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

N/ANot Yet RecruitingNCT07382921

Beijing Tiantan Hospital164 enrolled

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

164

Conditions

Fibromyalgia Pregabalin Pain

Interventions

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.

Pregabalin with tizanidineDRUG

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).

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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)

Time frame: baseline , 12 weeks

Secondary Outcomes

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.

Time frame: 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.