Mycophenolate Mofetil in Antiretroviral Naïve Patients 2 (MAN2 Study)

NCT ID: NCT00120419

Last Updated: 2009-07-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

90 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-04-30

Brief Summary

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The purpose of the study is to evaluate whether mycophenolate mofetil (MMF) can treat the chronic hyperactivation of the immune system and (partly) prevent the decrease of the CD4+ T-cell count in chronically HIV-1 infected patients who are not treated with antiretroviral therapy (ART). The researchers also want to know what the effect is of treatment with MMF on plasma HIV-1 RNA; progression of disease (occurrence of AIDS defining events or reaching the indication to start ART); and the safety of treatment with MMF in this patient group.

Detailed Description

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\*Background: During chronic HIV-1 infection the immune system is chronically hyperactivated. This hyperactivation is considered as the main cause of CD4+ T-cell loss. Furthermore, HIV replicates most efficiently in activated CD4+ T-cells. In this study we try to inhibit the activation of the immune system with mycophenolate mofetil (MMF). Previous studies in which HIV-1 infected patients have been treated with MMF in addition to antiretroviral treatment (ART) have not shown any additional effect, compared to ART alone. In this study MMF will be used without antiretroviral medication.

\*Objectives: Primary objective of the study is the evaluation of the effect of MMF on the chronic hyperactivation of the immune system and the decrease of the CD4+ T-cell count in chronically HIV-1 infected patients who are not treated with antiretroviral therapy (ART). Secondary objectives include the evaluation of the effect of MMF on plasma HIV-1 RNA; progression of disease/ reaching of indication to start ART; and the safety of treatment with MMF in this patient group.

\*Study Design: This is a multi center, randomized, open-label study, in which patients will be randomized to treatment with mycophenolate mofetil (MMF) 500 mg BID during 48 weeks versus no treatment. In a subgroup of 20 patients ("immunology group", the first 20 patients in the AMC hospital, Amsterdam, the Netherlands) a number of additional immunological measurements will be performed.

The study duration is 60 weeks (48 weeks of treatments with 1 additional visit 12 weeks after cessation of treatment).

\*Study Population: Potential participants are adult chronically HIV-1 infected patients, who have never been treated with ART and who according to the present criteria do not need to be treated. CD4+ T lymphocyte count has to be \> 250 and \<= 450 \* 106/L, plasma HIV-1 RNA (viral load) \< 10.000 copies/ mL.

\*Intervention: Patients will be randomized (1:1) to mycofenolate mofetil (MMF) 500 mg BID versus no treatment.

\*Endpoints: Primary endpoints are change over time (baseline - week 48) in CD4+ T cell count and peripheral blood lymphocyte (PBMC) activation markers.

Secondary endpoints are changes over time (baseline - week 48) in plasma HIV-1 RNA, time to reach indication to start ART (separated in three groups: 1. two consecutive measurements of CD4+ T cell count below 250 \* 106 cells/ L with at least 4 weeks interval; 2. the occurrence of a CDC class B or C event; 3. any other reason); safety data.

Conditions

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HIV Infection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Interventions

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mycophenol mofetil (MMF, Cellcept®) 500 mg BID

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Patient is ≥ 18 years of age;
* Patient has a proven HIV-1 infection (with antibodies against HIV-1 and a detectable plasma HIV-1 RNA measured for the first time at least 6 months prior to inclusion);
* Patient is HIV-1 treatment naïve;
* CD4+ T lymphocyte count \> 250 and \<= 450 \* 106/L;
* No signs or history of AIDS defining events;
* No use of other medications that might possibly influence the effects of MMF;
* Male; or female sex and willingness to practice effective contraception during the study.

