Comparative Validation of the Growth Hormone Releasing Hormone and Arginine Test for the Diagnosis of Adult Growth Hormone Deficiency

This study has been completed.
Information provided by:
Merck KGaA Identifier:
First received: January 29, 2010
Last updated: July 26, 2011
Last verified: July 2011

The aim of the study is to determine the specificity and sensitivity of the combined growth hormone releasing hormone (GHRH) + Arginine test in healthy volunteers, subjects with highly probable adult growth hormone deficiency (AGHD) and subjects who were probably free of AGHD.

Condition Intervention Phase
Growth Hormone Deficiency
Other: GHRH+Arg, GHRH+Arg, ITT
Other: ITT, ITT, GHRH+Arg.
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: A Phase III, Multicentric, Open-label, Randomised, Comparative, Parallel Group Study of (GHRH + Arginine) Combination Test vs. Insulin Tolerance Test (ITT) in the Diagnosis of Adult Growth Hormone Deficiency (AGHD)

Resource links provided by NLM:

Further study details as provided by Merck KGaA:

Primary Outcome Measures:
  • Level of GH peak (recorded following stimulation tests) [ Time Frame: within 120 min after stimulation (blood samples were tacken at T0(before), T15, T30, T45, T60, T90 and T120 min after stimulation). ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • It was asked to the patients to evaluate acceptability of each test via a visual analogic scale. [ Time Frame: After each test and before leaving the hospital (the day of the test) ] [ Designated as safety issue: No ]

Enrollment: 69
Study Start Date: January 2004
Primary Completion Date: November 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Group 1: Other: GHRH+Arg, GHRH+Arg, ITT
GHRH+Arg repeatability test (2 tests) + comparison with one IT test
Active Comparator: Group 2: Other: ITT, ITT, GHRH+Arg.
IT repeatability test (2 tests) + comparison with one GHRH+Arg test

Detailed Description:

The randomisation was carried out before the first test was performed. In order to be informed of the subject's randomisation group, the investigator phoned the access number given to him/her. The subject's allocation to a given randomisation arm was determined on the basis of a centralised randomisation (answering service), balanced per group of subjects with a minimisation on 2 criteria: age and BMI.

This was a centralised randomisation using a Interactive Voice Response System (IVRS) which was balanced in each of the following 3 categories of subjects:

  • Category A = healthy volunteers,
  • Category B = subjects with a strong probability of deficit in GH,
  • Category C = subjects with a low probability of deficit in GH.

In each of these 3 categories, the subjects underwent 3 tests whose sequences were determined by the following randomisation group:

  • Group 1: GHRH+Arg, GHRH+Arg, ITT or
  • Group 2: ITT, ITT, GHRH+Arg.

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • Subjects aged over 18 years and under 60 years,
  • Female or male,
  • Subjects not treated by GH or having stopped the treatment more than 15 days ago,
  • Effective contraception in women of childbearing age: hormonal contraception or use of female condom and spermicides or use of diaphragm and spermicides or Intra Uterine Device (IUD),
  • Signed informed consent,
  • Subjects possessing social security cover.
  • Subjects having at least one of the following criteria were considered as subjects with a high probability of presenting a GH deficit:

    • Subjects with a tumour of the hypothalamo-hypophyseal region (hypophyseal adenomata, craniopharyngioma, meningioma, etc.) in whom the presence of a hypophyseal insufficiency in GH must be tested preoperatively or postoperatively, or
    • Subjects presenting a secondary ante-hypophyseal insufficiency to an inflammatory, infectious, post-traumatic pathology or to a hypophyseal necrosis, whose hypophyseal functional condition has already been documented and for whom a revaluation of GH secretion is desired, or
    • Subjects having undergone, as adults, an irradiation hypothalamo-hypophyseal region, or a suprasellar irradiation, in a clinical context of GH deficit, or
    • Subjects with a known organic ante-hypophyseal insufficiency beginning in childhood and with at least 1 associated deficit excluding prolactin.
  • Subjects having at least one of the following criteria were considered as subjects with a low probability of presenting a GH deficit:

    • Subjects with known idiopathic isolated GH deficit starting in childhood and for whom a new growth hormone secretion test is desired, or
    • Subjects with non-operated microadenoma (< 1 cm of diameter), or
    • Subjects with fortuitously discovered intrasellar image (e.g. Rathke's pocket cyst).

The third category of subjects eligible was made of healthy volunteers.

Exclusion Criteria:

  • Subjects presenting a coronary history or whose electrocardiographic signs evoke an ischemic pathology,
  • Subjects presenting a history of cerebrovascular insufficiency,
  • Subjects presenting a history of epilepsy,
  • Subjects with an evolutive acromegalia or an evolutive Cushing's syndrome,
  • Subjects presenting a known intolerance to arginine, GHRH or insulin,
  • Hyperkalemic subjects,
  • Diabetic subjects (Type 1 or Type 2),
  • Very obese subjects (BMI > 40),
  • Subjects presenting a severe, hepatic, renal, tumoral evolutive affection or metabolic or respiratory acidosis,
  • Subjects with known immuno-depression,
  • Subjects with psychiatric disorders,
  • Subjects presenting Parkinson's disease or Parkinsonian syndromes treated by Levodopa®,
  • Subjects treated by drugs directly affecting the hypophyseal secretion of somatotrophin (e.g. clonidine, levodopa) or provoking the release of somatostatin, antimuscarinic agents (atropine),
  • Subjects with untreated hypothyroidism or subjects treated by anti-thyroid synthesis drugs,
  • Participation in another biomedical research programme less than 3 months previously,
  • Known evolutive pregnancy or breastfeeding.
  Contacts and Locations
Please refer to this study by its identifier: NCT01060488

CHU Bicêtre, Endocrinology and Reproductive Diseases Department
Le Kremlin Bicêtre, France
Sponsors and Collaborators
Merck KGaA
Principal Investigator: Philippe Chanson, MD, Professor CHU Bicêtre, Endocrinology and Reproductive Diseases Department
  More Information

Responsible Party: Dr. Laurence Fresneau, Merck Serono s.a.s., an Affiliate of Merck KGaA, Darmstadt, Germany Identifier: NCT01060488     History of Changes
Other Study ID Numbers: IMP24689
Study First Received: January 29, 2010
Last Updated: July 26, 2011
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Merck KGaA:
GH secretion tests
adverse effects
adult growth hormone deficiency
growth-hormone releasing hormone and arginine test
insulin tolerance test
GHRH + Arginine test
Insulin Tolerance Test

Additional relevant MeSH terms:
Dwarfism, Pituitary
Endocrine System Diseases
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases
Bone Diseases, Endocrine
Pituitary Diseases
Hypothalamic Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Growth Hormone-Releasing Hormone
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions processed this record on April 15, 2014