Mycophenolate Mofetil in Antiretroviral Naïve Patients 2 (MAN2 Study) - Full Text View

Sponsor:	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Collaborators:	Hoffmann-La Roche Sanquin Research & Blood Bank Divisions
Information provided by:	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier:	NCT00120419

Purpose

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.

Condition	Intervention	Phase
HIV Infection	Drug: mycophenol mofetil (MMF, Cellcept®) 500 mg BID	Phase IV

Study Type:	Interventional
Study Design:	Prevention, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Resource links provided by NLM:

MedlinePlus related topics: AIDS

Drug Information available for: Mycophenolate mofetil hydrochloride Mycophenolate Mofetil

U.S. FDA Resources

Further study details as provided by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):

Primary Outcome Measures:

Change over time (baseline - week 48) in CD4+ cell counts in peripheral blood and peripheral blood lymphocyte activation markers.

Secondary Outcome Measures:

* Change over time (baseline - week 48) in plasma HIV-1 RNA, time to reach an indication to start antiretroviral treatment and safety parameters.

Estimated Enrollment:	90
Study Start Date:	April 2005

Detailed Description:

*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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00120419

Contacts

Contact: Joost N Vermeulen, MD	+31 20 5668992	j.n.vermeulen@amc.uva.nl
Contact: Jan M Prins, MD PhD	+31 20 5669111	j.m.prins@amc.uva.nl

Locations

Netherlands, NH
Academic Medical Center	Recruiting
Amsterdam, NH, Netherlands, 1105 AZ
Contact: Joost N Vermeulen, MD +31 20 5668992 j.n.vermeulen@amc.uva.nl
Contact: Jan M Prins, MD PhD +31 20 566 9111 j.m.prins@amc.uva.nl
Principal Investigator: Jan M Prins, MD PhD
Sub-Investigator: Joost N Vermeulen, MD
Kennemer Gasthuis, location EG	Not yet recruiting
Haarlem, NH, Netherlands, 2035RC
Contact: Robin Soetekouw, MD +31 23 5453545 soetekou@KG.NL
Principal Investigator: Robin Soetekouw, MD
OLVG	Not yet recruiting
Amsterdam, NH, Netherlands, 1091AC
Contact: Lucie Schrijnders-Gudde +31 20 5999111 ext 4626 L.Schrijnders-Gudde@olvg.nl
Principal Investigator: Kees Brinkman, MD PhD
Sub-Investigator: H. M. Weigel, MD
Sub-Investigator: P. H. Frissen, MD PhD
Sub-Investigator: W. E. Schouten, MD PhD
Netherlands, ZH
HAGA hospital, location Leyenburg Hospital	Not yet recruiting
The Hague, ZH, Netherlands, 2545 CH
Contact: Robert H Kauffmann, MD PhD +31 70-3592007 r.kauffmann@leyenburg-ziekenhuis.nl
Contact: Anneke van IJperen +31 70-3592414 j.maat@leyenburg-ziekenhuis.nl
Principal Investigator: Robert H Kauffman, MD PhD
Erasmus Medical Center	Recruiting
Rotterdam, ZH, Netherlands, 3015GD
Contact: Iman Padmos +31 (0)10-4635737 i.padmos@erasmusmc.nl
Principal Investigator: Ineke van der Ende, MD PhD

Sponsors and Collaborators

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

Hoffmann-La Roche

Sanquin Research & Blood Bank Divisions

Investigators

Principal Investigator:	Jan M Prins, MD PhD	Department of Internal Medicine, Division of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, University of Amsterdam, the Netherlands
Principal Investigator:	Kees Brinkman, MD PhD	department of internal medicine, OLVG hospital, Amsterdam, the Netherlands
Principal Investigator:	Robin Soetekouw, MD	department of internal medicine, Kennemer Gasthuis, Haarlem, the Netherlands
Principal Investigator:	Robert Kauffmann, MD PhD	Department of Internal Medicine, HAGA hospital, location Leyenburg Hospital, The Hague, The Netherlands

More Information

Publications:

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.

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.

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):823-830.

Study ID Numbers:	MAN2-study
Study First Received:	July 11, 2005
Last Updated:	July 21, 2009
ClinicalTrials.gov Identifier:	NCT00120419 History of Changes
Health Authority:	Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):

HIV-1 infection
immunomodulatory therapy
Treatment Naive

Additional relevant MeSH terms:

Communicable Diseases
RNA Virus Infections
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Immunologic Factors
Immune System Diseases
Physiological Effects of Drugs
Acquired Immunodeficiency Syndrome
Infection

Immunosuppressive Agents
Pharmacologic Actions
Immunologic Deficiency Syndromes
Virus Diseases
HIV Infections
Sexually Transmitted Diseases
Mycophenolate mofetil
Lentivirus Infections
Retroviridae Infections

ClinicalTrials.gov processed this record on February 08, 2010