IL-1RA, Acute Exercise, and Beta-cell Function

Study Overview
=================
Brief Summary
-----------------
Subjects (N=48) with poorly-controlled type 2 diabetes (HbA1c>7%) will be assigned to one of the 4 following interventions in a randomised, parallel group design: [I] Control (placebo injection; no exercise), [II] Anakinra (100 mg subcutaneous injection of human recombinant interleukin-1 receptor antagonist), [III] Exercise (1 h cycle ergometry at 75% VO2max), [IV] Anakinra + Exercise. Pancreatic beta-cell function (plasma insulin responses) will be measured before and after each intervention using a hyperglycemic clamp (5.4 mM above basal glucose) combined with GLP-1 infusion (0.5 pmol/kg/min) and arginine injection (5 g bolus).

Conditions
-----------------
Type 2 Diabetes Mellitus

Intervention / Treatment
-----------------
* Drug: Anakinra (AN)
* Behavioral: Exercise (EX)
* Behavioral: Control (CON)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Type 2 diabetes with HbA1c >7% Exclusion Criteria: HbA1c >7% Age <30 or >80 y BMI <25 or >40 kg/m2 Pregnancy Evidence of chronic haematological/renal/hepatic/pulmonary/heart disease >2kg weight change in prior 6 months Alcohol consumption (men: >14 drinks/week; women: >7 drinks/week) Smoking Physical activity of >150 min/week Contraindication to exercise Contraindication to use of anakinra

Ages Eligible for Study
-----------------
Minimum Age: 30 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Control (CON)<br>Placebo will be administered as a subcutaneous injectable bolus, the day prior to the repeated measurement of beta-cell function. | Behavioral: Control (CON)<br> <br> |
| Experimental: Anakinra (AN)<br>100 mg of Kineret (Anakinra) will be administered as a subcutaneous injectable bolus, the day prior to the repeated measurement of beta-cell function. | Drug: Anakinra (AN)<br> <br> |
| Experimental: Exercise (EX)<br>1 hour of cycling exercise will be performed at 75% VO2max, the day prior to the repeated measurement of beta-cell function. | Behavioral: Exercise (EX)<br> <br> |
| Experimental: Anakinra + Exercise (ANEX)<br>100 mg of Kineret (Anakinra) will be administered as a subcutaneous injectable bolus followed by 1 hour of cycling exercise at 75% VO2max, the day prior to the repeated measurement of beta-cell function. | Drug: Anakinra (AN)<br> <br> Behavioral: Exercise (EX)<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Beta-cell function | A hyperglycemic clamp will be performed combined with glucagon-like peptide(GLP)-1 infusion and arginine injection. The primary outcome is the insulin secretory response to glucose, GLP-1, and arginine. | 1 day after intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucose disposition | The glucose disposal rate during hyperglycemic clamp | 1 day after intervention | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Exercise, IL-1RA, Beta-cell function, Type 2 Diabetes