Treating Kidney Donors With Valganciclovir to Reduce Viral Transmission to Recipients

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

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.

Study Overview

• Status: Completed
• Conditions: CMV Viremia; EBV Viremia
• Intervention / Treatment: Drug: Placebo; Drug: Valganciclovir

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.

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Eligible consenting kidney transplant donors who are randomized to receive placebo will be given 1 placebo in morning and 1 in evening for 14 days prior to transplant date	Drug: Placebo; 1 capsule twice a day for 14 days prior to transplant date
Experimental: Valganciclovir; Eligible consenting kidney transplant donors who are randomized to the experimental arm of the study will receive 450mg of Valganciclovir twice a day for 14 days prior to the transplant date	Drug: Valganciclovir; Valganciclovir 450mg twice a day for 14 days prior to transplant date

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of EBV or CMV Related Disease in Transplant Recipient	Incidence of EBV or CMV related disease in the transplant recipients of enrolled donors.	At least 1 year

Collaborators and Investigators

• Sponsor: University of Minnesota
• Investigators: Principal Investigator: Priya Verghese, MD, MPH, University of Minnesota

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: April 1, 2011
• First Submitted That Met QC Criteria: April 4, 2011
• First Posted (Estimate): April 5, 2011

Study Record Updates

• Last Update Posted (Actual): November 1, 2019
• Last Update Submitted That Met QC Criteria: October 30, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: EBV Viremia in posttransplant kidney recipients; CMV viremia in posttransplant kidney recipients
• Additional Relevant MeSH Terms: Pathologic Processes; Virus Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Viremia; Anti-Infective Agents; Antiviral Agents; Valganciclovir
• Other Study ID Numbers: 1012M93572