Pegvisomant With Glucagon Test to Assess for Adult Growth Hormone Deficiency

NCT01804413 | Unknown

• 1 other identifier: IRB6961
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Adults Growth Hormone Deficiency.

Keywords

Pegvisomant; Growth hormone; Cortisol; Glucagon; Insulin

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• Correlation of peak GH and cortisol levels to BMI and fasting glucose, and effects of pegvisomant on IGF-I bioactivity.

  9 weeks

Study Arms (2)

Pegvisomant-glucagon test

ACTIVE COMPARATOR

To compare the combined pegvisomant with the glucagon test to the insulin tolerance test and the glucagon test in diagnosing adult growth hormone and cortisol insufficiency.

Drug: Pegvisomant; Drug: Regular insulin

Insulin tolerance test

ACTIVE COMPARATOR

To compare the combined pegvisomant with the glucagon test to the insulin tolerance test and the glucagon test in diagnosing adult growth hormone and cortisol insufficiency.

Drug: Regular insulin

Interventions

Pegvisomant DRUG

Pegvisomant 1 mg/kg injection 3 days before the glucagon test.

Also known as: Somavert.

Pegvisomant-glucagon test

Regular insulin DRUG

0.1-0.15 units/kg

Insulin tolerance test; Pegvisomant-glucagon test

Eligibility Criteria

• Age: 21 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Oregon Health and Science University: lead
• Aarhus University Hospital: collaborator

Study Sites (1)

Oregon Health & Science University

Portland, Oregon, 97239, United States

RECRUITING

Related Publications (9)

• Yuen KC, Biller BM, Molitch ME, Cook DM. Clinical review: Is lack of recombinant growth hormone (GH)-releasing hormone in the United States a setback or time to consider glucagon testing for adult GH deficiency? J Clin Endocrinol Metab. 2009 Aug;94(8):2702-7. doi: 10.1210/jc.2009-0299. Epub 2009 Jun 9.

  PMID: 19509104 BACKGROUND

• Berg C, Meinel T, Lahner H, Yuece A, Mann K, Petersenn S. Diagnostic utility of the glucagon stimulation test in comparison to the insulin tolerance test in patients following pituitary surgery. Eur J Endocrinol. 2010 Mar;162(3):477-82. doi: 10.1530/EJE-09-0824. Epub 2009 Dec 8.

  PMID: 19996199 BACKGROUND

• Conceicao FL, da Costa e Silva A, Leal Costa AJ, Vaisman M. Glucagon stimulation test for the diagnosis of GH deficiency in adults. J Endocrinol Invest. 2003 Nov;26(11):1065-70. doi: 10.1007/BF03345251.

  PMID: 15008242 BACKGROUND

• Gomez JM, Espadero RM, Escobar-Jimenez F, Hawkins F, Pico A, Herrera-Pombo JL, Vilardell E, Duran A, Mesa J, Faure E, Sanmarti A. Growth hormone release after glucagon as a reliable test of growth hormone assessment in adults. Clin Endocrinol (Oxf). 2002 Mar;56(3):329-34. doi: 10.1046/j.1365-2265.2002.01472.x.

  PMID: 11940044 BACKGROUND

• di Iorgi N, Napoli F, Allegri A, Secco A, Calandra E, Calcagno A, Frassinetti C, Ghezzi M, Ambrosini L, Parodi S, Gastaldi R, Loche S, Maghnie M. The accuracy of the glucagon test compared to the insulin tolerance test in the diagnosis of adrenal insufficiency in young children with growth hormone deficiency. J Clin Endocrinol Metab. 2010 May;95(5):2132-9. doi: 10.1210/jc.2009-2697. Epub 2010 Mar 29.

  PMID: 20350939 BACKGROUND

• 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. doi: 10.1210/jcem.86.7.7656.

  PMID: 11443205 BACKGROUND

• Veldhuis JD, Bidlingmaier M, Anderson SM, Evans WS, Wu Z, Strasburger CJ. Impact of experimental blockade of peripheral growth hormone (GH) receptors on the kinetics of endogenous and exogenous GH removal in healthy women and men. J Clin Endocrinol Metab. 2002 Dec;87(12):5737-45. doi: 10.1210/jc.2001-011885.

  PMID: 12466380 BACKGROUND

• Radetti G, Wu Z, Elsedfy HH, El Kholy M, Bozzola M, Strasburger CJ. Pegvisomant-primed GH stimulation test. Clin Endocrinol (Oxf). 2008 Jun;68(6):951-6. doi: 10.1111/j.1365-2265.2007.03132.x. Epub 2007 Nov 19.

  PMID: 18031320 BACKGROUND

• Yuen KC, Frystyk J, Rhoads SA, Bidlingmaier M. Pegvisomant-primed glucagon stimulation test in assessing GH reserve and GH/IGF kinetics in adults suspected of GH deficiency. Pituitary. 2016 Feb;19(1):65-74. doi: 10.1007/s11102-015-0688-8.

  PMID: 26496767 DERIVED

MeSH Terms

Conditions

Insulin Resistance

Interventions

pegvisomant; Insulin

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Central Study Contacts

Kevin C.J. Yuen, MRCP(UK),MD

CONTACT

503 4940175; yuenk@ohsu.edu

Sharon A. Rhoads, RN

CONTACT

503 4949197; rhoadss@ohsu.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Endocrinology

Study Record Dates

• First Submitted: February 18, 2013
• First Posted: March 5, 2013
• Study Start: March 1, 2011
• Primary Completion: November 1, 2013
• Study Completion: December 1, 2013
• Last Updated: October 24, 2013

Record last verified: 2013-10

Locations

US (1)