- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03374358
Effect on Liver Fat and Metabolic Parameters When Switching a Protease Inhibitor or Efavirenz to Raltegravir (OBERAL)
Effect on Liver Fat, Adipose Tissue and Metabolic Parameters When Switching a Protease Inhibitor or Efavirenz to Once Daily Raltegravir in HIV+ Patients With Body Mass Index Over 25 kg/m2 and With at Least One Metabolic Syndrome Component
This study will provide data on the switch from a protease inhibitor or efavirenz to the new formulation of raltegravir (RAL) dosed once daily. The study group consists of patients with metabolic risk factors and co-morbidities, in need of optimization of their current ART to minimize the drug-related metabolic side effects as standard of care.
The primary objective of this study is to investigate whether switching a protease inhibitor (PI) or efavirenz to raltegravir once daily reduces liver fat in patients who are overweight or obese and have at least one metabolic syndrome component. For this purpose, the liver fat content will be analyzed using the proton magnetic resonance spectroscopy.
In addition, the aim is to clarify the change in the body composition and metabolism in this study group. For this purpose the visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) volumes will be measured and subcutaneous tissue samples will be collected for future analyses of adipose tissue function.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The prevalences of overweight (body-mass-index, BMI 25-30 kg/m2) and obesity (BMI>30 kg/m2) are steadily increasing among HIV-infected patients globally. In parallel, the risk of non-alcoholic fatty liver disease (NAFLD) increases. Clinically alarming are the data which suggest that HIV infected have higher rates of progressive form of NAFLD than non-HIV infected age, gender and BMI matched controls.
As the treatment for HIV is life-long, it is crucial to understand the effects of different antiretroviral therapy (ART) regimens on metabolism. Some antiretroviral agents appear to promote unfavourable changes in metabolism (e.g. in blood lipids) and predispose to trunk fat redistribution and liver fat accumulation.
Raltegravir has been demonstrated to have beneficial impact on some metabolic parameters compared to the protease inhibitor class or efavirenz. In this study, the aim is to investigate whether switching a protease inhibitor or efavirenz to raltegravir reduces liver fat in patients who are overweight or obese and have at least one metabolic syndrome component. For this purpose, the proton magnetic resonance spectroscopy will be used.
In addition, the aim is to clarify the change in the body composition in this study group. For this purpose, the visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) volumes will be measured using MRI.
To acquire more knowledge on metabolic effects in adipose tissue level, subcutaneous adipose tissue biopsies will be collected together with blood, saliva and feces samples.
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
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Helsinki, Finland
- Aurora hospital, Department of Infectious Diseases
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Written informed consent (IC) obtained.
- HIV-positive adult (age over 18) subjects currently on stable ART, with no changes in the ART regimens during the past 6 months.
- Current ART includes either a protease inhibitor or efavirenz.
- No documented or suspected resistance to integrase inhibitors or to NRTIs.
- No prior history of virologic failure. Failure is defined as a confirmed plasma viral load > 200 cop/ml measured no less than six months after initiation or modification of therapy.
- Virological blips accepted only if a single viral load measurement has been between 50-200 cop/ml followed by viral load < 50 cop/ml without the need to initiate a change in ART and no blip within 12 month window period prior to screening.
- Documented evidence of at least two HIV viral load < 50 cop/ml measurements during the past 12 months prior to inclusion: one within 6 months prior to screening.
- HIV viral load < 50 cop/ml at screening.
BMI>25 kg/m2 and one metabolic syndrome condition, which are
- BP ≥ 130/≥ 85 mmHg or hypertension medication currently in use or
- fasting glucose ≥ 5.6 mmol/l or B-HbA1C > 42 mmol/mol or diabetes medication currently in use or
- HDL < 1.0 mmol/l in men and < 1.3 mmol/l in women or triglycerides ≥ 1.7 mmol/l or a cholesterol-lowering regimen currently in use or
- waist circumference > 94 cm in men and >80 cm in women (or respective cut off values for non-European ethnic groups as defined by International Diabetes Federation). OR
- ultrasound or biopsy proven hepatosteatosis.
Exclusion Criteria:
- Within 12 month window period prior to screening, HIV viral load measurement of >50 cop/ml.
