PREDnisolone-induced Beta-cell Dysfunction Prevented by EXenatide (PREDEX)

Prednisolone-induced Impairment of Glucose Metabolism and Beta-cell Dysfunction and the Protective Effects of Exenatide: a Single-center, Randomized, Double-blind, Placebo-controlled Crossover Study in Healthy Volunteers

The purpose of this study is to explore whether the GLP-1 receptor agonist exenatide, may prevent glucocorticoid-induced glucometabolic abnormalities and beta-cell dysfunction in healthy subjects.

Study Overview

• Status: Completed
• Conditions: Glucocorticoid-induced Glucometabolic Abnormalities; Glucocorticoid-induced Beta-cell Dysfunction
• Intervention / Treatment: Drug: Placebo; Drug: Prednisolone; Drug: Prednisolone and Exenatide

• Study Type: Interventional
• Enrollment (Anticipated): 8
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1081HV
      • VU University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• written informed consent
• 18 years ≤ age ≤ 35 years on the day of the first visit
• 22.0 ≤ BMI ≤ 28.0 kg/m2
• (History of) good physical and mental health as determined by history taking, physical and laboratory examinations and ECG.
• fasting glucose level of < 5.6 mmol/L, in addition to a glucose level of < 7.8 mmol/L at 2 hours after intake of 75 g glucose (OGTT).
• able to keep a normal day and night rhythm during the trial period (i.e. no shift work)

Exclusion Criteria:

• history or presence of a medical disorder
• use of drugs, except for incidental (non-opioid) analgesic agents
• first degree relative with T2DM
• performing intensive physical activity > 1x/week
• an allergic or anaphylactic reaction to prednisolone treatment in the past
• clinically relevant history or presence of any medical disorder, which are mentioned in the Summary of Product Characteristics (SPC) as contraindication for the use of prednisolone
• glucocorticosteroid use during the last three months prior to the first dose
• participation in an investigational drug trial within 90 days prior to the first dose
• donation of blood (> 100 mL) within 90 days prior to the first dose
• history of or current abuse of drugs or alcohol (>14 U/week)
• smoking
• use of grapefruit products during the study period
• recent changes in weight and/or physical activity
• serious mental impairment or language problems i.e. preventing to understand the study protocol/aim

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 2	Drug: Prednisolone; Single dose of 80 mg prednisolone with saline infusion
Placebo Comparator: 1	Drug: Placebo; Single dose of placebo with saline infusion
Active Comparator: 3	Drug: Prednisolone and Exenatide; Prednisolone 80 mg single dose Exenatide infusion 20 mg/min

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To assess whether a single day infusion of the GLP-1 RA exenatide, as compared to placebo, reverses GC-induced impairment of glucose metabolism in healthy males, quantified as glucose tolerance (AUCgluc) during a standardized mixed-meal test	Single-day treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
To assess whether a single day infusion of the GLP-1 RA exenatide, as compared to placebo, reverses GC-induced acute beta-cell dysfunction in healthy males, quantified as Various measures of beta-cell function	Single day treatment

Collaborators and Investigators

• Sponsor: Amsterdam UMC, location VUmc
• Collaborators: National Research Council, Institute of Biomedical Engineering
• Investigators: Principal Investigator: Michaela Diamant, MD PhD, Amsterdam UMC, location VUmc

Publications and helpful links

General Publications

• van Raalte DH, van Genugten RE, Linssen MM, Ouwens DM, Diamant M. Glucagon-like peptide-1 receptor agonist treatment prevents glucocorticoid-induced glucose intolerance and islet-cell dysfunction in humans. Diabetes Care. 2011 Feb;34(2):412-7. doi: 10.2337/dc10-1677. Epub 2011 Jan 7.

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Primary Completion (Actual): January 1, 2010
• Study Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: August 28, 2008
• First Submitted That Met QC Criteria: August 28, 2008
• First Posted (Estimate): August 29, 2008

Study Record Updates

• Last Update Posted (Estimate): January 13, 2010
• Last Update Submitted That Met QC Criteria: January 12, 2010
• Last Verified: January 1, 2010

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Congenital Abnormalities; Hypoglycemic Agents; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Anti-Obesity Agents; Incretins; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Exenatide
• Other Study ID Numbers: DC2008pred003