Clinical trial NCT01060488: Comparative Validation of the Growth Hormone Releasing Hormone and Arginine Test for the Diagnosis of Adult Growth Hormone Deficiency
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Growth Hormone Deficiency
Keywords: GH secretion tests
adverse effects
adult growth hormone deficiency
growth-hormone releasing hormone and arginine test
insulin tolerance test
GHRH + Arginine test
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2010-02-02
Enrollment: 69
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: 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.

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 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.

Primary outcomes:
measure: Level of GH peak (recorded following stimulation tests)
timeFrame: within 120 min after stimulation (blood samples were tacken at T0(before), T15, T30, T45, T60, T90 and T120 min after stimulation).
Secondary outcomes:
measure: It was asked to the patients to evaluate acceptability of each test via a visual analogic scale.
timeFrame: After each test and before leaving the hospital (the day of the test)
Other outcomes:
Locations:
city: Le Kremlin Bicêtre
country: France
facility: CHU Bicêtre, Endocrinology and Reproductive Diseases Department
Study officials:
affiliation: CHU Bicêtre, Endocrinology and Reproductive Diseases Department
name: Philippe Chanson, MD, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chanson P, Cailleux-Bounacer A, Kuhn JM, Weryha G, Chabre O, Borson-Chazot F, Dubois S, Vincent-Dejean C, Brue T, Fedou C, Bresson JL, Demolis P, Souberbielle JC. Comparative validation of the growth hormone-releasing hormone and arginine test for the diagnosis of adult growth hormone deficiency using a growth hormone assay conforming to recent international recommendations. J Clin Endocrinol Metab. 2010 Aug;95(8):3684-92. doi: 10.1210/jc.2010-0295. Epub 2010 May 19.