Acetyl-L-Carnitine in Type 2 Diabetes

• Status: Completed
• Trial end date: 2012-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Decreased insulin sensitivity (or insulin resistance) is a major risk factor for type 2 diabetes mellitus and renal and cardiovascular disease. It is the key component and, possibly, a pathogenetic factor of the metabolic syndrome - a clustering of arterial hypertension, obesity, impaired glucose tolerance, dyslipidemia, coagulation abnormalities, albuminuria and increased cardiovascular risk - that may precede or accompany type 2 diabetes.

Insulin function and the abnormalities associated with insulin resistance, may have a major role in preventing type 2 diabetes and, in the long-term, diabetes micro- and macrovascular complications. Carnitine is involved in lipids and carbohydrates metabolism and acetyl-L-carnitine (ALC), an intramitochondrial carrier of acylic group, may modulate cell fuel substrate utilization. Studies found that carnitine may improve insulin sensitivity and glucose disposal in healthy subjects and in patients with type 2 diabetes. A recent study found that a primed constant infusion of acetyl-L-carnitine (ALC) may increase glucose utilization in type 2 diabetic patients, possibly restoring the glycogen synthase activity.

In a previous pilot study in healthy subjects with decreased insulin sensitivity, the investigators found that 6-month treatment with Acetyl-L-Carnitine - an ester of l-carnitine

• improved the glucose disposal rate, taken as a marker of insulin sensitivity. Amelioration of insulin sensitivity was associated with a significant and clinically relevant reduction in systolic blood pressure without appreciable changes in diastolic blood pressure. Whether blood pressure reduction reflected the amelioration of insulin sensitivity or, rather, a direct, specific effect of Acetyl-L-Carnitine is still unknown.The antihypertensive effect ensued progressively and slowly waned after treatment withdrawal as documented by a slow and progressive increase in blood pressure levels toward baseline levels over the recovery period. This finding provided convincing evidence that blood pressure reduction throughout the observation period was not explained by a "trial effect", but reflected a true treatment effect. Blood pressure was a secondary efficacy variable of the study and mechanisms underlying the antihypertensive effect of Acetyl-L-Carnitine (such as reduced peripheral resistances, decreased cardiac output, increased artery compliance and/or enhanced sodium excretion), in this population were not assessed.

Acetyl-L-Carnitine was well tolerated in all of the patients and may provide a novel therapeutic tool for the treatment of arterial hypertension, and of dyslipidemia and could be safely used in people with type 2 diabetes.

Thus, the investigators designed a prospective, randomized, double-blind, placebo-controlled trial to investigate whether Acetyl-L-Carnitine added-on stable and standardized blood pressure and lipid lowering therapy may help further improving control of hypertension and dyslipidemia and, therefore, decreasing the overall cardiovascular risk in hypertensive patients with type 2 diabetes.

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

Details

• Lead Sponsor: Mario Negri Institute for Pharmacological Research
• Collaborators: Leadiant Biosciences, Inc.; Sigma Tau Pharmaceuticals, Inc.
• Treatments: Acetylcarnitine; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Simvastatin

Criteria

Inclusion Criteria:

• Males and females >40 years old;

• High-risk subjects with type 2 diabetes (WHO criteria);

• High blood pressure (systolic blood pressure >140 mmHg or with concomitant antihypertensive treatment stable since at least 3 months);

• Serum creatinine concentration <1.5 mg/dl;

• Patients legally able to give written informed consent to the trial (signed and dated by the patient);

• Written informed consent.

Exclusion criteria:

• Uncontrolled diabetes (glycated hemoglobin >11%);

• Acute cardiovascular events over the last 3 months;

• Specific contraindications or history of hypersensitivity to the study drugs;

• Previous history of allergy or intolerance, or evidence of immunologically-mediated renal disease, systemic diseases, cancer;

• Drug or alcohol abuse;

• Any chronic clinical conditions that may affect completion of the trial or confound data interpretation;

• Pregnancy or lactating;

• Women of childbearing potential without following a scientifically accepted form of contraception;

• Legal incapacity and/or other circumstances rendering the patient unable to understand the nature, scope and possible consequence of the trial;

• Evidence of an uncooperative attitude;

• Any evidence that patient will not be able to complete the trial follow-up.