Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03129113
Recruitment Status : Completed
First Posted : April 26, 2017
Last Update Posted : November 4, 2021
Sponsor:
Collaborators:
Medical Research Council
ViiV Healthcare
Royal Free Hospital NHS Foundation Trust
Information provided by (Responsible Party):
ADAM CURSLEY, University College, London

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Intervention Model Description: 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 : March 1, 2017
Actual Primary Completion Date : November 5, 2020
Actual Study Completion Date : November 6, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

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



Primary Outcome Measures :
  1. Change in percentage of liver fat as measured by MR PDFF between baseline and week 48. [ Time Frame: 48 weeks ]
    MR PDFF



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   35 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

PATIENT 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

PATIENT 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03129113


Locations
Layout table for location information
United Kingdom
Royal London Hospital
London, United Kingdom, E1 1FR
Royal Free Hospital
London, United Kingdom, NW3 2QG
St Thomas' Hospital
London, United Kingdom, SE1 9RT
King's College Hospital
London, United Kingdom, SE5 9RJ
St Mary's Hospital
London, United Kingdom, W2 1NY
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
Layout table for investigator information
Principal Investigator: Sarah Pett UCL
Layout table for additonal information
Responsible Party: ADAM CURSLEY, Trial Manager, University College, London
ClinicalTrials.gov Identifier: NCT03129113    
Other Study ID Numbers: MAVMET
First Posted: April 26, 2017    Key Record Dates
Last Update Posted: November 4, 2021
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Fatty Liver
Liver Diseases
Digestive System Diseases
Metformin
Maraviroc
Hypoglycemic Agents
Physiological Effects of Drugs
HIV Fusion Inhibitors
Viral Fusion Protein Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
CCR5 Receptor Antagonists