Clinical Trial: The ORIGIN Trial (Outcome Reduction with Initial Glargine Intervention)


	Home	\|	Search	\|	Browse	\|	Resources	\|	Help	\|	What's New	\|	About

Sponsored by:	Aventis Pharmaceuticals
Information provided by:	Aventis Pharmaceuticals

Condition	Treatment or Intervention	Phase
Diabetes Mellitus, Non-Insulin-Dependent	Drug: Lantus injection Drug: Omacor (ethyl esters of omega-3 polyunsaturated fatty acids)	Phase III

Study Type: Interventional
Study Design: Treatment, Randomized, Open Label, Active Control, Factorial Assignment, Efficacy Study

Official Title: A Multicenter, International Randomized, 2x2 Factorial Design Study to Evaluate the Effects of Lantus (Insulin Glargine) versus Standard Care, and of Omega-3 Fatty Acids versus Placebo, in reducing Cardiovascular Morbidity and Mortality in High Risk People with Impaired Fasting Glucose (IFG), Impaired Glucose Tolerance (IGT) or Early Type 2 Diabetes Mellitus: The ORIGIN Trial (Outcome Reduction with Initial Glargine Intervention)

Inclusion criteria:

Glucose tolerance status for all candidates who are not known to have diabetes will be determined on the basis of a 75 gram oral glucose tolerance test (OGTT) that will be performed fasting (i.e. no consumption of food or beverage other than water for at least 8 hours). Two plasma glucose values will be drawn during this OGTT – a fasting value and a value drawn two hours after the 75g oral glucose load is administered (PPG).

1.Participants must have one of the following:

Impaired glucose tolerance (IGT), defined as a postprandial plasma glucose value (PPG) ≥ 140 and < 200 mg/dL (≥ 7.8 and < 11.1 mM), with FPG < 126 mg/dL (7.0 mM).
OR Impaired fasting glucose (IFG), defined as a fasting plasma glucose (FPG) ≥.110 and <.126 mg/dL (≥.6.1 and < 7 mM), without diabetes mellitus (PPG must be < 200 mg/dL [11.1 mM]).
OR Early type 2 diabetes, defined as a FPG ≥ 126 mg/dL (7.0 mM) or a PPG of 200 mg/dL (11.1 mM) or greater, or a previous diagnosis of diabetes, and either: on no pharmacological treatment for at least 10 weeks prior to screening, with screening glycated hemoglobin < 150% of the upper limit of normal for the laboratory ( eg. < 9% if the upper limit is 6%)
OR taking one oral antidiabetic drug (OAD: from among sulfonylureas, biguanides, thiazolidinediones, alpha-glucosidase inhibitors, and meglitinides) at a stable dose for at least 10 weeks at the time of screening (or for the 10 weeks prior to hospitalization if identified while hospitalized for a CV event), with screening glycated hemoglobin < 133% of the upper limit of normal for the laboratory (eg. <.8% if the upper limit is 6%) if taking this medication at half-maximum dose or greater, and glycated hemoglobin < 142% of the upper limit of normal for the laboratory ( eg. < 8.5% if the upper limit is 6%) if taking this medication at less than half-maximum dose.

2. Men or women aged 50 years and older

3. Participants must be at risk for cardiovascular disease, based on satisfying one or more of the following criteria:

prior myocardial infarction (MI) (≥ 5 days prior to randomization)
prior stroke (≥ 5 days prior to randomization)
prior coronary, carotid or peripheral arterial revascularization
angina with documented ischemic changes (at least 2 mm ST segment depression on ECG during a Graded Exercise Test [GXT]; or with a cardiac imaging study positive for ischemia); or unstable angina with documented ischemic changes (either ST segment depression of at least 1 mm or an increase in troponin above the normal range but below the range diagnostic for acute myocardial infarction)
microalbuminuria or clinical albuminuria (an albumin: creatinine ratio > 30 mg/mg in a first morning urine sample, per ADA criteria of Jan. 2001)
left ventricular hypertrophy by electrocardiogram or echocardiogram
at least 50% stenosis on angiography of a coronary, carotid, or lower extremity artery
ankle/brachial index < 0.9.

4. Provision of signed and dated informed consent prior to any study procedures.

5. Ability and willingness to complete study diaries and questionnaires.

6. Demonstrated ability to use the self-glucose-monitoring device, and to self-inject insulin prior to randomization.

7. A negative pregnancy test for all females of childbearing potential.

8. Willingness to discontinue prior omega-3 PUFA supplements for the duration of the study.

Exclusion criteria

1. Type 1 diabetes.

2. Requiring insulin treatment.

3. Known anti-GAD Ab positivity in the past.

4. Screening glycated hemoglobin ≥ 150% of the upper limit of normal for the 5.laboratory (eg. ≥.9% if the upper limit is 6%).

5. Unwilling to inject insulin or perform self-monitoring of blood glucose

6. Nonadherence with the run-in requirement to inject placebo insulin and do capillary glucose monitoring for at least 4 days prior to randomization.

7. Coronary artery bypass grafting (CABG) within the 4 years prior to screening – however, patients with a MI or angina since a previous CABG will be eligible for randomization, even if the last CABG was within 4 years

8. Serum creatinine > 2.0 mg/dL (176 μM) at screening.

9. Active liver disease, or ALT or AST > 2.5 times upper limit of normal at screening.

10. Chronic or recurrent treatment with systemic corticosteroids, or niacin treatment for hyperlipidemia.

11. Heart failure of NYHA Functional Class III or IV.

12. Expected survival of < 3 years for non- cardiovascular causes, or cancer other than non-melanoma skin cancer within last 3 years.

13. Any other factor likely to limit protocol compliance or reporting of adverse events.

14. Unwilling or unable to discontinue thiazolidinediones.

15. Simultaneous participation in any other clinical trial of an active pharmacologic agent.

16. Unwillingness to permit sites to contact their primary physicians to communicate information about the study and the participant’s data and treatment assignment.

17. History of hypersensitivity to the investigational products.

18. Previous randomization in this study.

19. A prior heart transplant, or awaiting a heart transplant.