HIV InfectionPhase 4NCT00247494
Effects of Mycophenolate Mofetil (MMF) on Surrogate Markers for Cardiovascular Disease in HIV-1 Infected Patients
A Phase 4 study testing mycophenol mofetil (MMF, Cellcept®) 500 mg BID in people with HIV Infection and Atherosclerosis, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
Trial summary
This study is a substudy of the MAN2 -study (Mycophenol mofetil in Antiretroviral Naïve patients 2, see elsewhere in the ClinicalTrials.gov database). In the MAN2 study, HIV-1 infected patients who are not treated with antiretroviral treatment will be randomized to treatment with Mycophenol mofetil (MMF)500 mg BID or… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infection, Atherosclerosis
- What is being tested?
- mycophenol mofetil (MMF, Cellcept®) 500 mg BID
- How many people
- 90 participants
- Where
- 1 siteNetherlands
- Study dates
- Apr 2005to not given
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Any patient included in the MAN2-study van enter this substudy (see protocol MAN2 study)
Who cannot join
- Any condition, illness or use of medication which according to the investigator is not compatible with the conduct of the substudy or which could interfere with the evaluations required by the study.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site, 1 recruiting
- Recruiting
Department of Internal Medicine, Academic Medical Center, University of Amsterdam, The Netherlands
Amsterdam, North Holland, 1105 AZ
Sander I van Leuven, MD, +31 20 5668675, s.i.vanleuven@amc.uva.nl
Joost N Vermeulen, MD, +31 20 5668992, j.n.vermeulen@amc.uva.nl
About this study
This study is a substudy of the MAN2 -study (Mycophenol mofetil in Antiretroviral Naïve patients 2, see elsewhere in the ClinicalTrials.gov database). In the MAN2 study, HIV-1 infected patients who are not treated with antiretroviral treatment will be randomized to treatment with Mycophenol mofetil (MMF)500 mg BID or a control group without treatment (open label). Both patients randomized to treatment with MMF and patients randomized to the control group will be asked to participate also in this substudy.
In this substudy we want to show whether monotherapy with Mycophenol mofetil (MMF) in patients infected with HIV-1 can reduce acceleration of atherogenesis by attenuating various inflammatory pathways normally involved in progression of atherosclerosis.
Read the detailed description
- background Immune activation plays an important role in atherogenesis. In HIV-1 infection, the immune system is chronically hyperactivated. There also seems to be an increased incidence of cardiovascular disease in untreated HIV-1 infection. Mycophenol mofetil (MMF) will be used to treat this immune activation in untreated HIV-1 infected patients in the MAN2-study (see elsewhere in this ClinicalTrials.gov database).
- Hypothesis T-cell inhibition with MMF attenuates T-cell number, T-cell activation and T-cell - monocyte interaction, thereby minimizing the T-cell-driven inflammatory amplification loop.
In addition, MMF reduces expression of adhesion molecules on endothelial cells and leucocytes, thereby attenuating recruitment of circulating leucocytes to the atherosclerotic plaque. Combining these effects MMF treatment will improve anti-atherogenic defence mechanisms, such as improvement of endothelial function and attenuation of the pro-inflammatory state.
*design This will be a substudy of of the multi-center, double-blind, randomized, trial "Mycophenol mofetil in Antiretroviral Naïve patients 2 (MAN2 study)" (called the main study hereafter). The aim of the substudy is to evaluate the effects of mycophenolate mofetil on ´surrogate markers´ for atherosclerosis in a group of HIV-1 infected patients. All 90 patients to be included in the main study will be asked to participate in this substudy. A separate informed consent is needed.
Patients participating in this substudy will undergo study procedures for the substudy only on day 0 and week 48 of the main study (i.e. before the first dose of MMF and after 48 weeks of MMF treatment for the patients randomized to MMF treatment). Extra blood will be drawn to measure several biochemical markers associated with atherosclerosis and will be measured. Furthermore measurements of the condition of the blood vessels will be performed (using ultrasound, amongst others).
- Conditions
- HIV Infection, Atherosclerosis
- Being tested
- mycophenol mofetil (MMF, Cellcept®) 500 mg BID
- Keywords
- HIV-1, atherosclerosis, immunomodulation
- Medical subject headings
- HIV Infections, Atherosclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
mycophenol mofetil (MMF, Cellcept®) 500 mg BIDDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
The difference between the two groups (patients treated with MMF and the control group without treatment) in the change (week 0-week 48) in biochemical markers, Flow Mediated Dilation and Intima Media Thickness.
Secondary outcomes (1)
The change (week 0-week 48) within patients in biochemical markers, Flow Mediated Dilation and Intima Media Thickness.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Nov 2005 (estimated)
- Study startApr 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionStudies of the same condition, open and under way.
- More trials run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Investigators
- Erik S Stroes, MD PhD, Principal investigator, Department of Internal Medicine, Division of Vascular Medicine, Academic Medical Center, University of Amsterdam
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00247494
- Sponsor's protocol ID
- Myocardh
- Status last verified
- Nov 2005
- First submitted
- 1 Nov 2005
- Last updated
- 22 Jul 2009
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Allison AC, Eugui EM. Mycophenolate mofetil and its mechanisms of action. Immunopharmacology. 2000 May;47(2-3):85-118. doi: 10.1016/s0162-3109(00)00188-0.
PubMed 10878285Romero F, Rodriguez-Iturbe B, Pons H, Parra G, Quiroz Y, Rincon J, Gonzalez L. Mycophenolate mofetil treatment reduces cholesterol-induced atherosclerosis in the rabbit. Atherosclerosis. 2000 Sep;152(1):127-33. doi: 10.1016/s0021-9150(99)00458-x.
