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

This study has been completed.
Sponsor:
Collaborators:
University of Texas
University of Wuerzburg
Information provided by (Responsible Party):
Suwimon Yeephu, Mahidol University
ClinicalTrials.gov Identifier:
NCT00919295
First received: June 11, 2009
Last updated: July 24, 2012
Last verified: July 2012

June 11, 2009
July 24, 2012
December 2008
October 2011   (final data collection date for primary outcome measure)
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). [ Time Frame: day 7, 21, 35, 63, 91 (day 0 = first day of starting expected dose) ] [ Designated as safety issue: No ]
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". [ Time Frame: day 7, 21, 35, 63, 91 (day 0 = first day of starting expected dose) ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00919295 on ClinicalTrials.gov Archive Site
Depression, sleep quality, patient global assessment of disease status, FIQ, PGIC, quality of life, adverse events [ Time Frame: day 7, 21, 35, 63, 91 (day 0 = the day of starting expected dose) ] [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
Study of Indoleamine 2,3-dioxygenase Activity, Serum Levels of Cytokines, BDNF, BH4 and Mirtazapine Efficacy in Fibromyalgia Syndrome
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.

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.
Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
Fibromyalgia Syndrome
  • Drug: mirtazapine
    mirtazapine 15 mg or 30 mg tablet daily at bedtime for 13 weeks
    Other Name: Remeron
  • Drug: placebo
    placebo
    Other Name: placebo
  • Placebo Comparator: placebo
    placebo
    Intervention: Drug: placebo
  • Placebo Comparator: mirtazapine 15
    mirtazapine 15 mg
    Intervention: Drug: mirtazapine
  • Placebo Comparator: mirtazapine 30
    mirtazapine 30mg
    Intervention: Drug: mirtazapine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
80
December 2011
October 2011   (final data collection date for primary outcome measure)

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
Both
18 Years and older
Yes
Contact information is only displayed when the study is recruiting subjects
Thailand
 
NCT00919295
323/2551(EC4)
No
Suwimon Yeephu, Mahidol University
Mahidol University
  • University of Texas
  • University of Wuerzburg
Principal Investigator: Suwimon Yeephu Faculty of Pharmacy Mahidol University
Principal Investigator: Saithip Suttiruksa, Master Faculty of Pharmacy, Mahidol University
Mahidol University
July 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP