Growth Hormone in Neuroendocrine Dysfunction With Severe Fibromyalgia Syndrome

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the efficacy of recombinant human growth hormone (r-hGH) treatment in severe fibromyalgia subjects with growth axis dysfunction.

Official Title
-----------------
Growth Hormone Treatment of Severe Fibromyalgia Syndrome Associated With Functional Failure of Somatotropic Axis. A Multicentre, Randomized, Double-blind, Placebo-controlled Study.

Conditions
-----------------
Fibromyalgia

Intervention / Treatment
-----------------
* Drug: Saizen®
* Drug: Placebo and Saizen®


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Saizen®<br> | Drug: Saizen®<br>* Saizen® (Somatropin) 0.006 milligram per kilogram (mg/kg) will be administered subcutaneously daily for 12 months. Dose will be titrated (an increase of 0.2 milligram per day) if the increase in insulin-like growth factor 1 (IGF-1) is less than 50 percent of the baseline value. Dose titrations will be made at Month 1, 3, 7 and 9.<br>* Other names: Somatropin;|
| Active Comparator: Placebo + Saizen®<br> | Drug: Placebo and Saizen®<br>* Placebo matched to Saizen® will be administered for the first 6 months followed by treatment with Saizen® (Somatropin) 0.006 mg/kg subcutaneously daily for next 6 months. Saizen® dose will be titrated (an increase of 0.2 milligram per day) if the increase in insulin-like growth factor 1 (IGF-1) is less than 50 percent of the baseline value. Dose titrations will be made at Month 7 and 9.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Less Than 11 Tender Points at Month 6 | The musculoskeletal component in form of pain on palpation in at least 11 of 18 tender point sites is required to fulfill the American College of Rheumatology (ACR) criteria for fibromyalgia syndrome, An important response is considered when the number of tender points falls below 11 since it is the threshold for fibromyalgia diagnosis. | Month 6 | 
| Percentage of Participants With Less Than 11 Tender Points at Month 12 | The musculoskeletal component in form of pain on palpation in at least 11 of 18 tender point sites is required to fulfill the ACR criteria for fibromyalgia syndrome, An important response is considered when the number of tender points falls below 11 since it is the threshold for fibromyalgia diagnosis. | Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fibromyalgia Impact Questionnaire (FIQ) Total Score | Fibromyalgia Impact Questionnaire (FIQ) is a 10-item questionnaire that measures physical impairment, well-being, missed work, pain, fatigue, rest, stiffness, anxiety, and depression. Score ranges from 0 (best result - very well) to 100 (worst result - awful). | Baseline, Month 1, 3, 6, 7, 9 and 12 | 
| Visual Analog Scale (VAS) Total Score | Visual Analog Scale (VAS) is a 100 millimeter (mm) scale. Intensity of pain range: 0 mm=no pain to 100 mm=worst possible pain. | Baseline, Month 1, 3, 6, 7, 9 and 12 | 
| EuroQol 5-Dimensions (EQ-5D) Total Score | EuroQol 5-Dimensions (EQ-5D) questionnaire is a measure of health status and quality of life (QoL). The EQ-5D defines health in terms of mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Score range for each item is 0 to 3, with 3 being the most severe. Total score range is 0 to 15. Lower scores represent a better QoL. | Baseline, Month 1, 3, 6, 7, 9 and 12 | 
| Multidimensional Assessment of Fatigue (MAF) Total Score | Multidimensional Assessment of Fatigue (MAF) consists of 16 questions. The score range for first 14 questions is between 0 and 10 for each question while for the last two questions it is 0 and 4 for each question. Total score range for first 14 questions is 0 to 100 and for last two questions is 0 to 8. Lower scores on the each represent the better participant's condition, whereas, higher scores indicate worsening condition. | Baseline, Month 6 and 12 | 
| Percentage of Participants With Positive Response on Quality of Life Assessment of Growth Hormone [GH] Deficiency in Adults (QoL AGHDA) Scale | Quality of Life Assessment of GH Deficiency in Adults (QoL AGHDA) questionnaire consists of 25 items that evoke yes or no answers. A score of 1 is given to each item affirmed and these are summed to give the total score. The maximum score is 25, which represents a poor quality of life. The minimum score is 0, which represents a good quality of life. Each question has to be answered with a NO/YES and for each YES, one point is added. The more YES, the higher the score and the worse. Decrease in the positive responses is an index of improvement. So, when the percentage of positive responses on the scale decreases, it is considered a response rate. | Baseline, Month 6 and 12 |