Clinical trial NCT00984750: Acetyl-L-Carnitine in Type 2 Diabetes
Official title: A Prospective, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Effect of 6-month Acetylcarnitine Therapy on Arterial Blood Pressure, Lipid and Metabolic Profile, and Kidney Function in Hypertensive Patients With Type 2 Diabetes on Background Simvastatin Therapy
Conditions: Diabetes Type 2
Hypertension
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.
Interventions:
description: acetyl-L-carnitine: 4 tablets of 500 mg a day<br/>simvastatin: 10 to 20 mg/day as deemed clinically appropriate and according to tolerability
name: acetyl-L-carnitine/statin (simvastatin)
type: Drug
description: placebo: 4 tablets of 500 mg a day simvastatin: 10 to 20 mg/day as deemed clinically appropriate and according to tolerability
name: placebo
type: Drug
Study arms:
design_group_description: Statin and acetyl-L-carnitine
design_group_title: 1
design_group_type: Experimental
design_group_description: Statin and placebo
design_group_title: 2
design_group_type: Placebo Comparator
Sponsor: Istituto di Ricerche Farmacologiche Mario Negri
Collaborators: Leadiant Biosciences, Inc.
Drug name mappings:
name: 辛伐他汀
lang: CN
name: Simvastatin
lang: EN
name: シンバスタチン
lang: JP
name: 乙酰左旋肉碱
lang: CN
name: Acetyl-L-carnitine
lang: EN