Growth Hormone in Neuroendocrine Dysfunction With Severe Fibromyalgia Syndrome
Primary Purpose
Fibromyalgia
Status
Completed
Phase
Phase 3
Locations
Spain
Study Type
Interventional
Intervention
Saizen®
Placebo and Saizen®
Sponsored by
About this trial
This is an interventional treatment trial for Fibromyalgia
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
Sites / Locations
- Centro Medico Teknon, Endocrinology Department
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Saizen®
Placebo + Saizen®
Arm Description
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
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).
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.
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.
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.
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.
Full Information
NCT ID
NCT00933686
First Posted
July 2, 2009
Last Updated
August 1, 2013
Sponsor
Merck KGaA, Darmstadt, Germany
Collaborators
Merck, S.L., Spain
1. Study Identification
Unique Protocol Identification Number
NCT00933686
Brief Title
Growth Hormone in Neuroendocrine Dysfunction With Severe Fibromyalgia Syndrome
Official Title
Growth Hormone Treatment of Severe Fibromyalgia Syndrome Associated With Functional Failure of Somatotropic Axis. A Multicentre, Randomized, Double-blind, Placebo-controlled Study.
Study Type
Interventional
2. Study Status
Record Verification Date
August 2013
Overall Recruitment Status
Completed
Study Start Date
December 2007 (undefined)
Primary Completion Date
July 2010 (Actual)
Study Completion Date
July 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck KGaA, Darmstadt, Germany
Collaborators
Merck, S.L., Spain
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fibromyalgia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
113 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Saizen®
Arm Type
Active Comparator
Arm Title
Placebo + Saizen®
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Saizen®
Other Intervention Name(s)
Somatropin
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo and Saizen®
Intervention Description
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.
Primary Outcome Measure Information:
Title
Percentage of Participants With Less Than 11 Tender Points at Month 6
Description
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.
Time Frame
Month 6
Title
Percentage of Participants With Less Than 11 Tender Points at Month 12
Description
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.
Time Frame
Month 12
Secondary Outcome Measure Information:
Title
Fibromyalgia Impact Questionnaire (FIQ) Total Score
Description
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).
Time Frame
Baseline, Month 1, 3, 6, 7, 9 and 12
Title
Visual Analog Scale (VAS) Total Score
Description
Visual Analog Scale (VAS) is a 100 millimeter (mm) scale. Intensity of pain range: 0 mm=no pain to 100 mm=worst possible pain.
Time Frame
Baseline, Month 1, 3, 6, 7, 9 and 12
Title
EuroQol 5-Dimensions (EQ-5D) Total Score
Description
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.
Time Frame
Baseline, Month 1, 3, 6, 7, 9 and 12
Title
Multidimensional Assessment of Fatigue (MAF) Total Score
Description
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.
Time Frame
Baseline, Month 6 and 12
Title
Percentage of Participants With Positive Response on Quality of Life Assessment of Growth Hormone [GH] Deficiency in Adults (QoL AGHDA) Scale
Description
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.
Time Frame
Baseline, Month 6 and 12
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Guillem Cuatrecasas, MD
Organizational Affiliation
Centro Medico Teknon
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centro Medico Teknon, Endocrinology Department
City
Barcelona
Country
Spain
12. IPD Sharing Statement
Citations:
PubMed Identifier
22465047
Citation
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.
Results Reference
derived
PubMed Identifier
20631018
Citation
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.
Results Reference
derived
Learn more about this trial
Growth Hormone in Neuroendocrine Dysfunction With Severe Fibromyalgia Syndrome
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