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

NCT03129113 | Completed Phase 2 DMC

• 1 other identifier: MAVMET
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 6

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

Conditions

Hepatic Steatosis; HIV-1-infection

Outcome Measures

Primary Outcomes (1)

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

  MR PDFF

  48 weeks

Study Arms (4)

maraviroc (Arm A)

EXPERIMENTAL

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

Drug: Maraviroc

metformin (Arm B)

EXPERIMENTAL

metformin 500mg BID p/o.

Drug: Metformin

maraviroc + metformin (Arm C)

EXPERIMENTAL

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

Drug: Maraviroc; Drug: Metformin

no adjunctive therapy (Arm D)

NO INTERVENTION

no adjunctive therapy

Interventions

Maraviroc DRUG

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

maraviroc (Arm A); maraviroc + metformin (Arm C)

Metformin DRUG

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

maraviroc + metformin (Arm C); metformin (Arm B)

Eligibility Criteria

• Age: 35 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University College, London: lead
• Medical Research Council: collaborator
• ViiV Healthcare: collaborator
• Royal Free Hospital NHS Foundation Trust: collaborator

Study Sites (6)

Royal London Hospital

London, E1 1FR, United Kingdom

Location

Royal Free Hospital

London, NW3 2QG, United Kingdom

Location

St Thomas' Hospital

London, SE1 9RT, United Kingdom

Location

King's College Hospital

London, SE5 9RJ, United Kingdom

Location

St Mary's Hospital

London, W2 1NY, United Kingdom

Location

UCL Mortimer Market Centre

London, WC1E 6JB, United Kingdom

Location

MeSH Terms

Conditions

Fatty Liver

Interventions

Maraviroc; Metformin

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Biguanides; Guanidines; Amidines

Study Officials

• Sarah Pett

  UCL

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Trial Manager

Model Details: 2 by 2 factorial randomisation to one of the 4 arms.

Study Record Dates

• First Submitted: April 21, 2017
• First Posted: April 26, 2017
• Study Start: March 1, 2017
• Primary Completion: November 5, 2020
• Study Completion: November 6, 2020
• Last Updated: November 4, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

GB (6)