Lung transplant clinical trial network (LT-CTN)
Active Cooperative Agreement Awarded Last action
- Award ID
- U01AI163099
- Recipient
-
Duke University UEI TP7EK8DZV6N5
- Awarding agency
-
National Institute of Allergy and Infectious Diseases
National Institutes of Health, Department of Health and Human Services
- Obligated
- $48,469,967
Award facts
- Assistance listing
- 93.855 Allergy and Infectious Diseases Research
- Completion date 77% complete
- Funding
-
- $42,513,365.00 Federal
- $5,956,602.00 Non-federal
- Place of performance
- Durham, NC 27710, USA
Award details come from USAspending.gov.
Description
- Abstract
- This lung transplant clinical trials network (LT-CTN) ctot-CA consortium includes eight of the leading high- volume, research-oriented adult and pediatric lung transplant programs in north america. Long-term survival after lung transplantation is limited by chronic lung allograft dysfunction (CLAD), the final manifestation of chronic lung transplant rejection. CLAD is not effectively prevented by lung transplant immunosuppression, as over 50% of transplant patients develop CLAD within five years. Growing evidence suggests upregulation of inflammatory cytokines in the lung allograft contributes to CLAD development through innate immunity and allorecognition- driven adaptive immune responses. Our preliminary data demonstrate that post-transplant acute rejection (AR), lymphocytic bronchiolitis (LB), organizing pneumonia (OP), or acute lung injury (ALI) increase CLAD risk and are associated with elevations of types I & II cytokines in the lung fluid. Because type I/II cytokines share signaling through the janus kinase (JAK) family, blocking the relevant jaks could be an effective strategy to limit inflammatory cytokine responses and prevent CLAD. Our data demonstrate that itacitinib, a selective JAK1 and partial JAK2 inhibitor being tested in patients with bone marrow transplant, is effective in preventing AR in a fully mismatched murine orthotopic lung transplant model, and that JAK1 is highly overexpressed in human lung transplant CLAD. Thus, we hypothesize that addition of itacitinib to standard post-transplant immunosuppression will reduce inflammation due to cytokine signaling, diminish further innate and adaptive immune responses, and prevent CLAD. To test this, we propose to complete the inhibit-CLAD (itacitinib randomized, multi-center, double-blind, placebo-controlled trial to reduce lung inflammation and prevent CLAD) study, enrolling 450 bilateral lung transplant recipients over two years and randomizing 280 of those at higher CLAD risk (evidence of AR, LB, OP, or ALI) to treatment with itacitinib or placebo and follow-up over three to five years, to detect the primary outcome of CLAD. We also will collect biospecimens from all enrolled participants and conduct mechanistic studies using lung fluid and tissue from randomized patients to determine how innate immunity and adaptive immune responses that contribute to CLAD development are mitigated by selective JAK inhibition with itacitinib. Finally, as cytomegalovirus (CMV) is another key CLAD risk factor - and preventable - we propose a multi-center infectious disease study targeting prevention of CMV infection after lung transplant using novel measures of CMV-specific immunity to personalize antiviral prophylaxis duration. Our highly qualified team of investigators bring longstanding, collaborative, highly relevant experience, including leading the adult ctot-20 and-22 and the pediatric ctotc-03, -05, -08, and -11 studies. Successfully completed, the studies now proposed have potential to transform clinical practice, improve lung transplant outcomes, and expand treatment paradigms for immune suppression and anti-viral prophylaxis after solid organ transplantation.
Transactions
| Action | Federal | Non-federal | Date |
|---|---|---|---|
| Amendment | $186,222 | $0 | |
| Amendment | $3,209,216 | $0 | |
| Amendment | $3,209,216 | $0 | |
| Amendment | $0 | $0 | |
| Amendment | $0 | $0 | |
| Amendment | $0 | $0 | |
| Amendment | $297,730 | $0 | |
| Amendment | $297,730 | $0 | |
| Amendment | $297,730 | $0 | |
| Amendment | $297,730 | $0 | |
| Amendment | $3,897,643 | $0 | |
| Amendment | $3,897,643 | $0 | |
| Amendment | $3,897,643 | $0 | |
| Amendment | $3,897,643 | $0 | |
| Amendment | $1,266,035 | $0 | |
| Amendment | $2,973,990 | $0 | |
| Amendment | $2,973,990 | $0 | |
| Amendment | $2,975,390 | $0 | |
| Amendment | $2,975,390 | $2,975,390 | |
| Amendment | $0 | $0 | |
| Amendment | $0 | $0 | |
| Amendment | $0 | $0 | |
| Amendment | $2,981,212 | $0 | |
| Original award | $2,981,212 | $2,981,212 |
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Subawards
| Subrecipient | Amount | Awarded |
|---|---|---|
| University Of California, LOS Angeles | $2,908,018 | |
| The Washington University | $580,357 | |
| The Johns Hopkins University | $833,371 | |
| University Health Network | $1,623,740 | |
| The Trustees Of The University Of Pennsylvania | $1,825,901 | |
| New York University | $320,000 | |
| Vanderbilt University Medical Center | $466,600 | |
| Cleveland Clinic Lerner College Of Medicine Of Case Western Reserve University | $1,476,160 | |
| Childrens Hospital Medical Center | $379,307 | |
| The Leland Stanford Junior University | $235,000 | |
| Regents Of The University Of Minnesota | $155,000 |
Show all 11
Quick answers
Who received award U01AI163099?
U01AI163099 was awarded to Duke University by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on August 13, 2021.
How much is award U01AI163099 worth?
$48,469,967 has been obligated on U01AI163099: $42,513,365 in federal funding and $5,956,602 in non-federal funding.
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