A Randomized Trial of Oral Iron Therapy in Fibromyalgia
Condition: Primary Fibromyalgia
MeSH terms: Fibromyalgia; Myofascial Pain Syndromes
Study type: Interventional
Phase: Phase 3

Summary: 
      Fibromyalgia (FM) is a disorder with chronic widespread musculoskeletal pain for which no
      alternative cause can be identified. The condition is often accompanied by other features
      such as fatigue, stiffness, cold intolerance, cognitive impairment, intolerance to external
      stimuli, sleep disturbances, anxiety and depression, which significantly affect the quality
      of life. Fibromyalgia is characterized by altered pain perception, and studies have shown
      fibromyalgia to be more prevalent in patients with iron deficiency anemia. Iron is essential
      for a number of enzymes involved in serotonin and dopamine synthesis. Deficiency of
      serotonergic neuronal functioning might be related to the pathophysiology of FM.

      This study attempts to explore the use of oral iron as a cheap and readily available
      alternative for the treatment of FM .
    

Detailed description: 
      Fibromyalgia (FM) is a disorder with chronic widespread musculoskeletal pain for which no
      alternative cause can be identified . The condition is often accompanied by other features
      such as fatigue, stiffness, cold intolerance, cognitive impairment, intolerance to external
      stimuli, sleep disturbances, anxiety and depression, which significantly affect the quality
      of life. Fibromyalgia is characterized by altered pain perception, and studies have shown
      fibromyalgia to be more prevalent in patients with iron deficiency anemia. Iron is essential
      for a number of enzymes involved in serotonin and dopamine synthesis. Deficiency of
      serotonergic neuronal functioning might be related to the pathophysiology of FM. A
      dysregulation of dopaminergic transmission in the pathophysiology of FM has also been
      suggested. This has brought forth the postulation that iron as a cofactor in serotonin and
      dopamine production may have a role in the etiology of FM.

      A number of therapies are currently in vogue for FM, both pharmacological and
      non-pharmacological. Drugs shown to be effective in FM include tricyclic
      antidepressants(amitryptiline, cyclobenzaprine), dual reuptake inhibitors (duloxetine,
      milnacipran) and alpha-2-delta ligands (pregabalin, gabapentin). However cost is a major
      factor, and often treatment results are disappointing . Hence the investigators planned to
      conduct a randomized controlled trial of iron therapy in fibromyalgia . IF proven, iron could
      be a cheap and easily available alternative for the treatment of this common and often
      disabling condition.

      Materials and methods:

      Patients with FM attending the OPD of the Department of Clinical Immunology will be
      identified . Diagnosis shall be made as per the ACR 2010 preliminary diagnostic criteria for
      fibromyalgia and measurement of symptom severity. After seeking informed consent, the
      subjects will undergo baseline investigation to look for Hb, thyroid function tests and
      25-OH-Vitamin. Patients with a Hb<8 g or having hypothyroidism , deficiency of Vitamin D or
      any connective tissue disease will be excluded from the study. Patients with a baseline FIQ
      >40 will be taken up for study. Baseline depression will be assessed using BPHQ and patients
      with a baseline BPHQ > 4 will be excluded from study. Following this, the patients will
      undergo assessment of serum ferritin at baseline, and irrespective of serum ferritin levels,
      will be randomized into 2 groups. Target sample size in each group will be 60. The groups
      will be blinded from both the patients and the investigators, and allocation concealment will
      be maintained by use of pre-sealed envelopes and drug packets. Group A will receive standard
      of care treatment for fibromyalgia (Amitryptiline up to 25 mg/day, Duloxetine upto 60 mg/day,
      Pregabalin upto 300 mg/day either singly or in combination) along with placebo for 3 months.
      Group B will receive standard of care treatment for fibromyalgia (Amitryptiline upto 25
      mg/day, Duloxetine upto 60 mg/day, Pregabalin up to 300 mg/day either singly or in
      combination) along with 230 mg of oral elemental iron daily for 3 months. Assessment at
      baseline and at 3 months will be done with respect to the primary end points - Widespread
      Pain Index (WPI), Symptom Severity Scale score (SSS), Hindi version of Fibromyalgia Impact
      Questionnaire (FIQ) , and secondary end points - Visual Analog Scale for pain (VAS) , Hindi
      version of Brief Physical Health Questionnaire (BPHQ) , Hindi version of SF-36 questionnaire.
      Patients will be monitored for side effects of oral iron therapy ( nausea,vomiting,
      gastrointestinal irritation , constipation , diarrhea) . At the end of 3 months, statistical
      analysis will be done to determine significance of difference between placebo groups A and B
      with respect to the above mentioned end points. Patients with a change in FIQ > 25% will be
      taken as responders. The change in levels of various end points before and after, viz. WPI,
      SSS, VAS, BPHQ, SF-36 will be a secondary consideration.

      Significance:

      This study attempts to explore the use of oral iron as a cheap and readily available
      alternative for the treatment of FM .
    

Intervention name(s): Oral Iron; Oral Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 230 mg of elemental oral iron tablets will be administered daily for 3 months; Oral tablets matching oral iron will be administered daily for 3 months
Other intervention name(s): Drug; Placebo
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Fibromyalgia