Acetyl-L-Carnitine in Type 2 Diabetes

NCT00984750 | Completed Phase 3

• 2 other identifiers: DIABASI2007-005925-31
• Study Type: interventional
• Target: 229
• Locations: 1 country
• Sites: 5

Brief 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

Outcome Measures

Primary Outcomes (1)

• Arterial blood pressure and dyslipidemia

  Basal, 15th day, 30th day, 3rd and 6th month

Study Arms (2)

1

EXPERIMENTAL

Statin and acetyl-L-carnitine

Drug: acetyl-L-carnitine/statin (simvastatin)

2

PLACEBO COMPARATOR

Statin and placebo

Drug: placebo

Interventions

acetyl-L-carnitine/statin (simvastatin) DRUG

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

1

placebo DRUG

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

2

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mario Negri Institute for Pharmacological Research: lead
• Leadiant Biosciences, Inc.: collaborator

Study Sites (5)

Hospital "Azienda Ospedaliera Ospedali Riunitidi Bergamo" Unit of Diabetology

Bergamo, Bergamo, 24100, Italy

Location

Hospital "Azienda Ospedaliera di Treviglio e Caravaggio" Ambulatory of Diabetology

Ponte San Pietro, Bergamo, 24036, Italy

Location

Clinical Research Center for Rare Diseases "Aldo and Cele Daccò"

Ranica, Bergamo, 24020, Italy

Location

Hospital "Azienda Ospedaliera di Treviglio-Caravaggio"Unit of Diabetology and Metabolic Diseases

Romano di Lombardia, Bergamo, Italy

Location

Hospital "Azienda Ospedaliera di Treviglio-Caravaggio" Unit of Diabetology and Metabolic Disease

Treviglio, Bergamo, Italy

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Hypertension

Interventions

Acetylcarnitine; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Simvastatin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Carnitine; Trimethyl Ammonium Compounds; Quaternary Ammonium Compounds; Amines; Organic Chemicals; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Enzyme Inhibitors; Lipid Regulating Agents; Therapeutic Uses; Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Study Officials

• Piero Ruggenenti, MD

  Mario Negri Institute for Pharmacological Research

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2009
• First Posted: September 25, 2009
• Study Start: April 1, 2008
• Primary Completion: May 1, 2012
• Study Completion: December 1, 2012
• Last Updated: February 25, 2013

Record last verified: 2013-02

Locations

IT (5)