- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03129113
Adding MAraViroc &/or METformin for Hepatic Steatosis in People Living With HIV (MAVMET)
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.
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
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 3
Contacts and Locations
Study Locations
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-
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London, United Kingdom, E1 1FR
- Royal London Hospital
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London, United Kingdom, NW3 2QG
- Royal Free Hospital
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London, United Kingdom, W2 1NY
- St Mary's Hospital
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London, United Kingdom, SE5 9RJ
- King's College Hospital
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London, United Kingdom, SE1 9RT
- St Thomas' Hospital
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London, United Kingdom, WC1E 6JB
- UCL Mortimer Market Centre
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
- 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
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Factorial Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: maraviroc (Arm A)
maraviroc dosed BID p/o (dose adjusted depending on background combination antiretroviral therapy).
|
1:1:1:1 randomisation to one of four arms for 48 weeks
|
Experimental: metformin (Arm B)
metformin 500mg BID p/o.
|
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.
|
1:1:1:1 randomisation to one of four arms for 48 weeks
1:1:1:1 randomisation to one of four arms for 48 weeks
|
No Intervention: no adjunctive therapy (Arm D)
no adjunctive therapy
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in percentage of liver fat as measured by MR PDFF between baseline and week 48.
Time Frame: 48 weeks
|
MR PDFF
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48 weeks
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Sarah Pett, UCL
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Liver Diseases
- Fatty Liver
- Hypoglycemic Agents
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Anti-HIV Agents
- Anti-Retroviral Agents
- HIV Fusion Inhibitors
- Viral Fusion Protein Inhibitors
- CCR5 Receptor Antagonists
- Metformin
- Maraviroc
Other Study ID Numbers
- MAVMET
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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