Acetyl-L-Carnitine in Type 2 Diabetes

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.

Conditions

• Diabetes Type 2
• Hypertension

Interventions

DRUG

acetyl-L-carnitine/statin (simvastatin)

acetyl-L-carnitine: 4 tablets of 500 mg a day simvastatin: 10 to 20 mg/day as deemed clinically appropriate and according to tolerability

DRUG

placebo

placebo: 4 tablets of 500 mg a day simvastatin: 10 to 20 mg/day as deemed clinically appropriate and according to tolerability

Sponsors & Collaborators

• Leadiant Biosciences, Inc.

  collaborator INDUSTRY

• Mario Negri Institute for Pharmacological Research

  lead OTHER

Principal Investigators

• Piero Ruggenenti, MD · Mario Negri Institute for Pharmacological Research

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

40 Years

Max Age

85 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2008-04-30

Primary Completion

2012-05-31

Completion

2012-12-31

Countries

• Italy

Study Locations