Cytomegalovirus InfectionNCT00817908
Quantiferon - Cytomegalovirus (CMV) and the Prediction of CMV Infection In High Risk Solid Organ Transplant Recipients
An observational study of Cytomegalovirus Infection, run by University of Alberta at 1 site in Canada.
Trial summary
Cytomegalovirus (CMV) is a common cause of illness in patients who have undergone a transplant. Serious infections due to CMV can affect many parts of the body including the lungs, the gut, and the liver. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cytomegalovirus Infection
- How many people
- 131 participants
- Where
- 1 siteCanada
- Study dates
- May 2008to Apr 2012
- Phase
- Observational
- 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
Study population: The study will aim to enrol 120 D+/R- transplant patients.
Who may be able to join
- Male or female patients who fulfill the following criteria are eligible for inclusion.
- CMV D+/R- liver, kidney, heart, pancreas, lungor combined transplant recipients
- All eligible patients must be scheduled to receive 3 months of either valganciclovir, oral ganciclovir, or intravenous ganciclovir prophylaxis.
- Able to give written informed consent
- Are willing and able to comply with the protocol
- Age >=18 years
Who cannot join
- Patient unwilling or unable to give informed consent
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Quantiferon - CMV and the Prediction of CMV Infection In High Risk Solid Organ Transplant Recipients
Cytomegalovirus (CMV) is a common cause of illness in patients who have undergone a transplant. Serious infections due to CMV can affect many parts of the body including the lungs, the gut, and the liver. Since transplant recipients are at risk for CMV or have evidence of infection with CMV, they are given an antiviral drug (usually ganciclovir or valganciclovir). Despite this, there are a chance that CMV infection may cause problems in the future. The purpose of this study is to assess how well patients'immune systems responds to the CMV virus, so that in the future it may be possible to predict which patients are at highest risk of CMV.
Read the detailed description
CMV is the most common viral infection after solid organ transplantation (SOT) and is associated with significant morbidity1. Without prophylaxis, most CMV disease occurs in the first 3 months post-transplant during the period of intense of immunosuppresion.2 SOT recipients at the greatest risk are those that are seronegative recipients of organs from seropositive donors (CMV D+/R-).3, 4 Antiviral agents have proven to be useful in the prevention of CMV infection and disease in SOT recipients, including the high-risk D+/R- patients.5-9 Upon completion of prophylaxis however, CMV infection and disease occurs in about 50% and 25-30% respectively of D+/R- SOT recipients within the first year after transplant [30% rate of investigator treated CMV disease in PV16000].9 The incidence of CMV infection following prophylaxis in D+/R- lung transplant recipients may be as high as 80%.10 As CMV disease occurring after prophylaxis will continue to impact morbidity and mortality in SOT recipients, it would be desirable to be able to predict which patient will develop this complication. Currently, there are no reliable methods that are routinely available to predict the risk of CMV infection or disease in an individual patient. CMV viral load testing after prophylaxis in D+/R- patients has been shown to have poor predictive value for subsequent CMV disease.11 CMV serology (a measure of humoral immunity) was also shown to be only of marginal use in predicting the risk of late onset disease.12 Cell mediated immunity (CMI) is known to be more important than humoral immunity in controlling CMV infection. CMV infection elicits a strong virus specific CD4+ and CD8+ T-cell response. CD8+ T-cell responses to the virus often contain multiple antigen-specific reactivities including to viral pp65 or IE-1 antigens as well as pp50, glycoprotein B, and IE-2 and other antigens.13 CD4+ T cells also play a part in CMV control via promotion of priming, expansion and maintenance of CD8+ CMV-specific CTLs.14 Measuring an individual's CMI response to CMV may be a useful predictor of the risk of CMV infection or disease after prophylaxis. Patients with a poor CMI response (especially a poor CD8+ T-cell response) could then be targeted with longer courses of antiviral prophylaxis.
Cell mediated immunity testing Most of the previous studies have focused on CTL responses to the CMV phosphoprotein pp65.15-17 However, since CD8+ T-cell responses to CMV often contain multiple antigen-specific reactivities, measurement of CMI using epitopes restricted to a single protein may not yield adequate results. In conjunction with Dr. Rajiv Khanna (Queensland Institute of Medical Research, Australia), and Cellestis Ltd (Sydney, Australia), we have done preliminary validation and assessment of a CMI (Quantiferon-CMV) assay in which we measure the IFN-γ responses to a range of T-cell epitopes of CMV viral proteins including pp65, pp50, the glycoprotein gB, and the immediate early IE-1 antigen that are specific for a wide range of HLA class I specificities [See Appendix Table 1]. The assay employs a peptide pool for stimulation of whole blood and is suitable for routine clinical use and evaluation in multicenter studies.
