Raltegravir Insulin Sensitivity Study - Full Text View

Purpose

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).

Condition	Intervention	Phase
HIV Infections	Drug: Raltegravir then lopinavir/ritonavir Drug: Lopinavir/ritonavir then raltegravir	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacodynamics Study Intervention Model: Parallel Assignment Masking: Open Label
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.

Resource links provided by NLM:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: Diabetes Medicines HIV/AIDS

Drug Information available for: Ritonavir Lopinavir Raltegravir Raltegravir potassium

U.S. FDA Resources

Further study details as provided by St Stephens Aids Trust:

Primary Outcome Measures:

Change from baseline in insulin sensitivity by euglycaemic clamp method [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Change from baseline in serum levels of fasting cholesterol, triglycerides [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]

Enrollment:	18
Study Start Date:	October 2007
Study Completion Date:	August 2008
Primary Completion Date:	August 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

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

Ages Eligible for Study:	18 Years to 60 Years
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	Yes

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00531999

Locations

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

Sponsors and Collaborators

St Stephens Aids Trust

Investigators

Principal Investigator:

Greame Moyle

Chelsea & Westminser Healthcare NHS Trust

More Information

No publications provided

Responsible Party:	Dr Graeme Moyle, St Stephen's AIDS Trust
ClinicalTrials.gov Identifier:	NCT00531999 History of Changes
Other Study ID Numbers:	SSAT023
Study First Received:	September 18, 2007
Last Updated:	August 13, 2010
Health Authority:	United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by St Stephens Aids Trust:

Raltegravir
Euglycaemic clamp
healthy volunteer

Additional relevant MeSH terms:

HIV Infections
Acquired Immunodeficiency Syndrome
Insulin Resistance
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Hyperinsulinism
Glucose Metabolism Disorders

Metabolic Diseases
Ritonavir
Lopinavir
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on March 07, 2013