NCT03374358: OBERAL

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

Completed Phase 4 Results posted Last updated 5 September 2021

What this trial tests

Phase 4 trial testing Raltegravir in HIV Seropositivity in 45 participants. Completed in 30 November 2019.

Timeline

10 January 2018

Primary endpoint
2 November 2019

30 November 2019

Quick facts

Lead sponsor	Helsinki University Central Hospital
Phase	Phase 4
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	45
Start date	10 January 2018
Primary completion	2 November 2019
Estimated completion	30 November 2019
Sites	1 location across Finland

Drugs / interventions tested

• Raltegravir — full drug profile →

Conditions studied

• HIV Seropositivity — all drugs for HIV Seropositivity →
• Metabolic Syndrome — all drugs for Metabolic Syndrome →
• Fatty Liver — all drugs for Fatty Liver →

Sponsor

Helsinki University Central Hospital

Who can join

18 and older, any sex, with HIV Seropositivity or Metabolic Syndrome. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change in Liver Fat Primary · Baseline and 24 weeks

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

Group	Value	95% CI
Control (= no Intervention Arm).	0.3	-0.5 – 2.7
Raltegravir Arm.	0.6	-0.3 – 1.6

Change in Subcutaneous and Visceral Adipose Tissue Volume Secondary · Baseline and 24 weeks

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 SAT (24 weeks - baseline)

Group	Value	95% CI
Control (= no Intervention Arm).	-74	-627 – 202
Raltegravir Arm.	242	27 – 341

Change in VAT (24 weeks - baseline)

Group	Value	95% CI
Control (= no Intervention Arm).	100	-126 – 569
Raltegravir Arm.	66	-149 – 299

Change in Body Weight and Total Body Fat Secondary · Baseline and 24 weeks

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

Change in body weight (24 weeks - baseline)

Group	Value	95% CI
Control (= no Intervention Arm).	0.9	-1.8 – 4.1
Raltegravir Arm.	2.0	0.4 – 3.3

Change in body fat (24 weeks - baseline)

Group	Value	95% CI
Control (= no Intervention Arm).	-0.3	-1.7 – 1.5
Raltegravir Arm.	1.5	0.1 – 2.5

Change in Liver Stiffness Secondary · Baseline and 24 weeks

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

Group	Value	95% CI
Control (= no Intervention Arm).	-0.5	-1.2 – 0.6
Raltegravir Arm.	-0.2	-1.6 – 0.9

Change in Fasting Plasma Glucose Secondary · Baseline and 24 weeks

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

Group	Value	95% CI
Control (= no Intervention Arm).	0.0	-7.2 – 5.4
Raltegravir Arm.	-1.8	-10.8 – 0.0

Change in Fasting Serum Lipid Profile Secondary · Baseline and 24 weeks

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

Change in fasting serum LDL (24 weeks - baseline)

Group	Value	95% CI
Control (= no Intervention Arm).	0.1	-0.4 – 0.4
Raltegravir Arm.	-0.5	-1.0 – -0.1

Change in fasting serum HDL (24 weeks - baseline)

Group	Value	95% CI
Control (= no Intervention Arm).	0.04	-0.07 – 0.15
Raltegravir Arm.	-0.07	-0.16 – -0.01

Change in fasting serum triglycerides (24 weeks - baseline)

Group	Value	95% CI
Control (= no Intervention Arm).	-0.05	-0.28 – 0.20
Raltegravir Arm.	-0.18	-0.49 – 0.19

Change in Metabolic and Inflammatory Biomarkers: hsCRP Secondary · Baseline and 24 weeks

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

Group	Value	95% CI
Control (= no Intervention Arm).	0.66	-0.07 – 1.45
Raltegravir Arm.	-0.06	-0.59 – 0.22

Change in Metabolic and Inflammatory Biomarkers: IL-6 Secondary · Baseline and 24 weeks

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

Group	Value	95% CI
Control (= no Intervention Arm).	0.83	-0.09 – 1.20
Raltegravir Arm.	0.00	-0.87 – 0.64

Adverse events — posted to ClinicalTrials.gov

Time frame: 6 months.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Control (= no Intervention Arm).

Serious: 1/24 (4%)

Deaths: 0/24

Raltegravir Arm.

Serious: 0/19 (0%)

Deaths: 0/19

Serious adverse events (1 terms)

Reaction	System	Control (= no Intervention…	Raltegravir Arm.
Acute pancreatitis	Gastrointestinal disorders	—	—

Other adverse events (6 terms — click to expand)

Reaction	System	Control (= no Intervention…	Raltegravir Arm.
Sleeping difficulties	Psychiatric disorders	—	—
Headache	Nervous system disorders	—	—
Gastrointestinal (diarrhoea, nausea)	Gastrointestinal disorders	—	—
Nervousness	Psychiatric disorders	—	—
Dizzyness	Nervous system disorders	—	—
Depressed mood	Psychiatric disorders	—	—

Most-reported serious reactions: Acute pancreatitis.

Data from ClinicalTrials.gov NCT03374358 adverse events section.

Sponsor's own description

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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Liver Fat, Adipose Tissue, and Body Composition Changes After Switching from a Protease Inhibitor or Efavirenz to Raltegravir.
   Hanttu A, Vuoti S, Kivelä P, Arkkila P, et al · · 2021 · cited 7× · PMID 34524919 · DOI 10.1089/apc.2021.0106