Raltegravir Insulin Sensitivity Study

Phase 1

Completed

• Conditions: HIV Infections
• Interventions: Drug: Raltegravir then lopinavir/ritonavir; Drug: Lopinavir/ritonavir then raltegravir

• Registration Number: NCT00531999
• Lead Sponsor: St Stephens Aids Trust

Brief Summary

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).

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 Timeline

• Study First Submitted: 2007-09-18
• Study First Submitted QC: 2007-09-18
• Study First Posted: 2007-09-19
• Study Start: 2007-10
• Primary Completion: 2008-08
• Study Completion: 2008-08
• Status Verified: 2010-08
• Last Update Submitted: 2010-08-13
• Last Update Posted: 2010-08-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 18

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	Raltegravir then lopinavir/ritonavir	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
2	Lopinavir/ritonavir then raltegravir	* 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.

Primary Outcome Measures

Name	Time	Method
Change from baseline in insulin sensitivity by euglycaemic clamp method	2 weeks

Secondary Outcome Measures

Name	Time	Method
Change from baseline in serum levels of fasting cholesterol, triglycerides	2 weeks

Trial Locations

Locations (1)

St Stephens Centre, Chelsea & Westminster Hospital; 🇬🇧 London, United Kingdom