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

Sponsor

University College, London (Other)

Overall Status

Completed

CT.gov ID

NCT03129113

Collaborator

Medical Research Council (Other), ViiV Healthcare (Industry), Royal Free Hospital NHS Foundation Trust (Other)

Enrollment

Locations

Arms

44.2

Actual Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Hepatic Steatosis HIV-1-infection	Drug: Maraviroc Drug: Metformin	Phase 2/Phase 3

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

90 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Intervention Model Description:

2 by 2 factorial randomisation to one of the 4 arms.2 by 2 factorial randomisation to one of the 4 arms.

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Multicentre, 48 Week Randomised Controlled Factorial Trial of Adding Maraviroc and/or Metformin for Hepatic Steatosis in HIV-1-infected Adults on Combination Antiretroviral Therapy.

Actual Study Start Date :

Mar 1, 2017

Actual Primary Completion Date :

Nov 5, 2020

Actual Study Completion Date :

Nov 6, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: maraviroc (Arm A) maraviroc dosed BID p/o (dose adjusted depending on background combination antiretroviral therapy).	Drug: Maraviroc 1:1:1:1 randomisation to one of four arms for 48 weeks
Experimental: metformin (Arm B) metformin 500mg BID p/o.	Drug: Metformin 1:1:1:1 randomisation to one of four arms for 48 weeks
Experimental: maraviroc + metformin (Arm C) maraviroc dosed BID p/o (dose adjusted depending on background combination antiretroviral therapy) PLUS metformin 500mg BID p/o.	Drug: Maraviroc 1:1:1:1 randomisation to one of four arms for 48 weeks Drug: Metformin 1:1:1:1 randomisation to one of four arms for 48 weeks
No Intervention: no adjunctive therapy (Arm D) no adjunctive therapy

Outcome Measures

Primary Outcome Measures

Change in percentage of liver fat as measured by MR PDFF between baseline and week 48. [48 weeks]
MR PDFF

Eligibility Criteria

Criteria

Ages Eligible for Study:

35 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

PATIENT INCLUSION CRITERIA

Signed informed consent
Males or females ≥35 years of age
Chronic HIV-1-infection for ≥5 years
On combination antiretroviral therapy (cART) and with virological suppression (<50 copies/mL) for ≥1 year
1. 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

liver biopsy confirmed diagnosis of NALFD

Females of child bearing potential (CBP) who agree to avoid pregnancy for the duration of the trial
Able to comply with protocol requirements

PATIENT EXCLUSION CRITERIA

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Royal London Hospital	London	United Kingdom	E1 1FR
2	Royal Free Hospital	London	United Kingdom	NW3 2QG
3	St Thomas' Hospital	London	United Kingdom	SE1 9RT
4	King's College Hospital	London	United Kingdom	SE5 9RJ
5	St Mary's Hospital	London	United Kingdom	W2 1NY
6	UCL Mortimer Market Centre	London	United Kingdom	WC1E 6JB

Sponsors and Collaborators

University College, London
Medical Research Council
ViiV Healthcare
Royal Free Hospital NHS Foundation Trust

Investigators

Principal Investigator: Sarah Pett, UCL

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

ADAM CURSLEY, Trial Manager, University College, London

ClinicalTrials.gov Identifier:

NCT03129113

Other Study ID Numbers:

MAVMET

First Posted:

Apr 26, 2017

Last Update Posted:

Nov 4, 2021

Last Verified:

Nov 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Fatty Liver

Metformin

Maraviroc

Study Results

No Results Posted as of Nov 4, 2021