PREDICT Cytomegalovirus (CMV) (PREDICT CMV)

• ClinicalTrials.gov Identifier: NCT03300882
• Recruitment Status: Completed
• First Posted: October 4, 2017
• Last Update Posted: August 6, 2020
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Clinical Trials in Organ Transplantation; Rho Federal Systems Division, Inc.
• Information provided by (Responsible Party): National Institute of Allergy and Infectious Diseases (NIAID)

Study Description

Brief Summary:

The overall objective of this study is to establish a personalized test to measure individualized cytomegalovirus (CMV) specific immunity in lung transplant recipients in an effort to guide antiviral prophylaxis duration in clinical practice.

Targeted participants are those:

• enrolled in clinical research study CTOT-20 (Clinical Trials.gov ID: NCT02631720) who
• are CMV recipient positive by serology as determined using methods in accordance with current local organ procurement organization policies.

Condition or disease	Intervention/treatment
Lung Transplant	Other: Procedure

Detailed Description:

Cytomegalovirus (CMV) is a common virus. The virus is spread from one person to another through infected body fluids. In those with a normal immune system, CMV does not cause much of a problem. The immune system keeps the virus under control so most people do not have any symptoms. Once infected, the virus usually stays dormant (inactive) in the body for a person's entire life. This means some of the cells in the body are infected and the virus can become active again.

Lung transplant recipients take anti-rejection medicines to prevent the body from rejecting the transplanted lung(s). Although anti-rejection medications help protect the transplanted lung(s) from the body's immune system, these medications also decrease the body's ability to fight infections. This reduces the immune system's ability to control viruses like CMV. Many transplant recipients take an antiviral medication early after transplant to help the body control the CMV virus. This is the time that risk of infection would be highest. Sometimes recipients get an active CMV infection after stopping these medicines. If this happens, the infection is treated and monitored.

In this study, investigators are trying to determine whether a blood test can predict development of active CMV infection in lung transplant recipients. Specifically, the clinical research study will prospectively assess the performance of an immune signature based on the "ex vivo" measurement of T cell CMV specific immunity in predicting freedom from future CMV infections among recipient positive (R+) lung transplant participants receiving standard durations of valganciclovir prophylaxis.

Study Design

• Study Type: Observational
• Actual Enrollment: 84 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Prospective Multicenter Cytomegalovirus (CMV) Specific Immune Monitoring to Predict Patient Risk After Lung Transplantation (CTOT-22)
• Actual Study Start Date: October 31, 2017
• Actual Primary Completion Date: November 25, 2019
• Actual Study Completion Date: November 25, 2019

Groups and Cohorts

Group/Cohort

Intervention/treatment

CMV+ First Lung Transplant Recipients; Participants enrolled in one of four North American sites in clinical research study CTOT-20 (Clinical Trials.gov ID: NCT02631720) who are cytomegalovirus positive by serology (e.g., CMV Recipient positive).

Other: Procedure; Serial blood draws. Participants will be enrolled either pre-transplant or within 45 days post-transplant and will be followed over the course of 18 months post transplant. Protocol mandated serial measurement of cytomegalovirus (CMV)-specific immune signature will occur pre-transplant (as applicable) and at post-transplant timepoint months 2, -3, -6, -9, -12 and -18.; Other Names: Serial blood draws; Phlebotomy; Venipuncture

Outcome Measures

Primary Outcome Measures :

1. Time from CMV Prophylaxis Discontinuation Post-Transplant to First Detection of CMV Infection or CMV Disease within 6 months Post CMV Prophylaxis Discontinuation [ Time Frame: From CMV Prophylaxis Discontinuation to 6 Months Post CMV Prophylaxis Discontinuation ]
   Participants will be evaluated for CMV infection or disease according to each center's standard of care clinical protocol. All centers have aligned their clinical practice to include, at a minimum, a CMV infection and a CMV disease assessment at the time of prophylaxis discontinuation, monthly for the first 6 months after discontinuation, and quarterly after that up to 18 months post transplantation.
2. Time from CMV Prophylaxis Discontinuation Post-Transplant to First Detection of CMV Infection or CMV Disease Within 18 Months Post-Transplant [ Time Frame: From CMV Prophylaxis Discontinuation to 18-Months Post-Transplant ]
   Participants will be evaluated for CMV infection or disease according to each center's standard of care clinical protocol. All centers have aligned their clinical practice to include, at a minimum, a CMV infection and a CMV disease assessment at the time of prophylaxis discontinuation, monthly for the first 6 months after discontinuation, and quarterly after that up to 18 months post transplantation.

