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

Fibromyalgia Syndrome Clinical Trial

Official title:

Study of Anti-nociceptive Biogenic Amine Status, Indoleamine 2,3-dioxygenase Activity, Serum Levels of Cytokines, BDNF, BH4 and Mirtazapine Efficacy in Thai Fibromyalgia Syndrome Patients.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00919295
• Other study ID #: 323/2551(EC4)
• Status: Completed
• Phase: Phase 2
• First received: June 11, 2009
• Last updated: July 24, 2012
• Start date: December 2008
• Est. completion date: December 2011

Study information

• Verified date: July 2012
• Source: Mahidol University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Thailand: Ethical Committee
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: December 2011
• Est. primary completion date: October 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria for randomized controlled trial:

• 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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fibromyalgia
• Fibromyalgia Syndrome
• Myofascial Pain Syndromes
• Syndrome

Intervention

Drug:
• mirtazapine
mirtazapine 15 mg or 30 mg tablet daily at bedtime for 13 weeks
• placebo
placebo

Locations

Country	Name	City	State
Thailand	Siriraj Hospital, Mahidol University	Bangkoknoi	Bangkok

Sponsors (3)

Lead Sponsor	Collaborator
Mahidol University	University of Texas, University of Wuerzburg

Country where clinical trial is conducted

Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary outcome measure for part II of this study will be "change from baseline in the severity of the pain visual analog scale (PVAS) score" and pain responders (>= 30% PVAS reduction).		day 7, 21, 35, 63, 91 (day 0 = first day of starting expected dose)	No
Secondary	Depression, sleep quality, patient global assessment of disease status, FIQ, PGIC, quality of life, adverse events		day 7, 21, 35, 63, 91 (day 0 = the day of starting expected dose)	Yes