Adding MAraViroc &/or METformin for Hepatic Steatosis in People Living With HIV

NCT ID: NCT03129113

Last Updated: 2021-11-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

90 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-03-01

Study Completion Date

2020-11-06

Brief Summary

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This is a multicentre, phase IV, randomised, open-label, trial exploring adjunctive maraviroc and/or metformin for liver steatosis over 48 weeks.

Sponsored by University College London Coordinated by MRC Clinical Trials Unit at UCL

Detailed Description

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There is a global epidemic of obesity and/or being overweight. Fatty liver disease associated with overweight/obesity, can cause liver inflammation, which can lead to scarring of the liver (cirrhosis), liver cancer and early death. It is predicted that fatty liver disease will become the number one cause of liver cirrhosis in the next 20 years. There are no effective treatments, except weight loss, which is rarely successful.

In HIV-infected individuals, antiretroviral therapy (ART) is very successful at maintaining health long-term. However, despite this, data suggest that HIV-infected individuals are at greater risk of developing fatty liver disease than the general population, even if they are not overweight. Past exposure to some of the older, now obsolete, ART drugs, may have added to this greater risk. What makes things more difficult is that fatty liver disease can be 'silent' with no symptoms or signs until quite advanced.

MAVMET is trying to find out if maraviroc (licensed anti-HIV drug) and metformin (licensed for diabetes), given separately or in combination will reduce the amount of liver fat.

MAVMET participants are HIV-infected adult (aged at least 35), with HIV (but not hepatitis B/C) for 5 years or more, on combination ART for at least 1 year, and likely - because of abnormal liver tests and/or a large waist to have increased liver fat or already have a confirmed diagnosis of fatty liver disease, on a previous scan or a liver biopsy.

Participants will continue on their current ART and be randomised (like the flip of a coin) to receive 48 weeks of maraviroc (Arm A) or metformin (Arm B) or both drugs (Arm C) or no additional drugs (Arm D). Participants have 7 clinic visits over 48 weeks to monitor progress and 2 magnetic liver scans (MRI) (no radiation) at University College Hospital to measure liver fat. Mortimer Market Centre participants can also have optional brain MRI at the Institute of Neurology.

Patients can enrol at one of 3 sites: Mortimer Market Centre, St.Thomas's Hospital, King's College Hospital, London.

Conditions

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Hepatic Steatosis HIV-1-infection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

2 by 2 factorial randomisation to one of the 4 arms.
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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maraviroc (Arm A)

maraviroc dosed BID p/o (dose adjusted depending on background combination antiretroviral therapy).

Group Type EXPERIMENTAL

Maraviroc

Intervention Type DRUG

1:1:1:1 randomisation to one of four arms for 48 weeks

metformin (Arm B)

metformin 500mg BID p/o.

Group Type EXPERIMENTAL

Metformin

Intervention Type DRUG

1:1:1:1 randomisation to one of four arms for 48 weeks

maraviroc + metformin (Arm C)

maraviroc dosed BID p/o (dose adjusted depending on background combination antiretroviral therapy) PLUS metformin 500mg BID p/o.

Group Type EXPERIMENTAL

Maraviroc

Intervention Type DRUG

1:1:1:1 randomisation to one of four arms for 48 weeks

Metformin

Intervention Type DRUG

1:1:1:1 randomisation to one of four arms for 48 weeks

no adjunctive therapy (Arm D)

no adjunctive therapy

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Maraviroc

1:1:1:1 randomisation to one of four arms for 48 weeks

Intervention Type DRUG

Metformin

1:1:1:1 randomisation to one of four arms for 48 weeks

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Signed informed consent
2. Males or females ≥35 years of age
3. Chronic HIV-1-infection for ≥5 years
4. On combination antiretroviral therapy (cART) and with virological suppression (\<50 copies/mL) for ≥1 year
5. i) \>1 abnormal (above the upper limit) of LFTS (ALT or AST) in the last 2 years with no other explanation (e.g. secondary syphilis) and/or ii) increased waist circumference ≥94 cm (≥90cm if South Asian origin) in men, ≥80cm in women and/or iii) a confirmed diagnosis of NAFLD on liver imaging (CT/MRI/ultrasound), FibroScan and/or iv) liver biopsy confirmed diagnosis of NALFD
6. Females of child bearing potential (CBP) who agree to avoid pregnancy for the duration of the trial
7. Able to comply with protocol requirements

Exclusion Criteria

1. Co-infection with hepatitis B or C
2. Confirmed chronic liver disease from any other cause (e.g. hepatitis C, hepatitis B)
3. Daily intake of alcohol \>20g in women and \>30g in men
4. Current illicit drug use that in the opinion of the investigator would interfere with patient's ability to comply with the protocol
5. On metformin or another biguanide agent;
6. Currently on maraviroc
7. Any contraindication to the receipt of maraviroc and/or metformin
8. Known B12 deficiency
9. Pregnant or breast feeding
10. Contraindication to MRI scanning
11. Peanut or soya allergy
12. eGFR \<60 ml/min/1.73m2
13. ALT ≥10 x ULN
14. History of cardiovascular (ischaemic heart disease) or cerebrovascular disease.
15. Any other condition that in the opinion of the investigator would not make the patient suitable for the trial.
Minimum Eligible Age

35 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Medical Research Council

OTHER_GOV

Sponsor Role collaborator

ViiV Healthcare

INDUSTRY

Sponsor Role collaborator

Royal Free Hospital NHS Foundation Trust

OTHER

Sponsor Role collaborator

University College, London

OTHER

Sponsor Role lead

Responsible Party

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ADAM CURSLEY

Trial Manager

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Sarah Pett

Role: PRINCIPAL_INVESTIGATOR

UCL

Locations

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Royal London Hospital

London, , United Kingdom

Site Status

Royal Free Hospital

London, , United Kingdom

Site Status

St Thomas' Hospital

London, , United Kingdom

Site Status

King's College Hospital

London, , United Kingdom

Site Status

St Mary's Hospital

London, , United Kingdom

Site Status

UCL Mortimer Market Centre

London, , United Kingdom

Site Status

Countries

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United Kingdom

Other Identifiers

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MAVMET

Identifier Type: -

Identifier Source: org_study_id