Biospecimen Retention:   Samples With DNA

Peripheral blood mononuclear cells (PBMCs) and plasma.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Adult lung transplant recipients undergoing lung transplant at one of the four participating centers and concurrently enrolled in CTOT-20 (Clinical Trials.gov ID: NCT02631720).

Criteria

Inclusion Criteria:

Individuals who meet all of the following criteria are eligible for enrollment as study participants:

• Must be able to understand and provide written informed consent;
• Anticipated listing for lung transplantation OR listed for lung transplant OR is within 45 days of having received a single or bilateral cadaveric donor lung transplant;
• Undergoing first lung transplant operation;
• Transplant surgery to be performed or performed at enrolling center;
• Concurrent participation in CTOT-20 (Clinical Trials.gov ID: NCT02631720); and

• CMV-seropositive lung transplant recipient, using methods in accordance with current local organ procurement organization policies.

  • Note: Concurrent participation in immune monitoring studies or interventional device trials are permitted.

Exclusion Criteria:

Individuals who meet any of the following criteria are not eligible for enrollment as study participants:

• Unwilling to enroll in CTOT-20 (Clinical Trials.gov ID: NCT02631720);
• Multi-organ recipient;
• Prior recipient of any solid organ transplant, including prior lung transplant;
• Prior or concurrent recipient of bone marrow transplant;
• Human Immunodeficiency Virus (HIV) infection;
• Pregnant or planned pregnancy;
• Any condition that, in the investigator's opinion, would make it unlikely for the recipient to complete follow up procedures or complete the study; or
• Participation in an investigational drug trial at the time of enrollment visit.

Contacts and Locations

Locations

United States, Maryland

Johns Hopkins Hospital: Transplantation

Baltimore, Maryland, United States, 21287

United States, North Carolina

Duke University Medical Center: Transplantation

Durham, North Carolina, United States, 27710

United States, Ohio

Cleveland Clinic Foundation: Transplantation

Cleveland, Ohio, United States, 44195

Canada

Toronto General Hospital: Transplantation

Toronto, Canada, M5G 2C4

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Clinical Trials in Organ Transplantation

Rho Federal Systems Division, Inc.

Investigators

• Study Chair: Laurie Snyder, MD, MHS; Duke University Medical Center: Transplantation
• Study Chair: Scott Palmer, MD, MHS; Duke University Medical Center: Transplantation

More Information

Additional Information:

National Institute of Allergy and Infectious Diseases (NIAID) 

Division of Allergy, Immunology, and Transplantation (DAIT) 

Clinical Trials in Organ Transplantation (CTOT) 

Publications:

Snyder LD, Chan C, Kwon D, Yi JS, Martissa JA, Copeland CA, Osborne RJ, Sparks SD, Palmer SM, Weinhold KJ. Polyfunctional T-Cell Signatures to Predict Protection from Cytomegalovirus after Lung Transplantation. Am J Respir Crit Care Med. 2016 Jan 1;193(1):78-85. doi: 10.1164/rccm.201504-0733OC.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT03300882
• Other Study ID Numbers: DAIT CTOT-22; NIAID CRMS ID#: 38277 ( Other Identifier: DAIT NIAID )
• First Posted: October 4, 2017
• Last Update Posted: August 6, 2020
• Last Verified: August 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Study co-enrollment (CTOT-20 and CTOT-22); cytomegalovirus (CMV); CMV seropositive positive recipient; CMV infection; CMV-specific immunity; immunologic monitoring

Additional relevant MeSH terms:

Cytomegalovirus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections