Acetyl-L-Carnitine in Type 2 Diabetes (DIABASI)
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.
|Diabetes Type 2 Hypertension||Drug: acetyl-L-carnitine/statin (simvastatin) Drug: placebo||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|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|
- Arterial blood pressure and dyslipidemia [ Time Frame: Basal, 15th day, 30th day, 3rd and 6th month ]
|Study Start Date:||April 2008|
|Study Completion Date:||December 2012|
|Primary Completion Date:||May 2012 (Final data collection date for primary outcome measure)|
Statin and acetyl-L-carnitine
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
Placebo Comparator: 2
Statin and placebo
placebo: 4 tablets of 500 mg a day simvastatin: 10 to 20 mg/day as deemed clinically appropriate and according to tolerability
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT00984750
|Hospital "Azienda Ospedaliera di Treviglio e Caravaggio" Ambulatory of Diabetology|
|Ponte San Pietro, Bergamo, Italy, 24036|
|Clinical Research Center for Rare Diseases "Aldo and Cele Daccò"|
|Ranica, Bergamo, Italy, 24020|
|Hospital "Azienda Ospedaliera di Treviglio-Caravaggio"Unit of Diabetology and Metabolic Diseases|
|Romano di Lombardia, Bergamo, Italy|
|Hospital "Azienda Ospedaliera di Treviglio-Caravaggio" Unit of Diabetology and Metabolic Disease|
|Treviglio, Bergamo, Italy|
|Hospital "Azienda Ospedaliera Ospedali Riunitidi Bergamo" Unit of Diabetology|
|Bergamo, Italy, 24100|
|Study Director:||Piero Ruggenenti, MD||Mario Negri Institute for Pharmacological Research|