Pegvisomant With Glucagon Test to Assess for Adult Growth Hormone Deficiency

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by Oregon Health and Science University
Sponsor:
Collaborator:
Aarhus University Hospital
Information provided by (Responsible Party):
Kevin Yuen, Oregon Health and Science University
ClinicalTrials.gov Identifier:
NCT01804413
First received: February 18, 2013
Last updated: October 23, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention
Adults Growth Hormone Deficiency.
Drug: Pegvisomant
Drug: Regular insulin

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Diagnostic
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

Resource links provided by NLM:


Further study details as provided by Oregon Health and Science University:

Primary Outcome Measures:
  • 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. [ Time Frame: 9 weeks ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Correlation of peak GH and cortisol levels to BMI and fasting glucose, and effects of pegvisomant on IGF-I bioactivity. [ Time Frame: 9 weeks ] [ Designated as safety issue: Yes ]
    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.


Estimated Enrollment: 10
Study Start Date: March 2011
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Pegvisomant-glucagon test
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
Pegvisomant 1 mg/kg injection 3 days before the glucagon test.
Other Name: Somavert.
Drug: Regular insulin
0.1-0.15 units/kg
Active Comparator: Insulin tolerance test
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
0.1-0.15 units/kg

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   21 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01804413

Contacts
Contact: Kevin C.J. Yuen, MRCP(UK),MD 503 4940175 yuenk@ohsu.edu
Contact: Sharon A. Rhoads, RN 503 4949197 rhoadss@ohsu.edu

Locations
United States, Oregon
Oregon Health & Science University Recruiting
Portland, Oregon, United States, 97239
Contact: Kevin C.J. Yuen, MRCP(UK),MD    503 4940175    yuenk@ohsu.edu   
Contact: Sharon A. Rhoads, RN    503 4949197    rhoadss@ohsu.edu   
Sub-Investigator: David M. Cook, MD         
Sponsors and Collaborators
Oregon Health and Science University
Aarhus University Hospital
  More Information

Publications:

Responsible Party: Kevin Yuen, Associate Professor of Endocrinology, Oregon Health and Science University
ClinicalTrials.gov Identifier: NCT01804413     History of Changes
Other Study ID Numbers: IRB6961
Study First Received: February 18, 2013
Last Updated: October 23, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Oregon Health and Science University:
Pegvisomant
Growth hormone
Cortisol
Glucagon
Insulin

Additional relevant MeSH terms:
Pituitary Diseases
Dwarfism, Pituitary
Endocrine System Diseases
Dwarfism
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases
Bone Diseases, Endocrine
Hypopituitarism
Hypothalamic Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Glucagon
Glucagon-Like Peptide 1
Hormones
Insulin
Hydrocortisone
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Gastrointestinal Agents
Therapeutic Uses
Incretins
Hypoglycemic Agents
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on July 22, 2014