Acipimox to Improve Hyperlipidemia and Insulin Sensitivity Associated With HIV
Summary
The purpose of this study is to test whether chronic administration of the drug acipimox will improve hyperlipidemia and insulin sensitivity among HIV infected patients experiencing highly active antiretroviral therapy (HAART) associated metabolic disturbances.
Description
BACKGROUND:
HIV infected patients treated with HAART are at increased risk for developing significant dyslipidemia, insulin resistance, and abnormal patterns of fat distribution. While the exact mechanism responsible for these changes is not known, there is increasing evidence that patients with HIV infection and fat redistribution have increased basal rates of lipolysis and elevated circulating free fatty acids (FFA). Patients with HIV associated lipodystrophy have increased FFA levels that correlated directly with impaired glucose metabolism and triglyceride concentrations. Furthermore, acute inhibition of lipolysis in patients with HIV lipodystrophy and insulin resistance results in improvement in insulin sensitivity. However, long-term administration of lipolytic blocking agents has not been evaluated in this patient population. Acipimox, a nicotinic acid analogue and a potent inhibitor of lipolysis, is an established therapy for dyslipidemia. In addition, through effects on lowering circulating FFA, acute administration of acipimox has been shown to improve insulin sensitivity in other populations, including lean and obese individuals and patients with type II diabetes. This study will test the hypothesis that chronic administration of acipimox will improve hyperlipidemia and insulin sensitivity among HIV infected patients experiencing HAART associated metabolic disturbances.
DESIGN NARRATIVE:
The study will be a 3-month double-blind placebo-controlled trial of 250 mg of acipimox three times daily in 30 patients with HAART lipodystrophy. The primary clinical endpoint of this study will be the change in fasting triglyceride concentration, comparing baseline values to those obtained after 3 months of acipimox or placebo. Insulin sensitivity, an important secondary endpoint, will be determined by hyperinsulinemic euglycemic clamp studies. Rates of lipolysis in the fasting state will be quantified by a 3-hour infusion of stable isotope-labeled glycerol. Indirect calorimetry will be used to assess changes in resting energy expenditure. Cross-sectional computed tomography (CT) imaging of the thigh and abdomen will allow for measurement of visceral and subcutaneous fat areas. Dual energy x-ray absorptiometry (DEXA) will be used to determine whole body fat mass.
Study Design
Allocation: Randomized, Control: Placebo Control, Masking: Double-Blind, Primary Purpose: Prevention
Conditions
Insulin Resistance
Intervention
Acipimox
Location
Massachusetts General Hospital
Boston
Massachusetts
United States
02114
Status
Completed
Source
National Heart, Lung, and Blood Institute (NHLBI)
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00246402
- Information obtained from ClinicalTrials.gov on July 15, 2010
Published on BioPortfolio: 2014-08-27T03:47:57-0400
Clinical Trials
The Effect of Acipimox on GLP (Glucagon-like Peptide)-1 Secretion
Glucagon like peptide 1 is produced in enteroendocrine L cells in the small intestine stimulated by peroral food intake. GLP-1 induces insulin secretion, and analogues are used in the trea...
Effect of 4 Weeks Treatment With Acipimox in Patients With Chronic Heart Failure
The primary objective of this study is to evaluate whether metabolic modulation improves left ventricular function, work capacity, insulin sensitivity and modifies substrate metabolism in ...
GH-PP-Ghrelin Loop and Sympathicolysis in Bulimia
This study evaluates the addition of Acipimox or placebo to exercise on growth hormone release and ghrelin secretion in bulimic patients and in healthy women. Two groups of participants wi...
Accumulation of lipid in skeletal and cardiac muscle has been associated with insulin resistance and diabetic cardiomyopathy. In skeletal muscle, lipotoxic damage has been suggested to lea...
Lipolytic Effects of GH in Hypopituitary Patients in Vivo
Growth hormone (GH) is essential for longitudinal bone growth and somatic development. These protein anabolic effects require sufficient nutritional supply. During fasting and caloric rest...
PubMed Articles
Insulin resistance, defined as attenuated sensitivity responding to insulin, impairs insulin action. Direct causes and molecular mechanisms of insulin resistance have thus far remained elusive. Here w...
Insulin Resistance and the Risk of Diabetes and Dysglycemia in Korean General Adult Population.
Insulin resistance is a major pathogenic hallmark of impaired glucose metabolism. We assessed the accuracy of insulin resistance and cut-off values using homeostasis model assessment of insulin resist...
A reduction in insulin-stimulated glucose uptake in skeletal muscles is a characteristic of insulin resistance and type 2 diabetes mellitus (T2DM). The glucagon-like peptide (GLP)-1 agonist liraglutid...
Global Analyses of Selective Insulin Resistance in Hepatocytes due to Palmitate Lipotoxicity.
Obesity is tightly linked to hepatic steatosis and insulin resistance. One feature of this association is the paradox of selective insulin resistance: insulin fails to suppress hepatic gluconeogenesis...
Prenatal Testosterone Programming of Insulin Resistance in the Female Sheep.
Insulin resistance, a common feature of metabolic disorders such as obesity, nonalcoholic fatty liver disease, metabolic syndrome, and polycystic ovary syndrome, is a risk factor for development of di...
Medical and Biotech [MESH] Definitions
Hyperinsulinism
A syndrome with excessively high INSULIN levels in the BLOOD. It may cause HYPOGLYCEMIA. Etiology of hyperinsulinism varies, including hypersecretion of a beta cell tumor (INSULINOMA); autoantibodies against insulin (INSULIN ANTIBODIES); defective insulin receptor (INSULIN RESISTANCE); or overuse of exogenous insulin or HYPOGLYCEMIC AGENTS.
Insulin Resistance
Diminished effectiveness of INSULIN in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent HYPERGLYCEMIA or KETOSIS. It can be caused by the presence of INSULIN ANTIBODIES or the abnormalities in insulin receptors (RECEPTOR, INSULIN) on target cell surfaces. It is often associated with OBESITY; DIABETIC KETOACIDOSIS; INFECTION; and certain rare conditions. (from Stedman, 25th ed)
Thiazolidinediones
THIAZOLES with two keto oxygens. Members are insulin-sensitizing agents which overcome INSULIN RESISTANCE by activation of the peroxisome proliferator activated receptor gamma (PPAR-gamma).
Donohue Syndrome
Rare autosomal recessive syndrome of extreme insulin resistance due to mutations in the binding domain of INSULIN RECEPTOR. Clinical features include severe intrauterine and postnatal growth restriction, characteristic dysmorphic FACIES; HIRSUTISM; VIRILIZATION; multiple endocrine abnormalities, and early death.
Biphasic Insulins
An insulin preparation that is designed to provide immediate and long term glycemic control in a single dosage. Biphasic insulin typically contains a mixture of REGULAR INSULIN or SHORT-ACTING INSULIN combined with a LONG-ACTING INSULIN.
