Investigating the effect of maraviroc on Microbial Translocation in HIV infected individuals who are receiving antiretroviral therapy
| ISRCTN | ISRCTN81045654 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN81045654 |
| Secondary identifying numbers | JF003 |
- Submission date
- 19/04/2011
- Registration date
- 19/07/2011
- Last edited
- 09/11/2017
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year
Plain English summary of protocol
Not provided at time of registration
Contact information
Dr Alastair Teague
Scientific
Scientific
Harrison Wing
2nd Floor Lambeth Wing
St. Thomas' Hospital
Westminster Bridge Rd
London
SE1 7EH
United Kingdom
Study information
| Study design | Phase IV prospective intervention study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | Investigating the effect of maraviroc on Microbial Translocation in HIV infected individuals who are receiving antiretroviral therapy: a phase IV, prospective, intervention study |
| Study acronym | MT Study |
| Study objectives | This is a proof of concept study investigating a novel mechanism for the impact of maraviroc on clinical outcome |
| Ethics approval(s) | St. Thomas' REC approval pending as of 20/04/2011 |
| Health condition(s) or problem(s) studied | Human immunodeficiency virus (HIV) |
| Intervention | In this non-randomised study, maraviroc will be given according to the Summary of Product Characteristics (SmPC) for 24 weeks. Maraviroc (dose based on current medications in regimen as per SmPC): 1.150 mg orally two times a day (PO BID) for those on a protease inhibitor-based regimen other than Tipranavir 2. 600 mg PO BID for efavirenz-containing regimens 3. 300 mg PO BID for all other regimens Total duration of study is 24 weeks, plus screening period. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase IV |
| Drug / device / biological / vaccine name(s) | Maraviroc |
| Primary outcome measure | Microbial translocation: soluble CD14a level Measured at baseline, wk 2, wk 4, wk 12 and wk 24 |
| Secondary outcome measures | 1. Level of gut permeability/microbial translocation: bacterial 16s DNA will be quantified by polymerase chain reaction (PCR) 2. Th17 Tc17/MAIT cell quantification: Flow cytometry will quantify CD161+ T cells (CD4+ and CD8+) expressing IL17, Il22 and IFNg 3. Natural killer cell (NK) function: As markers of NK function, CD3-, CD161+ NK cell subset frequencies will be quantified and their secretion of IFNg, (also IL17 and IL22) analysed 4. Immune activation: As markers of CD8 T-cell activation, the percentage of CD3+ CD8+ cells expressing CD38+ and HLA-DR and PD-1 will be analysed 5. Clinical outcome: CD4+ T cell count change, HIV plasma viral load 6. Biomarkers of inflammation: Inflammatory cytokines will be analysed using a cytometric bead array (CBA) assay (IL-6, TNF and D-dimer) will be evaluated and their relationship to gut permeability and immune activation investigated 7. Low copy viral quantification of cell associated plasma and tissue cell-associated HIV DNA and HIV RNA by real-time polymerase chain reaction (PCR) and/or in situ hybridisation 8. Neurocognitive function: formal neurocognitive tests will be carried out to investigate the relationship between microbial translocation and neurocognitive function 9. Immune reconstitution/HIV specific immune function will be evaluated using intracellular cytokine staining (TNFa, IFNg, IL2, IL17) following in vitro HIV-derived antigenic stimulation by co-culture of peripheral blood mononuclear cell (PBMC) with gag peptides 10. Immunohistochemistry (gut only) will investigate the distribution of GALT (CD3, CD4, CD8), immune activation (CD38, Ki67), innate cells (T reg cells (FoxP3), dendritic cells (CD23), macrophages (CD68), gut permeability (ZO-1, occludin, claudins 1, 2, 5 and 8) and epithelial apoptosis (TUNEL) 11. Gut derived lymphocytes: Paired blood and gut derived lymphocyte samples will be analysed for the frequencies of CD3+ CD4+ or CD3+ CD8+ T cells expressing CD161 and secreting IL17 Measured at baseline, wk 2, wk 4, wk 12 and wk 24 |
| Overall study start date | 01/09/2011 |
| Completion date | 01/09/2012 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 70 Years |
| Sex | Both |
| Target number of participants | 10 |
| Key inclusion criteria | 1. Males and females aged between 18-70 with confirmed human immunodeficiency virus (HIV)-1 infection 2. Patients on stable antiretroviral therapy for at least 12 months 3. Screening CD4+ T cell count below 350 cells/mm3 4. All available CD4+ T cell counts in the last year and at screening < 350 cells/mm3 5. Screening plasma HIV ribonucleic acid (RNA) levels below 100copies RNA/mL 6. All available plasma HIV RNA levels within past 6-months below the level of detection. Isolated values that are detectable but < 500 copies will be allowed as long as the plasma HIV RNA levels before and after this time point are undetectable. 7. Females of childbearing potential must have a negative serum pregnancy test at screening and agree to use a double-barrier method of contraception throughout the study period and at least 28 days after last dose of study drug. Effective methods include condoms in combination with a female condom, diaphragm, intrauterine device, hormonal contraceptives (oral, implants, injectable), abstinence, vasectomy or tubal ligation. 8. Ability and willingness of subject to provide informed consent |
| Key exclusion criteria | 1. Patient unlikely to comply with protocol, and in particular adhere to therapeutic regimen 2. Patient likely to use narcotics during the study period 3. Increase in CD4 count of > 100 cells/mm3 in past year 4. Patients who are intending to modify antiretroviral therapy in the next 24 weeks for any reason 5. Serious illness requiring hospitalization or parental antibiotics within preceding 3 months 6. Concurrent treatment with immunomodulatory drugs, or exposure to any immunomodulatory drug in past 16 weeks 7. Hepatitis B surface antigen (HBVsAg+) or active hepatitis C or hepatitis B which will require treatment in the subsequent 24 weeks 8. Prior exposure to chemokine (C-C motif) receptor 5 (CCR5) inhibitors 9. Estimated creatinine clearance < 40 mL/minute 10. Pregnant or breastfeeding women 11. Use of both tenofovir and didanosine in current antiretroviral therapy regimen |
| Date of first enrolment | 01/09/2011 |
| Date of final enrolment | 01/09/2012 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
St. Thomas' Hospital
London
SE1 7EH
United Kingdom
SE1 7EH
United Kingdom
Sponsor information
Guys & St Thomas' NHS Foundation Trust (UK)
Hospital/treatment centre
Hospital/treatment centre
Joint Clinical trials Office
16th Floor Tower Wing
Guys Hospital
Great Maze Pond
London
SE1 9RT
England
United Kingdom
"ROR" |
https://ror.org/00j161312 |
|---|
Funders
Funder type
Industry
Viiv Healthcare (UK)
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Editorial Notes
09/11/2017: No publications found in PubMed, verifying study status with principal investigator.