PubMed 10996347Greenstein SM, Sun S, Calderon TM, Kim DY, Schreiber TC, Schechner RS, Tellis VA, Berman JW. Mycophenolate mofetil treatment reduces atherosclerosis in the cholesterol-fed rabbit. J Surg Res. 2000 Jun 15;91(2):123-9. doi: 10.1006/jsre.2000.5919.
PubMed 10839960
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Mycophenolate Mofetil (MMF) on Surrogate Markers for Cardiovascular Disease in HIV-1 Infected Patients
- ClinicalTrials.gov ID
- NCT00247494
- Acronym / sponsor ID
- Myocardh
- Conditions
- HIV Infection, Atherosclerosis
- Keywords
- HIV-1, atherosclerosis, immunomodulation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)University, hospital or other
- Study start
- Apr 2005
- First posted
- 2 Nov 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is a substudy of the MAN2 -study (Mycophenol mofetil in Antiretroviral Naïve patients 2, see elsewhere in the ClinicalTrials.gov database). In the MAN2 study, HIV-1 infected patients who are not treated with antiretroviral treatment will be randomized to treatment with Mycophenol mofetil (MMF)500 mg BID or a control group without treatment (open label). Both patients randomized to treatment with MMF and patients randomized to the control group will be asked to participate also in this substudy.
In this substudy we want to show whether monotherapy with Mycophenol mofetil (MMF) in patients infected with HIV-1 can reduce acceleration of atherogenesis by attenuating various inflammatory pathways normally involved in progression of atherosclerosis.
Detailed description
- background Immune activation plays an important role in atherogenesis. In HIV-1 infection, the immune system is chronically hyperactivated. There also seems to be an increased incidence of cardiovascular disease in untreated HIV-1 infection. Mycophenol mofetil (MMF) will be used to treat this immune activation in untreated HIV-1 infected patients in the MAN2-study (see elsewhere in this ClinicalTrials.gov database).
- Hypothesis T-cell inhibition with MMF attenuates T-cell number, T-cell activation and T-cell - monocyte interaction, thereby minimizing the T-cell-driven inflammatory amplification loop.
In addition, MMF reduces expression of adhesion molecules on endothelial cells and leucocytes, thereby attenuating recruitment of circulating leucocytes to the atherosclerotic plaque. Combining these effects MMF treatment will improve anti-atherogenic defence mechanisms, such as improvement of endothelial function and attenuation of the pro-inflammatory state.
*design This will be a substudy of of the multi-center, double-blind, randomized, trial "Mycophenol mofetil in Antiretroviral Naïve patients 2 (MAN2 study)" (called the main study hereafter). The aim of the substudy is to evaluate the effects of mycophenolate mofetil on ´surrogate markers´ for atherosclerosis in a group of HIV-1 infected patients. All 90 patients to be included in the main study will be asked to participate in this substudy. A separate informed consent is needed.
Patients participating in this substudy will undergo study procedures for the substudy only on day 0 and week 48 of the main study (i.e. before the first dose of MMF and after 48 weeks of MMF treatment for the patients randomized to MMF treatment). Extra blood will be drawn to measure several biochemical markers associated with atherosclerosis and will be measured. Furthermore measurements of the condition of the blood vessels will be performed (using ultrasound, amongst others).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Any patient included in the MAN2-study van enter this substudy (see protocol MAN2 study)
Key exclusion criteria (1 listed)
- Any condition, illness or use of medication which according to the investigator is not compatible with the conduct of the substudy or which could interfere with the evaluations required by the study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| mycophenol mofetil (MMF, Cellcept®) 500 mg BID | Drug | – |
Primary outcome
The difference between the two groups (patients treated with MMF and the control group without treatment) in the change (week 0-week 48) in biochemical markers, Flow Mediated Dilation and Intima Media Thickness.
1 secondary outcome
The change (week 0-week 48) within patients in biochemical markers, Flow Mediated Dilation and Intima Media Thickness.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2009.
- Background: PubMed 10878285Allison AC, Eugui EM. Mycophenolate mofetil and its mechanisms of action. Immunopharmacology. 2000 May;47(2-3):85-118. doi: 10.1016/s0162-3109(00)00188-0.
- Background: PubMed 10996347Romero F, Rodriguez-Iturbe B, Pons H, Parra G, Quiroz Y, Rincon J, Gonzalez L. Mycophenolate mofetil treatment reduces cholesterol-induced atherosclerosis in the rabbit. Atherosclerosis. 2000 Sep;152(1):127-33. doi: 10.1016/s0021-9150(99)00458-x.
- Background: PubMed 10839960Greenstein SM, Sun S, Calderon TM, Kim DY, Schreiber TC, Schechner RS, Tellis VA, Berman JW. Mycophenolate mofetil treatment reduces atherosclerosis in the cholesterol-fed rabbit. J Surg Res. 2000 Jun 15;91(2):123-9. doi: 10.1006/jsre.2000.5919.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Erik S Stroes, MD PhD principal investigator
Department of Internal Medicine, Division of Vascular Medicine, Academic Medical Center, University of Amsterdam
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing mycophenol mofetil (MMF, Cellcept®) 500 mg BID in people with HIV Infection and Atherosclerosis, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Jul 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Sander I. van Leuven, MD (+31 20 5668675, s.i.vanleuven@amc.uva.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The difference between the two groups (patients treated with MMF and the control group without treatment) in the change (week 0-week 48) in biochemical markers, Flow Mediated Dilation and Intima Media Thickness.. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00247494, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jul 2009.