Effects of "in UTERO" Exposure to Glucocorticoids (GLUCODEX)

Study of the Effects in Carbohydrate Metabolism and Renal Function of "in UTERO" Exposure to Glucocorticoids in Adult Offsprings (GLUCODEX)

The main objective of this study is to show that the fetal exposure to excess of glucocorticoids is associated with a deficiency of the function beta insulin in the offspring adult.

Study Overview

• Status: Unknown
• Conditions: 21-hydroxylase; Defect
• Intervention / Treatment: Procedure: Euglycemic hyperinsulinemic clamp

Detailed Description

The main objective of this study is to show that the fetal exposure to excess of glucocorticoids is associated with a deficiency of the function beta insulin in the offspring adult 23 subjects of exposed offspring will be compared to 23 controls

• Study Type: Interventional
• Enrollment (Anticipated): 46
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Paris, France, 75010
    • Hopital Saint Louis
  • Paris, France
    • Professor GAUTIER

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Over 18 years Aged
• Males
• Women of childbearing age with a reliable and effective contraception for over 2 months
• Taking dexamethasone between the 6th and the 24th week of gestation by the mother with bloc 21-hydroxylase or normal pregnancy for control subjects
• Normal blood pressure and heart rate measured at rest: systolic blood pressure <= 150 mmHg, diastolic blood pressure <= 90 mmHg, heart rate between 55 and 90 beats/mn.
• Normal laboratory tests or not clinically significant abnormality NFS, platelets PT, aPTT, fibrin TP, TCA, Serum electrolytes, urea, creatinine Uric acid Triglycerides, total cholesterol, HDL cholesterol
• Fating bood glucose <= 6.9 mmol/l (exclusion criteria for diabetes from the American Diabetes Association) during the OGTT.
• Negative blood HCG
• Accepting the constraints of the protocol and had signed informed and free consent.
• Affiliated to the Social Security.

Exclusion Criteria:

• Affected offspring of 21-hydroxylase enzyme block
• Taking dexamethasone until pregnancy term by the mother of the subject
• Type 2 diabetes in one of the two parents and/or 1 of the 4 grandparents
• Pregnancy, Breastfeeding
• Body Mass Index (weight/height2)> 50 kg/m2
• Poisoning smoking (>10 cigarettes per day, whatever the duration of intoxication)
• Any drug taken apart from minor analgesics (aspirin, paracetamol) for less than 8 days at the inclusion and oral contraception
• Taking recent (less than 3 months) glucocorticoids either taken orally, by inhalation or percutaneously
• Current infections or recent infections (<10 days)
• Neoplastic disorders (with the exception of carcinoma in situ of the cervix or cutaneous epithelioma), haematological, cardiovascular, psychiatric, neurological
• Having donated blood or participated in a trial within 2 months preceding their inclusion

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: exposed offspring	Procedure: Euglycemic hyperinsulinemic clamp; Euglycemic hyperinsulinemic clamp will be performed at day 2
Other: controls	Procedure: Euglycemic hyperinsulinemic clamp; Euglycemic hyperinsulinemic clamp will be performed at day 2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glucose Tolerance	the tolerance will be measured by the area under the curve (AUC) of insulin secretion flow	3 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Insulin Sensitivity	3 days
Flow measurement of insulin secretory response to intravenous glucose	3 days
Measurement of the secretion of insulin and glucagon in response to arginine	3 days

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Jean-François GAUTIER, MD, Assistance Publique - Hôpitaux de Paris

Publications and helpful links

General Publications

• Riveline JP, Baz B, Nguewa JL, Vidal-Trecan T, Ibrahim F, Boudou P, Vicaut E, Brac de la Perrière A, Fetita S, Bréant B, Blondeau B, Tardy-Guidollet V, Morel Y, Gautier JF. Exposure to Glucocorticoids in the First Part of Fetal Life is Associated with Insulin Secretory Defect in Adult Humans. J Clin Endocrinol Metab. 2020 Mar 1;105(3). pii: dgz145. doi: 10.1210/clinem/dgz145.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2012
• Primary Completion (Anticipated): June 1, 2018
• Study Completion (Anticipated): June 1, 2018

Study Registration Dates

• First Submitted: May 24, 2011
• First Submitted That Met QC Criteria: June 3, 2011
• First Posted (Estimate): June 6, 2011

Study Record Updates

• Last Update Posted (Actual): December 21, 2017
• Last Update Submitted That Met QC Criteria: December 20, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: offspring of 21-hydroxylase enzyme block
• Other Study ID Numbers: P081209