GH and Cardiovascular Risk Factors

Study Overview
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Brief Summary
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Rationale: Abnormally low and high levels of insulin-like growth factor-I (IGF-I) are both associated with increased metabolic risk. Since (U-shaped) associations of IGF-I, within the normal range, have also been found with cardiovascular risk factors and disease in the general population, it would be interesting to investigate if this association can also be found in growth hormone deficient (GHD) adults treated with Growth Hormone (GH). This could be of interest for endocrinologists prescribing GH in clinical practice because strict dosing may become even more important. Next to that, scientific evidence for clinical practice is wanted. Objective: Next to cardiovascular risk factors (main objectives: body composition and lipid profile; secondary objectives: remainder) we investigate the effect on glucose metabolism, physical performance, and neuropsychological functioning of different levels of IGF-I in GH treated GHD men and women. Study design: Open-label randomized trial. Study population: At least 32 subjects, both childhood as adult onset GHD men and women, receiving GH treatment for at least one year, with an age between 20 and 65 years. Intervention: At entry subjects are already receiving GH treatment according to general clinical practice, and are expected to demonstrate an IGF-I concentration of 0 - 1 SD score (SDS) (normal dose). The group of men and group of women will be randomized to receive either a decrease of their regular dose of GH treatment (IGF-I target level of -2 - -1 SDS) (low dose), or an increase of their regular dose, (IGF-I target level of 1 - 2 SDS) (high dose) for at least 24 weeks.

Official Title
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Effect of Growth Hormone Replacement Therapy on Cardiovascular Risk Factors in Adult Patients With Severe Growth Hormone Deficiency: Association With IGF-I Concentration

Conditions
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Growth Hormone Deficiency, Cardiovascular Diseases, Metabolic Syndrome, Cognition, Physical Activity

Intervention / Treatment
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* Drug: Change in daily dosage of Growth Hormone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ongoing surveillance at our centre (VUmc) Stable substitution therapy for other pituitary hormone deficiencies Exclusion Criteria: Subjects with a craniopharyngioma as cause of their GHD or pituitary deficiencies Contraindications for the use of GH treatment (Receiving treatment for) malignant disease (in the past) Cardiovascular event less than one year prior to inclusion Participation in other studies Subjects, who in the opinion of the investigator, are unsuitable in any other way to participate in this study

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Low dose Growth Hormone<br>Halve of the group of men and group of women will receive a decrease of their regular dose of Growth Hormone treatment, with the IGF-I target level of -2 - -1 SD score (low dose=LD). | Drug: Change in daily dosage of Growth Hormone<br> <br> * Other names: Change in daily dosage of Somatropin;|
| Active Comparator: High dose Growth Hormone<br>Halve of the group of men and group of women will receive an increase of their regular dose of Growth Hormone treatment, with the IGF-I target level of 1 - 2 SD score (high dose=HD). | Drug: Change in daily dosage of Growth Hormone<br> <br> * Other names: Change in daily dosage of Somatropin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cardiovascular risk (body composition and lipid profile) |  | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cardiovascular risk (inflammatory markers, vascular stiffness, endothelial function, presence of the metabolic syndrome) |  | 24 weeks | 
| Change in physical performance (muscle strength, physical activity) |  | 24 weeks | 
| Change in glucose metabolism (fasting and 2hr postprandial glucose, insulin resistance) |  | 24 weeks | 
| Change in neuropsychological functioning (QoL, cognition, mood) |  | 24 weeks |