Exclusion Criteria

* Plasma HIV-1 RNA \< 10.000 copies/ mL;
* Autoimmune disease;
* Active hepatitis B or C virus infection;
* Other chronic diseases;
* Recent infectious disease other than HIV-1;
* Treatment with immunomodulatory or anti-inflammatory medication in the past 6 months;
* For female patients: pregnancy and lactation;
* Any other condition, illness or use of medication which according to the investigator is not compatible with the use of the study medication or which could interfere with the evaluations required by the study.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role collaborator

Sanquin Research & Blood Bank Divisions

OTHER

Sponsor Role collaborator

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

OTHER

Sponsor Role lead

Principal Investigators

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Jan M Prins, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Department of Internal Medicine, Division of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, University of Amsterdam, the Netherlands

Kees Brinkman, MD PhD

Role: PRINCIPAL_INVESTIGATOR

department of internal medicine, OLVG hospital, Amsterdam, the Netherlands

Robin Soetekouw, MD

Role: PRINCIPAL_INVESTIGATOR

department of internal medicine, Kennemer Gasthuis, Haarlem, the Netherlands

Robert Kauffmann, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Department of Internal Medicine, HAGA hospital, location Leyenburg Hospital, The Hague, The Netherlands

Locations

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OLVG

Amsterdam, North Holland, Netherlands

Site Status NOT_YET_RECRUITING

Academic Medical Center

Amsterdam, North Holland, Netherlands

Site Status RECRUITING

Kennemer Gasthuis, location EG

Haarlem, North Holland, Netherlands

Site Status NOT_YET_RECRUITING

Erasmus Medical Center

Rotterdam, South Holland, Netherlands

Site Status RECRUITING

HAGA hospital, location Leyenburg Hospital

The Hague, South Holland, Netherlands

Site Status NOT_YET_RECRUITING

Countries

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Netherlands

Central Contacts

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Joost N Vermeulen, MD

Role: CONTACT

+31 20 5668992

Jan M Prins, MD PhD

Role: CONTACT

+31 20 5669111

Facility Contacts

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Lucie Schrijnders-Gudde

Role: primary

+31 20 5999111 ext. 4626

Joost N Vermeulen, MD

Role: primary

+31 20 5668992

Jan M Prins, MD PhD

Role: backup

+31 20 566 9111

Robin Soetekouw, MD

Role: primary

+31 23 5453545

Iman Padmos

Role: primary

+31 (0)10-4635737

Robert H Kauffmann, MD PhD

Role: primary

+31 70-3592007

Anneke van IJperen

Role: backup

+31 70-3592414

References

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Chapuis AG, Paolo Rizzardi G, D'Agostino C, Attinger A, Knabenhans C, Fleury S, Acha-Orbea H, Pantaleo G. Effects of mycophenolic acid on human immunodeficiency virus infection in vitro and in vivo. Nat Med. 2000 Jul;6(7):762-8. doi: 10.1038/77489.

Reference Type BACKGROUND
PMID: 10888924 (View on PubMed)

Sankatsing SU, Jurriaans S, van Swieten P, van Leth F, Cornelissen M, Miedema F, Lange JM, Schuitemaker H, Prins JM. Highly active antiretroviral therapy with or without mycophenolate mofetil in treatment-naive HIV-1 patients. AIDS. 2004 Sep 24;18(14):1925-31. doi: 10.1097/00002030-200409240-00008.

Reference Type BACKGROUND
PMID: 15353978 (View on PubMed)

Garcia F, Plana M, Arnedo M, Brunet M, Castro P, Gil C, Vidal E, Millan O, Lopez A, Martorell J, Fumero E, Miro JM, Alcami J, Pumarola T, Gallart T, Gatell JM. Effect of mycophenolate mofetil on immune response and plasma and lymphatic tissue viral load during and after interruption of highly active antiretroviral therapy for patients with chronic HIV infection: a randomized pilot study. J Acquir Immune Defic Syndr. 2004 Jul 1;36(3):823-30. doi: 10.1097/00126334-200407010-00009.

Reference Type BACKGROUND
PMID: 15213566 (View on PubMed)

Other Identifiers

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MAN2-study

Identifier Type: -

Identifier Source: org_study_id

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