The Quantiferon-CMV assay has been compared to an ELISPOT assay in a study involving 37 healthy volunteers and 25 SOT recipients.18 In this study, the Quantiferon-CMV assay was at least as sensitive as the ELISPOT for some CMV epitopes, and more sensitive for other CMV epitopes. In addition, the Quantiferon-CMV results highly correlated with the CMV serostatus, in both healthy volunteers and transplant recipients. In another study,19 the Quantiferon-CMV assay was used in HIV-infected individuals with and without a history of CMV disease. The CMV specific immune response measured by the Quantiferon-CMV assay was higher in patients without a history of CMV disease, suggesting that a positive result of the Quantiferon-CMV may predict the likelihood for developing a protective immune response against CMV.
- Conditions
- Cytomegalovirus Infection
- Keywords
- liver transplant, lung transplant, kidney transplant, heart transplant, CMV CMI, Transplant
- Medical subject headings
- Cytomegalovirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Patients at high risk for CMV infection (CMV serostatus: D+/R-) who are expected to receive three months of antiviral prophylaxis. |
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jan 2009 (estimated)
- Study startMay 2008
- Primary completionMar 2012
- Study completionApr 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Cytomegalovirus InfectionStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 131 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alberta
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Deepali Kumar, University of Alberta
- Investigators
- Atul Humar, MD, Principal investigator, University of Alberta
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00817908
- Sponsor's protocol ID
- 7267
- Status last verified
- Apr 2012
- First submitted
- 15 Oct 2008
- Last updated
- 23 Apr 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
Razonable RR, Rivero A, Rodriguez A, Wilson J, Daniels J, Jenkins G, Larson T, Hellinger WC, Spivey JR, Paya CV. Allograft rejection predicts the occurrence of late-onset cytomegalovirus (CMV) disease among CMV-mismatched solid organ transplant patients receiving prophylaxis with oral ganciclovir. J Infect Dis. 2001 Dec 1;184(11):1461-4. doi: 10.1086/324516. Epub 2001 Oct 23.
PubMed 11709790Lowance D, Neumayer HH, Legendre CM, Squifflet JP, Kovarik J, Brennan PJ, Norman D, Mendez R, Keating MR, Coggon GL, Crisp A, Lee IC. Valacyclovir for the prevention of cytomegalovirus disease after renal transplantation. International Valacyclovir Cytomegalovirus Prophylaxis Transplantation Study Group. N Engl J Med. 1999 May 13;340(19):1462-70. doi: 10.1056/NEJM199905133401903.
PubMed 10320384Flechner SM, Avery RK, Fisher R, Mastroianni BA, Papajcik DA, O'Malley KJ, Goormastic M, Goldfarb DA, Modlin CS, Novick AC. A randomized prospective controlled trial of oral acyclovir versus oral ganciclovir for cytomegalovirus prophylaxis in high-risk kidney transplant recipients. Transplantation. 1998 Dec 27;66(12):1682-8. doi: 10.1097/00007890-199812270-00019.
PubMed 9884259Paya C, Humar A, Dominguez E, Washburn K, Blumberg E, Alexander B, Freeman R, Heaton N, Pescovitz MD; Valganciclovir Solid Organ Transplant Study Group. Efficacy and safety of valganciclovir vs. oral ganciclovir for prevention of cytomegalovirus disease in solid organ transplant recipients. Am J Transplant. 2004 Apr;4(4):611-20. doi: 10.1111/j.1600-6143.2004.00382.x.
PubMed 15023154Manuel O, Husain S, Kumar D, Zayas C, Mawhorter S, Levi ME, Kalpoe J, Lisboa L, Ely L, Kaul DR, Schwartz BS, Morris MI, Ison MG, Yen-Lieberman B, Sebastian A, Assi M, Humar A. Assessment of cytomegalovirus-specific cell-mediated immunity for the prediction of cytomegalovirus disease in high-risk solid-organ transplant recipients: a multicenter cohort study. Clin Infect Dis. 2013 Mar;56(6):817-24. doi: 10.1093/cid/cis993. Epub 2012 Nov 29.
PubMed 23196955
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Quantiferon - CMV and the Prediction of CMV Infection In High Risk Solid Organ Transplant Recipients
- ClinicalTrials.gov ID
- NCT00817908
- Acronym / sponsor ID
- 7267
- Conditions
- Cytomegalovirus Infection
- Keywords
- liver transplant, lung transplant, kidney transplant, heart transplant, CMV CMI, Transplant
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 131 participants (actual)
- Lead sponsor
- University of AlbertaUniversity, hospital or other
- Study start
- May 2008
- Primary completion
- Mar 2012 (actual)
- Study completion
- Apr 2012 (actual)
- First posted
- 7 Jan 2009 (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.
Cytomegalovirus (CMV) is a common cause of illness in patients who have undergone a transplant. Serious infections due to CMV can affect many parts of the body including the lungs, the gut, and the liver. Since transplant recipients are at risk for CMV or have evidence of infection with CMV, they are given an antiviral drug (usually ganciclovir or valganciclovir). Despite this, there are a chance that CMV infection may cause problems in the future. The purpose of this study is to assess how well patients'immune systems responds to the CMV virus, so that in the future it may be possible to predict which patients are at highest risk of CMV.
Detailed description
CMV is the most common viral infection after solid organ transplantation (SOT) and is associated with significant morbidity1. Without prophylaxis, most CMV disease occurs in the first 3 months post-transplant during the period of intense of immunosuppresion.2 SOT recipients at the greatest risk are those that are seronegative recipients of organs from seropositive donors (CMV D+/R-).3, 4 Antiviral agents have proven to be useful in the prevention of CMV infection and disease in SOT recipients, including the high-risk D+/R- patients.5-9 Upon completion of prophylaxis however, CMV infection and disease occurs in about 50% and 25-30% respectively of D+/R- SOT recipients within the first year after transplant [30% rate of investigator treated CMV disease in PV16000].9 The incidence of CMV infection following prophylaxis in D+/R- lung transplant recipients may be as high as 80%.10 As CMV disease occurring after prophylaxis will continue to impact morbidity and mortality in SOT recipients, it would be desirable to be able to predict which patient will develop this complication. Currently, there are no reliable methods that are routinely available to predict the risk of CMV infection or disease in an individual patient. CMV viral load testing after prophylaxis in D+/R- patients has been shown to have poor predictive value for subsequent CMV disease.11 CMV serology (a measure of humoral immunity) was also shown to be only of marginal use in predicting the risk of late onset disease.12 Cell mediated immunity (CMI) is known to be more important than humoral immunity in controlling CMV infection. CMV infection elicits a strong virus specific CD4+ and CD8+ T-cell response. CD8+ T-cell responses to the virus often contain multiple antigen-specific reactivities including to viral pp65 or IE-1 antigens as well as pp50, glycoprotein B, and IE-2 and other antigens.13 CD4+ T cells also play a part in CMV control via promotion of priming, expansion and maintenance of CD8+ CMV-specific CTLs.14 Measuring an individual's CMI response to CMV may be a useful predictor of the risk of CMV infection or disease after prophylaxis. Patients with a poor CMI response (especially a poor CD8+ T-cell response) could then be targeted with longer courses of antiviral prophylaxis.
Cell mediated immunity testing Most of the previous studies have focused on CTL responses to the CMV phosphoprotein pp65.15-17 However, since CD8+ T-cell responses to CMV often contain multiple antigen-specific reactivities, measurement of CMI using epitopes restricted to a single protein may not yield adequate results. In conjunction with Dr. Rajiv Khanna (Queensland Institute of Medical Research, Australia), and Cellestis Ltd (Sydney, Australia), we have done preliminary validation and assessment of a CMI (Quantiferon-CMV) assay in which we measure the IFN-γ responses to a range of T-cell epitopes of CMV viral proteins including pp65, pp50, the glycoprotein gB, and the immediate early IE-1 antigen that are specific for a wide range of HLA class I specificities [See Appendix Table 1]. The assay employs a peptide pool for stimulation of whole blood and is suitable for routine clinical use and evaluation in multicenter studies.
