Clinical trial NCT01329185: Treating Kidney Donors With Valganciclovir to Reduce Viral Transmission to Recipients
Official title: Double Blinded Placebo Controlled Study to Assess Clinical and Antiviral Activity of Valganciclovir (VAL) in Solid Organ Transplant Donors to Reduce Viral Transmission From Donor to Recipient
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: EBV Viremia
CMV Viremia
Keywords: EBV Viremia in posttransplant kidney recipients
CMV viremia in posttransplant kidney recipients
Lead sponsor: University of Minnesota
Sponsor class: OTHER
First posted: 2011-04-05
Enrollment: 17
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The aim of our study is to reduce viral (CMV and EBV) transmission from donor to recipient. The discovery that anti-retroviral therapy to mothers with HIV reduced transmission of the virus to their babies was pivotal to the prevention of AIDS and so along the same lines the investigators will test the hypothesis that 14 days of the anti-viral Valganciclovir (VAL) to kidney donors prior to the transplant compared to placebo will reduce EBV and CMV viremia in the 1st year posttransplant in pediatric kidney recipients.

Detailed description: The potency of new immunosuppressive agents has reduced the risk of the body's immune system rejecting a transplanted kidney. However, this has come with a price. Kidney transplant recipients now face a higher risk of serious infections and related malignancies.

Viral infections are a significant cause of posttransplant morbidity and mortality and two of the herpes viruses have the greatest impact: Epstein-Barr virus (EBV) and Cytomegalovirus (CMV). CMV disease can manifest posttransplant as fever, leukopenia, or mild to severe organ involvement (including pneumonitis, hepatitis, pancreatitis, colitis, meningoencephalitis, and rarely myocarditis). EBV can present posttransplant as infectious mononucleosis syndrome, hepatitis and, in the worse case scenario, a potentially fatal lymphoproliferative disorder called Post-Transplant Lymphoproliferative Disease (PTLD). Moreover, subclinical CMV and/or EBV viremia have been associated with deterioration in kidney function in kidney transplant recipients. Thus, the potential negative impact of these viruses on the lives of transplant recipients is profound and, unfortunately, the complications of these post-transplant viral infections are common and occur despite standard antiviral prophylaxis in the first year posttransplant.

These viral infections, in most instances, originate from the donor organ where these viruses reside in a dormant state, counterbalanced by the donor's healthy immune system. Upon transplantation into the recipient, whose immune system is then severely suppressed by anti-rejection drugs, these viruses become activated, often leading to the above described complications.

The aim of our study is to reduce viral (CMV and EBV) transmission from donor to recipient. The discovery that anti-retroviral therapy to mothers with HIV reduced transmission of the virus to their babies was pivotal to the prevention of AIDS and so along the same lines the investigators will test the hypothesis that 14 days of the anti-viral Valganciclovir (VAL) to kidney donors prior to the transplant compared to placebo will reduce EBV and CMV viremia in the 1st year posttransplant in pediatric kidney recipients. We aim to enroll 20 donor-recipient pairs.

Eligibility criteria: Inclusion criteria:

* Any person approved as a kidney transplant donor with a recipient who has never undergone a previous transplantation
* Kidney transplant donor must be 18 years old or older
* The kidney transplant donor must be positive for CMV IgG and / or EBV IgG
* The donor must be to a recipient that is discordantly seronegative for the virus for which the donor is seropositive (D+ R-)
* They must have provided signed informed consent
* The potential donors must be willing to contribute samples of blood and oral washings at regular intervals
* The potential donor must state willingness to use effective contraception during treatment and 30 days following receiving the study drug/placebo
* All females must have a negative pregnancy test
* Person must have estimated creatinine clearance (Cockcroft and Gault method) \>= 60 ml/min
* Person must have Absolute neutrophil count \>= 1000 cells/uL
* Person must have Platelets \>= 100,000/uL
* Person must have Hemoglobin \>= 9.5 g/dL

Exclusion criteria:

* Any potential kidney transplant donor who is seronegative for both CMV \& EBV IgG
* Any potential kidney transplant donor who is receiving or have received anti-herpes medication in the past week
* Any potential kidney transplant donor to a recipient who has received a previous solid organ transplant
* Any potential kidney transplant donor who is immunosuppressed due to medical disease and/or immunosuppressive or immunomodulating medications
* Any potential kidney transplant donor who is breast feeding during the study
* Any potential kidney transplant donor who is on corticosteroids

Primary outcomes:
measure: Incidence of EBV or CMV Related Disease in Transplant Recipient
timeFrame: At least 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
Study officials:
affiliation: University of Minnesota
name: Priya Verghese, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: