Study of Indoleamine 2,3-dioxygenase Activity, Serum Levels of Cytokines, BDNF, BH4 and Mirtazapine Efficacy in Fibromyalgia Syndrome

NCT ID: NCT00919295

Last Updated: 2012-07-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-12-31
• Study Completion Date: 2011-12-31

Brief Summary

This study aims to investigate the anti-nociceptive biogenic amine (serotonin [5-hydroxytryptamine; 5-HT], norepinephrine [NE], dopamine [DA], and their metabolites) status, and serum levels of cytokines, BDNF and BH4 in Thai fibromyalgia syndrome (FMS) patients compared with a representative Thai population. The efficacy and the tolerability of mirtazapine as monotherapy for FMS will also be assessed. In addition, proof of concept of the indoleamine 2,3-dioxygenase (IDO) activity in FMS will be conducted.

The study will be divided into three parts. In part I, FMS patients of Thai ethnicity will be examined to determine the blood and/or urinary level of anti-nociceptive biogenic amines, cytokines, BDNF and BH4 by comparison with the demographically matched, but unrelated, healthy normal controls (HNC). In part II, the FMS subjects from part I study will be randomized to blinded therapy with mirtazapine or identical appearing placebo. There will be three treatment groups (N=1:1:1) to accommodate two dosages of mirtazapine (15 mg, 30mg) and placebo given before bedtime. Pill counts at baseline and at follow-up visits will document compliance. Standard outcome instruments (translated and validated in Thai language) will be used at baseline and at each of the follow-up visits. The co-primary outcome variable will be the changes in the pain visual analog scale (PVAS) score and pain responders (>= 30% PVAS reduction). Secondary clinical outcome variables of interest will include depression, insomnia, anxiety, physical function, morning stiffness, patient global assessment of disease status, patient global impression of change, fibromyalgia impact questionnaire (FIQ, quality of life and adverse experience. The changes of biogenic amine and IGF-1 concentrations in blood and/or urine with the treatment will be examined as the secondary biochemical measures. In part III, the IDO activity of depressed FMS, non-depressed FMS and HNC will be compared. Moreover, the effect of mirtazapine treatment on the IDO activity in depressed and non-depressed FMS patients will be assessed.

Study hypothesis

1. Anti-nociceptive biogenic amine levels in Thai FMS patients are lower than in Thai healthy normal control.

2. Higher IDO activity could be observed in FMS patients.

3. Higher cytokines could be observed in FMS patients.

4. Higher BDNF could be observed in FMS patients.

5. Lower BH4 could be observed in FMS patients.

6. Mirtazapine is effective in FMS treatment.

Conditions

Fibromyalgia Syndrome

Keywords

Fibromyalgia syndrome; mirtazapine; randomized controlled trial; pilot study

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

placebo

placebo

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

placebo

mirtazapine 15

mirtazapine 15 mg

Group Type: PLACEBO_COMPARATOR

mirtazapine

Intervention Type: DRUG

mirtazapine 15 mg or 30 mg tablet daily at bedtime for 13 weeks

mirtazapine 30

mirtazapine 30mg

Group Type: PLACEBO_COMPARATOR

mirtazapine

Intervention Type: DRUG

mirtazapine 15 mg or 30 mg tablet daily at bedtime for 13 weeks

Interventions

mirtazapine

mirtazapine 15 mg or 30 mg tablet daily at bedtime for 13 weeks

Intervention Type: DRUG

placebo

placebo

Intervention Type: DRUG

Other Intervention Names

Remeron

Eligibility Criteria

Inclusion Criteria

• male or female outpatients > 18 years of age, descended from Thai parents
• meet criteria for FMS as defined by the American College of Rheumatology 1990
• have a score of > 4 on the pain visual analog scale (PVAS) score at screening

Exclusion Criteria

• any severe or unstable physical or psychiatric disorder
• inflammation or injury or trauma in the previous month
• substance abuse within the past year
• serious suicide risk
• pregnancy or breastfeeding
• subject has an allergic reactions to mirtazapine or any of its constituents or severe allergic reactions to multiple medications
• comorbid inflammatory rheumatic diseases
• Use of medications or herbal agents with CNS activity
• regular use of analgesics with the exception of acetaminophen up to 2 gram/day
• chronic use of sedatives/hypnotics
• unable to discontinue medications that may affect the study results (all antidepressants, mood stabilizers, antipsychotics, sleep aids such as hypnotics, tranquilizers, sedating antihistamine and benzodiazepines, all analgesics including anticonvulsants, muscle relaxants, stimulant medications such as dextroamphetamine and methylphenidate, any other medications taken by the subject for the treatment of fibromyalgia
• unable to attend the follow-up schedule of the study
• not agree with avoidance or stable maintenance of unconventionalor alternative therapies, such as Thai traditional massage

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Mahidol University

OTHER

Sponsor Role: lead

University of Texas

OTHER

Sponsor Role: collaborator

University of Wuerzburg

OTHER

Sponsor Role: collaborator

Responsible Party

Suwimon Yeephu

Faculty of Pharmacy

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Suwimon Yeephu

Role: PRINCIPAL_INVESTIGATOR

Faculty of Pharmacy Mahidol University

Saithip Suttiruksa, Master

Role: PRINCIPAL_INVESTIGATOR

Faculty of Pharmacy, Mahidol University

Locations

Siriraj Hospital, Mahidol University

Bangkoknoi, Bangkok, Thailand

Countries

Thailand

Other Identifiers

323/2551(EC4)

Identifier Type: -

Identifier Source: org_study_id