- More than one consecutive HIV viral load measurements of > 50 cop/ml in the treatment history after initial viral suppression with ART.
- Chronic hepatitis B or C.
- Daily alcohol consumption ≥ 30 g for men and ≥ 20 g for women.
- Pregnancy or planned pregnancy during the study period.
- Lipid or glucose lowering regimen or hormonal supplement started within 3 months before the planned study start.
- Psychiatric disorder, which prevents a study subject to understand the study protocol.
- Other serious disease, which prevents a study subject to participate in the study.
- For MRI/spectroscopy imaging: metal objects in the body or claustrophobia.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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NO_INTERVENTION: No intervention arm.
Study subjects will continue their current antiretroviral regimens, which include a protease inhibitor or efavirenz plus two nucleoside analog reverse-transcriptase inhibitors (NRTIs).
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EXPERIMENTAL: Raltegravir arm.
Study subjects will switch their protease inhibitor or efavirenz to once daily raltegravir plus continue current nucleoside analog reverse-transcriptase inhibitors (NRTIs).
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The aim of this study is to investigate whether switching a protease inhibitor (PI) or efavirenz to raltegravir has effect on liver fat and metabolism in HIV-infected patients who are overweight or obese and have at least one metabolic syndrome component .
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Liver Fat
Time Frame: Baseline and 24 weeks
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24 week value minus baseline value, liver fat % measured by proton magnetic resonance spectroscopy.
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Baseline and 24 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Subcutaneous and Visceral Adipose Tissue Volume
Time Frame: Baseline and 24 weeks
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24 week value minus baseline value: change in subcutaneous (SAT) and visceral (VAT) adipose tissue volume (mL) measured by magnetic resonance imaging.
Analysis included a series of T1-weighted trans-axial images from 8 cm above to 8 cm below the 4th and 5th lumbar intervertebral disc (16 slices, field of view 375 x 500 mm2, slice thickness 10 mm).
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Baseline and 24 weeks
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Change in Body Weight and Total Body Fat
Time Frame: Baseline and 24 weeks
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24 week value minus baseline value, change in body weight (kg) and total body fat (kg) measured by Bioelectrical Impedance Analysis.
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Baseline and 24 weeks
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Liver Stiffness
Time Frame: Baseline and 24 weeks
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24 week minus baseline value, change in liver stiffness (kPa) measured by transient elastography (Fibroscan ®).
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Baseline and 24 weeks
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Change in Fasting Plasma Glucose
Time Frame: Baseline and 24 weeks
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24 week value minus baseline value, change in fasting plasma glucose (mg/dL).
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Baseline and 24 weeks
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Change in Fasting Serum Lipid Profile
Time Frame: Baseline and 24 weeks
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24 week value minus baseline value, change in fasting serum lipid profile: LDL and HDL cholesterol, triglyceride (all values in mmol/L)
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Baseline and 24 weeks
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Change in Metabolic and Inflammatory Biomarkers: hsCRP
Time Frame: Baseline and 24 weeks
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24 week value minus baseline value, change in circulating metabolic and inflammatory biomarkers: high sensitivity C-reactive protein (hsCRP mg/L)
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Baseline and 24 weeks
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Change in Metabolic and Inflammatory Biomarkers: IL-6
Time Frame: Baseline and 24 weeks
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24 week value minus baseline value, change in circulating metabolic and inflammatory biomarkers: interleukin 6 (IL-6 pg/mL)
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Baseline and 24 weeks
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Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Jussi Sutinen, MD PhD, Helsinki University Central Hospital
Publications and helpful links
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Pathologic Processes
- Glucose Metabolism Disorders
- Metabolic Diseases
- RNA Virus Infections
- Virus Diseases
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Sexually Transmitted Diseases, Viral
- Sexually Transmitted Diseases
- Lentivirus Infections
- Retroviridae Infections
- Immunologic Deficiency Syndromes
- Immune System Diseases
- Disease
- Liver Diseases
- Insulin Resistance
- Hyperinsulinism
- HIV Infections
- Syndrome
- Fatty Liver
- Metabolic Syndrome
- HIV Seropositivity
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Anti-HIV Agents
- Anti-Retroviral Agents
- HIV Integrase Inhibitors
- Integrase Inhibitors
- Raltegravir Potassium
Other Study ID Numbers
- OBERAL
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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