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

This study has been completed.
Sponsor:
Information provided by:
Merck KGaA
ClinicalTrials.gov Identifier:
NCT01060488
First received: January 29, 2010
Last updated: July 26, 2011
Last verified: July 2011
History of Changes
  Purpose

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:

U.S. FDA Resources

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.
  Eligibility

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

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 ClinicalTrials.gov identifier: NCT01060488

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

Publications:

Responsible Party: Dr. Laurence Fresneau, Merck Serono s.a.s., an Affiliate of Merck KGaA, Darmstadt, Germany
ClinicalTrials.gov 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
Dwarfism
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases
Bone Diseases, Endocrine
Hypopituitarism
Pituitary Diseases
 Hypothalamic Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Hormones
Growth Hormone-Releasing Hormone
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 23, 2013