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
  Purpose

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.

Condition Intervention Phase
Fibromyalgia Syndrome
Drug: mirtazapine
Drug: placebo
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Mahidol University:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 80
Study Start Date: December 2008
Study Completion Date: December 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: placebo
placebo
Drug: placebo
placebo
Other Name: placebo
Placebo Comparator: mirtazapine 15
mirtazapine 15 mg
Drug: mirtazapine
mirtazapine 15 mg or 30 mg tablet daily at bedtime for 13 weeks
Other Name: Remeron
Placebo Comparator: mirtazapine 30
mirtazapine 30mg
Drug: mirtazapine
mirtazapine 15 mg or 30 mg tablet daily at bedtime for 13 weeks
Other Name: Remeron

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00919295

Locations
Thailand
Siriraj Hospital, Mahidol University
Bangkoknoi, Bangkok, Thailand, 10700
Sponsors and Collaborators
Mahidol University
University of Texas
University of Wuerzburg
Investigators
Principal Investigator: Suwimon Yeephu Faculty of Pharmacy Mahidol University
Principal Investigator: Saithip Suttiruksa, Master Faculty of Pharmacy, Mahidol University
  More Information

No publications provided

Responsible Party: Suwimon Yeephu, Faculty of Pharmacy, Mahidol University
ClinicalTrials.gov Identifier: NCT00919295     History of Changes
Other Study ID Numbers: 323/2551(EC4)
Study First Received: June 11, 2009
Last Updated: July 24, 2012
Health Authority: Thailand: Ethical Committee

Keywords provided by Mahidol University:
Fibromyalgia syndrome
mirtazapine
randomized controlled trial
pilot study

Additional relevant MeSH terms:
Fibromyalgia
Myofascial Pain Syndromes
Syndrome
Disease
Muscular Diseases
Musculoskeletal Diseases
Nervous System Diseases
Neuromuscular Diseases
Pathologic Processes
Rheumatic Diseases
Mianserin
Mirtazapine
Adrenergic Agents
Adrenergic alpha-Antagonists
Adrenergic Antagonists
Antidepressive Agents
Antidepressive Agents, Second-Generation
Antidepressive Agents, Tricyclic
Central Nervous System Agents
Histamine Agents
Histamine Antagonists
Histamine H1 Antagonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Agents
Serotonin Antagonists
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014