep quality. Lower scores are associated with better sleep quality. This questionnaire has 7 dimensions: subjective quality, sleep latency, sleep duration, habitual sleep efficacy, sleep perturbations, use of hypnotic medication, and daily dysfunction. Each dimension is scored from 0 (no problems) to 3 (severe problems), where the total score varies in a range from 0 to 21 points.	baseline , 4, 8, 12, 16, 20, and 24 weeks
The Hospital Anxiety and Depression Scale	The Hospital Anxiety and Depression Scale is a 14-item, validated, self-report questionnaire that assesses levels of depression and anxiety. Higher scores reflect greater levels of anxiety and depression.	baseline , 4, 8, 12, 16, 20, and 24 weeks
The Perceived Stress Scale	The Perceived Stress Scale is the most widely used psychological instrument for measuring the perception of stress. The 10-item scale also includes a number of direct queries about current levels of experienced stress. For this instrument, higher scores reflect a greater degree of symptom severity.	baseline , 4, 8, 12, 16, 20, and 24 weeks
Pain distribution	Pain distribution: assessed by the Widespread Pain Index (WPI) from the 2016 diagnostic criteria for fibromyalgia.	baseline , 4, 8, 12, 16, 20, and 24 weeks
Frequency and severity of AEs	Frequency and severity of AEs, Patient safety will be ensured by vigilant AE assessment and judicious drug titration. Any occurrences of major AEs will be tracked as secondary outcomes and also reported to the Ethics Board. Assessment and reporting of AEs will adhere to Consolidated Standards for Reporting Trials recommendations.	baseline , 4, 8, 12, 16, 20, and 24 weeks

Collaborators and Investigators

• Sponsor: Beijing Tiantan Hospital
• Collaborators: People's Hospital of Xinjiang Uygur Autonomous Region; Sichuan Provincial People's Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): January 30, 2026
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: January 26, 2026
• First Submitted That Met QC Criteria: January 26, 2026
• First Posted (Actual): February 3, 2026

Study Record Updates

• Last Update Posted (Actual): February 4, 2026
• Last Update Submitted That Met QC Criteria: February 2, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Neuromuscular Diseases; Rheumatic Diseases; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain; Fibromyalgia; Amino Acids, Peptides, and Proteins; Organic Chemicals; Acids, Acyclic; Carboxylic Acids; Amino Acids; gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Pregabalin; tizanidine
• Other Study ID Numbers: KY2025-217-03-08

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in this article, after de-identification (text, tables, figures and appendices) are available. Derived data supporting the findings of this study are available from the corresponding author Fang Luo on request.

Drug and device information, study documents

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