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

Growth Hormone Deficiency Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01060488
• Other study ID #: IMP24689
• Status: Completed
• Phase: Phase 3
• First received: January 29, 2010
• Last updated: August 4, 2014
• Start date: January 2004

Study information

• Verified date: July 2011
• Source: Merck KGaA
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 69
• Est. primary completion date: November 2005
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Dwarfism, Pituitary
• Endocrine System Diseases
• Growth Hormone Deficiency

Intervention

Other:
• GHRH+Arg, GHRH+Arg, ITT
GHRH+Arg repeatability test (2 tests) + comparison with one IT test
• ITT, ITT, GHRH+Arg.
IT repeatability test (2 tests) + comparison with one GHRH+Arg test

Locations

Country	Name	City	State
France	CHU Bicêtre, Endocrinology and Reproductive Diseases Department	Le Kremlin Bicêtre

Sponsors (1)

Lead Sponsor	Collaborator
Merck KGaA

Country where clinical trial is conducted

France, 

References & Publications (1)

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 dia — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Level of GH peak (recorded following stimulation tests)		within 120 min after stimulation (blood samples were tacken at T0(before), T15, T30, T45, T60, T90 and T120 min after stimulation).	No
Secondary	It was asked to the patients to evaluate acceptability of each test via a visual analogic scale.		After each test and before leaving the hospital (the day of the test)	No