Clinical trial NCT00531999: Raltegravir Insulin Sensitivity Study
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Keywords: Raltegravir
Euglycaemic clamp
healthy volunteer
Lead sponsor: St Stephens Aids Trust
Sponsor class: OTHER
First posted: 2007-09-19
Enrollment: 18
Sex: MALE
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL

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

Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline in insulin sensitivity by euglycaemic clamp method
timeFrame: 2 weeks
Secondary outcomes:
measure: Change from baseline in serum levels of fasting cholesterol, triglycerides
timeFrame: 2 weeks
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: St Stephens Centre, Chelsea & Westminster Hospital
Study officials:
affiliation: Chelsea & Westminser Healthcare NHS Trust
name: Greame Moyle
role: PRINCIPAL_INVESTIGATOR
References: