Raltegravir Insulin Sensitivity Study

An Open Label Study of the Impact on Insulin Sensitivity, Lipid Profile and Vascular Inflammation by Treatment With Lopinavir / Ritonavir (400 / 100 mg Twice Daily) or Raltegravir 400 mg Twice Daily in HIV Negative Male Volunteers.

The purpose of the study is to look at the effects of two different HIV medications on the body's response to insulin (a hormone that regulates blood sugar levels). This will be done using a method called the 'euglycaemic clamp'

The study will also investigate the effects of these drugs on blood fats and on circulating markers in the blood stream related to blood vessels (vascular inflammation markers).

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Raltegravir then lopinavir/ritonavir; Drug: Lopinavir/ritonavir then raltegravir

Detailed Description

Subjects will undergo four euglycaemic clamp procedures in order to determine the extent of glucose disposal. The first clamp will be performed prior to the commencement of the first study drug administration, the second one following two weeks of study drug, the third after a two week washout period, prior to commencement of second study drug administration and the fourth after two weeks of the second study drug

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom
    • St Stephens Centre, Chelsea & Westminster Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Subjects must have documented negative HIV serology by ELISA and P24 antigen
• Subjects must be clinically well males aged between 18 to 60 years
• Fasting blood glucose, total cholesterol and triglycerides within normal limits
• Hepatic transaminases (AST and ALT) ≤ 3 × upper limit of normal (ULN)
• Adequate hematologic function (absolute neutrophil count ≥ 1,000/mm3; platelets ≥ 50,000/mm3; hemoglobin ≥ 8.0 g/dL)
• Serum amylase ≤ 1.5 × ULN (subjects with serum amylase > 1.5 × ULN will remain eligible if pancreatic lipase is ≤ 1.5 × ULN)
• Sexually active males must use condoms during the course of the study
• Life expectancy ≥ 1 year
• Willing and able to provide informed consent

Exclusion Criteria:

• Subjects with a waist hip ratio > 0.97 or BMI > 28 kg/m2 will be excluded
• Acute or chronic hepatitis B infection (determined by positive hepatitis B surface antigen result at the screening visit)
• Acute or chronic hepatitis C infection (determined by positive hepatitis C antibody result at the screening visit)
• Other metabolic syndrome or disease process in the opinion of the investigator likely to cause marked disturbance in glucose and lipid homeostasis including hypertension

• Receiving on-going therapy with any of the following:

  • Metabolically active medications
  • Any lipid-lowering medication
  • Hormonal agents (oestrogens or androgens)
  • Glucocorticoids
  • Beta-blockers
  • Thiazide diuretics
  • Thyroid preparations
  • Psychotropic agents
  • Anabolic steroids
  • Megestrol acetate

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; Raltegravir 400 mg twice daily for the first 14 days of the study. Lopinavir/ritonavir 400/100 mg twice daily for the last 14 days of the study	Drug: Raltegravir then lopinavir/ritonavir; raltegravir 400mg twice daily for first 14 days of study lopinavir/ritonavir 400/100mg twice daily for last 14 days of study
Active Comparator: 2; Lopinavir/ritonavir 400/100 mg twice daily for the first 14 days of the study.; Raltegravir 400 mg twice daily for the last 14 days of the study.	Drug: Lopinavir/ritonavir then raltegravir; lopinavir/ritonavir 400 mg twice daily for the first 14 days of the study raltegravir 400mg twice daily for the last 14 days of the study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in insulin sensitivity by euglycaemic clamp method	2 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in serum levels of fasting cholesterol, triglycerides	2 weeks

Collaborators and Investigators

• Sponsor: St Stephens Aids Trust
• Investigators: Principal Investigator: Greame Moyle, Chelsea & Westminser Healthcare NHS Trust

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): August 1, 2008
• Study Completion (Actual): August 1, 2008

Study Registration Dates

• First Submitted: September 18, 2007
• First Submitted That Met QC Criteria: September 18, 2007
• First Posted (Estimate): September 19, 2007

Study Record Updates

• Last Update Posted (Estimate): August 16, 2010
• Last Update Submitted That Met QC Criteria: August 13, 2010
• Last Verified: August 1, 2010

More Information

Terms related to this study

• Keywords: healthy volunteer; Raltegravir; Euglycaemic clamp
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperinsulinism; Insulin Resistance; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Integrase Inhibitors; Integrase Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Raltegravir Potassium; Ritonavir; Lopinavir
• Other Study ID Numbers: SSAT023