Please select the eligibility criteria that correspond to the clinical trial below.
Title: Phase II Role of Immune-pineal Axis in Fibromyalgia: Noradrenergic Modulation and Chronotherapeutic Aspects
Brief Summary: Fibromyalgia is a common condition in clinical medical practice, characterized by diffuse musculoskeletal pain. Sleep disorders, chronic fatigue, depression, intestinal disorders and headache are also commonly associated with the syndrome .

Although the etiology of this syndrome is not well defined yet, it means involve multiple mechanisms, including low levels of serotonin, increased substance P in cerebrospinal fluid and altered circadian variation in sympathetic - parasympathetic balance, consistent with changes in sympathetic hyperactivity at night .

The immune - pineal system, formed by the integration of the adrenergic and immune systems pineal gland, appears to be involved in the genesis of the dysfunctions found in fibromyalgia. Melatonin is secreted by the pineal gland and has promoter activity of sleep. Studies show that melatonin and its precursors , serotonin and tryptophan are reduced in patients with fibromyalgia.

The present study aims to evaluate the relationship of immune - pineal system in the process of fibromyalgia , since dysfunction of this axis appears to govern the cascading events that participate in the pathophysiological process of this disease.


Options:
A: Inclusion Criteria:

* Women aged greater than or equal (\>=) 18 years
* Fibromyalgia diagnosed at least one year before
* History of generalized pain and at least 16 positive tender points (1990 American College of Rheumatology \[ACR\] criteria)
* Body Mass Index (BMI) less than or equal to(=\<) 32
* Normal GH stimulation test (insulin)
* Stable (\>= 3 months unchanged) standard treatment with amitriptyline (10-50 milligram per day \[mg/day\]) plus selective serotonin reuptake inhibitor (10-40 mg/day) plus tramadol (25-400 mg/day)
* Active rehabilitation program during the previous year (at least 30 minutes/day)
* Fibromyalgia Impact Questionnaire (FIQ) score \>=75
* IGF-1 serum level =\< 150 nanogram/milliliter (ng/mL) otherwise =\< 2 SD of the local lab normality)
* Normal response to IGF-1 generation test
* Chronic Fatigue Symptoms (Multidimensional Assessment of Fatigue \[MAF\])
* Effective anti-conception
* Willingness to comply with the protocol
* Written Informed consent

Exclusion Criteria:

* Major psychiatric condition
* Rheumatic disease, including systemic lupus erythematosus (SLE)
* Previous or current malignancies, active or inactive
* Clinical history intracranial space occupying lesion
* Reactive or secondary (rheumatoid arthritis \[RA\], osteoarthritis) fibromyalgia syndrome (FMS)
* Antinuclear antibody (ANA) greater than or equal 1:80
* Abnormal Creatine phosphokinase (CPK) or aldolase serum levels
* Not controlled thyroid disease in the last 3 months (free Thyroxine \[T4\] and Thyrotrophin-stimulating hormone \[TSH\] serum levels)
* Diabetes mellitus
* Adrenal gland disease (any abnormal cortisolemia, will be confirmed by 24-hour cortisoluria)
* Pregnancy or breast feeding
* Known to be hypersensitive to somatotropin or any of the excipients
B: Inclusion Criteria:

* patients diagnosed of fibromyalgia according to the American College of Rheumatology criteria
* written, informed consent
* able to understand and comply with the requirements of the study

Exclusion Criteria:

* pregnancy or breastfeeding
* unwillingness to discontinue other prescribed medications before entering in the study
* patients who had previously received trazodone without improvement or who did not tolerate the drug
* patients who had previously received pregabalin without improvement or who did not tolerate the drug (only for the phase II of the study)
C: Inclusion Criteria:

* ACR criteria for fibromyalgia
* A score of more or equal to 40 mm on the Pain Visual Analog Scale (VAS) and a an average score more or equal to 4 on 4 daily pain diaries

Exclusion Criteria:

* Patients with other severe pain conditions
* Patients with severe depression
* Patients taking excluded medications
D: Inclusion Criteria:

* Women 18-65 years old
* Fibromyalgia according to the criteria of the American College of Rheumatology (Wolfe 2010)
* Sign the informed consent
* Patients can take medication for chronic pain ( antidepressants , antiepileptics, for example), since there are at least two months

Exclusion criteria:

* patients who did not understand the Portuguese
* diagnosis of malignancies, severe psychiatric disorders , sleep disorders not related to fibromyalgia (apnea , sleepwalking , restless leg syndrome), Alzheimer's disease or any disease (rheumatologic, neurological, etc.) that can modify the evaluations or outcomes
* alcohol abuse or drug addiction
* patients who are performing acupuncture
* BMI greater than 35 ( BMI = body mass index) .
* Patients with history of allergy to amitriptyline or/and melatonin or any other contraindication for the use of these drugs

Answer: D