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

Official title

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

Overview

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.

Interventions

• 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
• 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

Primary outcome measures

• Average pain intensity [Time frame: baseline , 12 weeks]

Secondary outcome measures (9)

• Fibromyalgia Impact Questionnaire Revised [Time frame: weekly(from baseline to 24 weeks)]
• Medical Outcome Study Short Form 36 Health Survey (SF-36) [Time frame: baseline , 4, 8, 12, 16, 20, and 24 weeks]
• The Patient's Global Assessment [Time frame: baseline , 4, 8, 12, 16, 20, and 24 weeks]
• The Beck II Depression Inventory [Time frame: baseline , 4, 8, 12, 16, 20, and 24 weeks]
• The Pittsburgh Sleep Quality Index [Time frame: baseline , 4, 8, 12, 16, 20, and 24 weeks]
• The Hospital Anxiety and Depression Scale [Time frame: baseline , 4, 8, 12, 16, 20, and 24 weeks]
• The Perceived Stress Scale [Time frame: baseline , 4, 8, 12, 16, 20, and 24 weeks]
• Pain distribution [Time frame: baseline , 4, 8, 12, 16, 20, and 24 weeks]
• Frequency and severity of AEs [Time frame: baseline , 4, 8, 12, 16, 20, and 24 weeks]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Beijing Tiantan Hospital, Capital Medical University in Beijing — Beijing

Publications

• Liu Q, Wen C, Dai Y, Ma T, Liu M, Jia Z, Luo F, Wang D. Efficacy and Safety of Pregabalin-Tizanidine vs Pregabalin in Patients with Fibromyalgia: Study Protocol for a Multicenter, Prospective, Randomized, Controlled, Open-Label, Blinded Endpoint Trial. J Pain Res. 2026 May 15;19:605429. doi: 10.2147/JPR.S605429. eCollection 2026. PMID 42170616

Identifiers

NCT: NCT07382921 · KY2025-217-03-08

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