The Quantiferon-CMV assay has been compared to an ELISPOT assay in a study involving 37 healthy volunteers and 25 SOT recipients.18 In this study, the Quantiferon-CMV assay was at least as sensitive as the ELISPOT for some CMV epitopes, and more sensitive for other CMV epitopes. In addition, the Quantiferon-CMV results highly correlated with the CMV serostatus, in both healthy volunteers and transplant recipients. In another study,19 the Quantiferon-CMV assay was used in HIV-infected individuals with and without a history of CMV disease. The CMV specific immune response measured by the Quantiferon-CMV assay was higher in patients without a history of CMV disease, suggesting that a positive result of the Quantiferon-CMV may predict the likelihood for developing a protective immune response against CMV.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | – | –Patients at high risk for CMV infection (CMV serostatus: D+/R-) who are expected to receive three months of antiviral prophylaxis. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The study will aim to enrol 120 D+/R- transplant patients.
Key inclusion criteria (6 listed)
- Male or female patients who fulfill the following criteria are eligible for inclusion.
- CMV D+/R- liver, kidney, heart, pancreas, lungor combined transplant recipients
- All eligible patients must be scheduled to receive 3 months of either valganciclovir, oral ganciclovir, or intravenous ganciclovir prophylaxis.
- Able to give written informed consent
- Are willing and able to comply with the protocol
Key exclusion criteria (1 listed)
- Patient unwilling or unable to give informed consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2012.
- Background: PubMed 11709790Razonable RR, Rivero A, Rodriguez A, Wilson J, Daniels J, Jenkins G, Larson T, Hellinger WC, Spivey JR, Paya CV. Allograft rejection predicts the occurrence of late-onset cytomegalovirus (CMV) disease among CMV-mismatched solid organ transplant patients receiving prophylaxis with oral ganciclovir. J Infect Dis. 2001 Dec 1;184(11):1461-4. doi: 10.1086/324516. Epub 2001 Oct 23.
- Background: PubMed 10320384Lowance D, Neumayer HH, Legendre CM, Squifflet JP, Kovarik J, Brennan PJ, Norman D, Mendez R, Keating MR, Coggon GL, Crisp A, Lee IC. Valacyclovir for the prevention of cytomegalovirus disease after renal transplantation. International Valacyclovir Cytomegalovirus Prophylaxis Transplantation Study Group. N Engl J Med. 1999 May 13;340(19):1462-70. doi: 10.1056/NEJM199905133401903.
- Background: PubMed 9884259Flechner SM, Avery RK, Fisher R, Mastroianni BA, Papajcik DA, O'Malley KJ, Goormastic M, Goldfarb DA, Modlin CS, Novick AC. A randomized prospective controlled trial of oral acyclovir versus oral ganciclovir for cytomegalovirus prophylaxis in high-risk kidney transplant recipients. Transplantation. 1998 Dec 27;66(12):1682-8. doi: 10.1097/00007890-199812270-00019.
- Background: PubMed 15023154Paya C, Humar A, Dominguez E, Washburn K, Blumberg E, Alexander B, Freeman R, Heaton N, Pescovitz MD; Valganciclovir Solid Organ Transplant Study Group. Efficacy and safety of valganciclovir vs. oral ganciclovir for prevention of cytomegalovirus disease in solid organ transplant recipients. Am J Transplant. 2004 Apr;4(4):611-20. doi: 10.1111/j.1600-6143.2004.00382.x.
- Derived from this study: PubMed 23196955Manuel O, Husain S, Kumar D, Zayas C, Mawhorter S, Levi ME, Kalpoe J, Lisboa L, Ely L, Kaul DR, Schwartz BS, Morris MI, Ison MG, Yen-Lieberman B, Sebastian A, Assi M, Humar A. Assessment of cytomegalovirus-specific cell-mediated immunity for the prediction of cytomegalovirus disease in high-risk solid-organ transplant recipients: a multicenter cohort study. Clin Infect Dis. 2013 Mar;56(6):817-24. doi: 10.1093/cid/cis993. Epub 2012 Nov 29.
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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.
Atul Humar, MD principal investigator
University of Alberta
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cytomegalovirus Infection, run by University of Alberta at 1 site in Canada.
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 6 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: finished, as of the sponsor's last update on 23 Apr 2012. 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 Canada. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00817908, which also lists 5 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 23 Apr 2012; AzTrials last refreshed its copy on 8 Nov 2026.