Effect of Alirocumab on Postprandial Hyperlipemia in Patients With Type 2 Diabetes

• Status: Recruiting
• Trial end date: 2022-04-30
• Target enrollment: 0
• Participant gender: Male

Summary

Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged over the past decade as a post-transcriptional regulator of the LDL receptor (LDL-R). PCSK9 acts as an endogenous natural inhibitor of the LDL-R pathway. Monoclonal antibodies (mAb) directed against PCSK9, such as Alirocumab, are the most common method of PCSK9 inhibition.

The goal of the present study is to assess, in the context of type 2 diabetes, a situation associated with an increased post-prandial hyperlipemia, whether PCSK9 inhibition with Alirocumab affects postprandial intestinal lipoprotein metabolism.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Nantes University Hospital
• Collaborator: Regeneron Pharmaceuticals
• Treatments: Antibodies, Monoclonal

Criteria

Inclusion Criteria:

• Men with type 2 diabetes diagnosed since ≥ 6 months

• HbA1C <9.0%

• Men with primary hypercholesterolemia and/or mixed dyslipidemia

• Aged 18-75 years (limits inclusive)

• Patient could be treated for type 2 diabetes when diet and physical activity are not sufficient to restore glycemic control. The treatment must be stable 1 month before the inclusion and have to remain unchanged all along the study. The only authorized treatments are:

• Metformin

• And/or Sulphonylureas (SUs)

• And/or Repaglinide

• And/or DPP-4 inhibitors

• And/or GLP1 receptor agonists: exenatide, liraglutide, dulaglutide

• Fasting serum TG ≥ 150 mg/dl and < 500 mg/dl

• BMI: 20-45 kg/m2

• Use of statins or ezetimibe is allowed if treatment is stable for ≥ 1 month before the screening

Exclusion Criteria:

• Any secondary causes of hypercholesterolemia or of mixed dyslipidemia (nephrotic syndrome, hypothyroidism…)

• impaired liver function (AST and/or ALT ≥ 3ULN)

• impaired renal function (eGFR with CKD-EPI formula < 30 ml/min)

• Alcohol abuse (> 2 standard alcoholic drink per day; 1 standard alcoholic drink is the equivalent of 10g of alcohol)

• History of myocardial infarction, acute coronary syndrome, unstable angina pectoris, stroke, transient ischemic attack, or cardiac revascularization within the 6 months before the screening visit.

• History of PCSK9 mAb use

• Known sensitivity to monoclonal antibody therapeutics or to their excipients

• Lipid lowering therapies (other than statins), including fibrates, omega-3 fatty acids, bile acid sequestrants, niacin.

• Insulin-treated patients

• History of bariatric surgery

• Inflammatory bowel diseases and gastrointestinal malabsorption diseases

• Uncontrolled hypothyroidism (TSH > ULN and Free T4 < ULN) or hyperthyroidism (TSH < ULN)

• Active cancer: progressive cancer or remission ≤ 3 years, except for basal or squamous cell carcinoma of the skin that has been successfully treated

• Known history of positive test for HIV, hepatitis C or chronic hepatitis B

• Corticosteroids therapy

• Minors

• Adults under guardianship or trusteeship