Growth Hormone in Neuroendocrine Dysfunction With Severe Fibromyalgia Syndrome

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

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.

Study Overview

• Status: Completed
• Conditions: Fibromyalgia
• Intervention / Treatment: Drug: Saizen®; Drug: Placebo and Saizen®

• Study Type: Interventional
• Enrollment (Actual): 113
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain
    • Centro Medico Teknon, Endocrinology Department

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Saizen®	Drug: Saizen®; 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.; Other Names: Somatropin
Active Comparator: Placebo + Saizen®	Drug: Placebo and Saizen®; 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.

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

Collaborators and Investigators

• Sponsor: Merck KGaA, Darmstadt, Germany
• Collaborators: Merck, S.L., Spain
• Investigators: Principal Investigator: Guillem Cuatrecasas, MD, Centro Médico Teknon

Publications and helpful links

General Publications

• Cuatrecasas G, Alegre C, Fernandez-Sola J, Gonzalez MJ, Garcia-Fructuoso F, Poca-Dias V, Nadal A, Cuatrecasas G, Navarro F, Mera A, Lage M, Peino R, Casanueva F, Linan C, Sesmilo G, Coves MJ, Izquierdo JP, Alvarez I, Granados E, Puig-Domingo M. Growth hormone treatment for sustained pain reduction and improvement in quality of life in severe fibromyalgia. Pain. 2012 Jul;153(7):1382-1389. doi: 10.1016/j.pain.2012.02.012. Epub 2012 Mar 31.
• Cuatrecasas G, Gonzalez MJ, Alegre C, Sesmilo G, Fernandez-Sola J, Casanueva FF, Garcia-Fructuoso F, Poca-Dias V, Izquierdo JP, Puig-Domingo M. High prevalence of growth hormone deficiency in severe fibromyalgia syndromes. J Clin Endocrinol Metab. 2010 Sep;95(9):4331-7. doi: 10.1210/jc.2010-0061. Epub 2010 Jul 14.

Study record dates

Study Major Dates

• Study Start: December 1, 2007
• Primary Completion (Actual): July 1, 2010
• Study Completion (Actual): July 1, 2010

Study Registration Dates

• First Submitted: July 2, 2009
• First Submitted That Met QC Criteria: July 6, 2009
• First Posted (Estimate): July 7, 2009

Study Record Updates

• Last Update Posted (Estimate): August 2, 2013
• Last Update Submitted That Met QC Criteria: August 1, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Muscular Diseases; Neuromuscular Diseases; Fibromyalgia; Myofascial Pain Syndromes
• Other Study ID Numbers: 27560