Adults Growth Hormone Deficiency. Clinical Trial
Official title:
Effects of Pegvisomant-Priming With the Glucagon Stimulation Test in Assessing GH and Cortisol Reserve in Adults: a Randomized Proof-of-Concept Pilot Study
Hypothesis:
Pegvisomant combined with the glucagon stimulation test (GST) can improve the accuracy of
this test when used to diagnose adult GH and cortisol (steroid hormone)insufficiency.
Study aims:
Diagnosing GH and cortisol deficiency in adults requires a special test. At present, the
insulin tolerance test (ITT) is considered the test of choice. However, this test is
difficult to perform as it involves giving insulin through the veins to decrease blood
sugars to very low levels, and this can be unpleasant, and cannot be performed in elderly
adults and in those with a history of heart disease, seizure disorders or stroke. For this
reason there is an urgent need for an alternative reliable test. At present, the GST is
considered the alternative test to the ITT but its accuracy in obese patients and in those
with diabetes remains unclear. Pegvisomant is a medication that can increase GH production
in the body. The purpose of this study is to find out if combining pegvisomant with the GST
can help improve the accuracy of this test so that it is comparable with the ITT in
diagnosing adult GH and cortisol insufficiency.
Study design:
Subjects will be recruited from the Oregon Health & Science University Dynamic Endocrine
Testing Unit. A written informed consent will be obtained and a screening interview will be
carried out. During the screening interview, the study will be explained to the subject in
detail. For women of child-bearing age, a pregnancy test will be performed. The subjects
will then take part in three studies on separate days: (1) GST; (2) pegvisomant (1 mg/kg)
injection into the abdomen 3 days before the glucagon stimulation test (ii) insulin
tolerance test. For the GST, glucagon will be injected into the muscle and blood draws will
be performed every 30 mins for 240 mins. For the insulin tolerance test, a blood draw will
be performed and insulin will be given into the vein followed by blood draws every 15 mins
for 120 mins. The data from all three studies will be analyzed in the study where the peak
growth hormone and cortisol levels for all three tests will be compared. A questionnaire
will be used at the end of the study for the subjects to rank the level of preference of the
three tests. The data of the study will be analyzed using a computer statistical program
where the identity of the subjects will be coded to maintain confidentiality.
| Status | Recruiting |
| Enrollment | 10 |
| Est. completion date | December 2013 |
| Est. primary completion date | November 2013 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 21 Years to 55 Years |
| Eligibility |
Inclusion Criteria: - Ability to provide written informed consent and comply with study assessments for the full duration of the study. - Age 21 to 55 years - Body weight 60 to 120 kg inclusive - Stable weight and diet for at least 3 months prior to study entry Exclusion Criteria: - Poor IV access - Known hypersensitivity to glucagon - Inability or unwillingness to comply with study procedures - Clinically significant cardiovascular or cerebrovascular disease - Current active malignancy other than non-melanoma skin cancer - Active acromegaly or Cushing's disease - Pheochromocytoma - Pregnancy - Renal failure (serum creatinine > 2 mg/dl) - Severe acute illness - Uncontrolled hypertension (BP > 160/100 mmHg) - Emotional/social instability likely to prejudice study completion - Recurrent or severe unexplained hypoglycemia - Known or suspected drug/alcohol abuse - Patients with history of coronary artery disease, cerebrovascular disease, congestive heart failure, arrhythmias and seizure disorder that would be excluded from the ITT arm regardless of age - Participation in another simultaneous medical investigation or trial |
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Diagnostic
| Country | Name | City | State |
|---|---|---|---|
| United States | Oregon Health & Science University | Portland | Oregon |
| Lead Sponsor | Collaborator |
|---|---|
| Oregon Health and Science University | Aarhus University Hospital |
United States,
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Veldhuis JD, Bidlingmaier M, Anderson SM, Wu Z, Strasburger CJ. Lowering total plasma insulin-like growth factor I concentrations by way of a novel, potent, and selective growth hormone (GH) receptor antagonist, pegvisomant (B2036-peg), augments the amplitude of GH secretory bursts and elevates basal/nonpulsatile GH release in healthy women and men. J Clin Endocrinol Metab. 2001 Jul;86(7):3304-10. — View Citation
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| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Peak growth hormone and cortisol levels induced by the pegvisomant-glucagon test compared to those by the insulin tolerance test in assessing the growth hormone and cortisol reserve in adults suspected of adult growth hormone and cortisol deficiencies. | Presently, the insulin tolerance test (ITT) is regarded as the gold standard test in diagnosing adult GH deficiency but this test is difficult to perform in patients with diabetes mellitus, and contraindicated in the elderly, and in adults with seizures and ischemic heart disease. Glucagon test is the alternative test to the ITT but its accuracy and reliability is questionable in obesity and diabetes mellitus. Pegvisomant is a GH receptor blocker that increases GH secretion. When primed with glucagon, pegvisomant may enhance GH secretion by providing a stronger stimulus than glucagon alone. We plan to assess if by priming pegvisomant with glucagon will improve the accuracy of this test in diagnosing adult GH cortisol deficiency. Specifically, we will examine the characteristics of peak GH and cortisol levels, and ascertain the peak GH and cortisol levels in comparison to those generated using the ITT in diagnosing GH and cortisol deficiency. | 9 weeks | Yes |
| Secondary | Correlation of peak GH and cortisol levels to BMI and fasting glucose, and effects of pegvisomant on IGF-I bioactivity. | We plan to assess the correlation between peak growth hormone and cortisol levels induced by the pegvisomant-glucagon test and BMI, fasting blood glucose levels, and evaluate the effects of pegvisomant on insulin-like growth factor-I bioactivity using the insulin-like growth factor-I kinase receptor activity assay. | 9 weeks | Yes |