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

NCT03374358 | Completed Phase 4 Results

• 1 other identifier: OBERAL
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

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.

Conditions

HIV Seropositivity; Metabolic Syndrome; Fatty Liver

Outcome Measures

Primary Outcomes (1)

• Change in Liver Fat

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

  Baseline and 24 weeks

Secondary Outcomes (2)

• Change in Subcutaneous and Visceral Adipose Tissue Volume

  Baseline and 24 weeks

• Change in Body Weight and Total Body Fat

  Baseline and 24 weeks

Other Outcomes (5)

• Change in Liver Stiffness

  Baseline and 24 weeks

• Change in Fasting Plasma Glucose

  Baseline and 24 weeks

• Change in Fasting Serum Lipid Profile

  Baseline and 24 weeks

Study Arms (2)

No intervention arm.

NO INTERVENTION

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

Raltegravir arm.

EXPERIMENTAL

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

Drug: Raltegravir

Interventions

Raltegravir DRUG

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 .

Also known as: Isentress

Raltegravir arm.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Helsinki University Central Hospital: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Aurora hospital, Department of Infectious Diseases

Helsinki, Finland

Location

Related Publications (2)

• Hanttu AM, Pekkala S, Satokari R, Hartikainen AK, Arkkila P, Pietilainen KH, Sutinen JP. Gut microbiota alterations after switching from a protease inhibitor or efavirenz to raltegravir in a randomized, controlled study. AIDS. 2023 Feb 1;37(2):323-332. doi: 10.1097/QAD.0000000000003419. Epub 2022 Nov 10.

  PMID: 36541643 DERIVED

• 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.

  PMID: 34524919 DERIVED

MeSH Terms

Conditions

HIV Seropositivity; Metabolic Syndrome; Fatty Liver

Interventions

Raltegravir Potassium

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr Jussi Sutinen
• Organization: Helsinki University Hospital

jussi.sutinen@hus.fi

+358407480437

Study Officials

• Jussi Sutinen, MD PhD

  Helsinki University Central Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant, MD, PhD

Model Details: This study is a randomized, open, parallel design study.

Study Record Dates

• First Submitted: December 2, 2017
• First Posted: December 15, 2017
• Study Start: January 10, 2018
• Primary Completion: November 2, 2019
• Study Completion: November 30, 2019
• Last Updated: September 5, 2021
• Results First Posted: July 7, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

FI (1)