Back to results

Effect on Liver Fat and Metabolic Parameters When Switching a Protease Inhibitor or Efavirenz to Raltegravir (OBERAL)

Primary Purpose

HIV Seropositivity, Metabolic Syndrome, Fatty Liver

Status

Completed

Phase

Phase 4

Locations

Finland

Study Type

Interventional

Intervention

Raltegravir

About this trial

This is an interventional treatment trial for HIV Seropositivity

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Aurora hospital, Department of Infectious Diseases

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Experimental

Arm Label

No intervention arm.

Raltegravir arm.

Arm Description

Study subjects will continue their current antiretroviral regimens, which include a protease inhibitor or efavirenz plus two nucleoside analog reverse-transcriptase inhibitors (NRTIs).

Study subjects will switch their protease inhibitor or efavirenz to once daily raltegravir plus continue current nucleoside analog reverse-transcriptase inhibitors (NRTIs).

Outcomes

Primary Outcome Measures

Change in Liver Fat

24 week value minus baseline value, liver fat % measured by proton magnetic resonance spectroscopy.

Secondary Outcome Measures

Change in Subcutaneous and Visceral Adipose Tissue Volume

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).

Change in Body Weight and Total Body Fat

24 week value minus baseline value, change in body weight (kg) and total body fat (kg) measured by Bioelectrical Impedance Analysis.

Full Information

NCT ID

NCT03374358

First Posted

December 2, 2017

Last Updated

August 9, 2021

Sponsor

Helsinki University Central Hospital

Collaborators

Merck Sharp & Dohme LLC

1. Study Identification

Unique Protocol Identification Number

NCT03374358

Brief Title

Effect on Liver Fat and Metabolic Parameters When Switching a Protease Inhibitor or Efavirenz to Raltegravir

Acronym

OBERAL

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2021

Overall Recruitment Status

Completed

Study Start Date

January 10, 2018 (Actual)

Primary Completion Date

November 2, 2019 (Actual)

Study Completion Date

November 30, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Helsinki University Central Hospital

Collaborators

Merck Sharp & Dohme LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HIV Seropositivity, Metabolic Syndrome, Fatty Liver

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Model Description

This study is a randomized, open, parallel design study.

Masking

None (Open Label)

Allocation

Randomized

Enrollment

45 (Actual)

8. Arms, Groups, and Interventions

Arm Title

No intervention arm.

Arm Type

No Intervention

Arm Description

Study subjects will continue their current antiretroviral regimens, which include a protease inhibitor or efavirenz plus two nucleoside analog reverse-transcriptase inhibitors (NRTIs).

Arm Title

Raltegravir arm.

Arm Type

Experimental

Arm Description

Study subjects will switch their protease inhibitor or efavirenz to once daily raltegravir plus continue current nucleoside analog reverse-transcriptase inhibitors (NRTIs).

Intervention Type

Drug

Intervention Name(s)

Raltegravir

Other Intervention Name(s)

Isentress

Intervention Description

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 .

Primary Outcome Measure Information:

Title

Change in Liver Fat

Description

24 week value minus baseline value, liver fat % measured by proton magnetic resonance spectroscopy.

Time Frame

Baseline and 24 weeks

Secondary Outcome Measure Information:

Title

Change in Subcutaneous and Visceral Adipose Tissue Volume

Description

Time Frame

Baseline and 24 weeks

Title

Change in Body Weight and Total Body Fat

Description

24 week value minus baseline value, change in body weight (kg) and total body fat (kg) measured by Bioelectrical Impedance Analysis.

Time Frame

Baseline and 24 weeks

Other Pre-specified Outcome Measures:

Title

Change in Liver Stiffness

Description

24 week minus baseline value, change in liver stiffness (kPa) measured by transient elastography (Fibroscan ®).

Time Frame

Baseline and 24 weeks

Title

Change in Fasting Plasma Glucose

Description

24 week value minus baseline value, change in fasting plasma glucose (mg/dL).

Time Frame

Baseline and 24 weeks

Title

Change in Fasting Serum Lipid Profile

Description

24 week value minus baseline value, change in fasting serum lipid profile: LDL and HDL cholesterol, triglyceride (all values in mmol/L)

Time Frame

Baseline and 24 weeks

Title

Change in Metabolic and Inflammatory Biomarkers: hsCRP

Description

24 week value minus baseline value, change in circulating metabolic and inflammatory biomarkers: high sensitivity C-reactive protein (hsCRP mg/L)

Time Frame

Baseline and 24 weeks

Title

Change in Metabolic and Inflammatory Biomarkers: IL-6

Description

24 week value minus baseline value, change in circulating metabolic and inflammatory biomarkers: interleukin 6 (IL-6 pg/mL)

Time Frame

Baseline and 24 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jussi Sutinen, MD PhD

Organizational Affiliation

Helsinki University Central Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Aurora hospital, Department of Infectious Diseases

City

Helsinki

Country

Finland

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

34524919

Citation

Hanttu A, Vuoti S, Kivela P, Arkkila P, Lundbom N, Hakkarainen A, Lundbom J, Lehtimaki T, Viskari H, Lehtinen V, Pietilainen KH, Sutinen J. Liver Fat, Adipose Tissue, and Body Composition Changes After Switching from a Protease Inhibitor or Efavirenz to Raltegravir. AIDS Patient Care STDS. 2021 Sep;35(9):335-341. doi: 10.1089/apc.2021.0106.

Results Reference

derived

Learn more about this trial

Effect on Liver Fat and Metabolic Parameters When Switching a Protease Inhibitor or Efavirenz to Raltegravir

We'll reach out to this number within 24 hrs