U24HL154946
Cooperative Agreement
Overview
Grant Description
2/2 Doxycycline for Emphysema in People Living with HIV: The DEPTH Trial
The DEPTH Trial represents an innovative approach to slowing the progression of emphysema in people living with HIV (PLWH), a population that has accelerated disease progression for which there is no targeted therapy. With our CCC collaborators, we propose a Phase II, multi-center, randomized, double-blind, placebo-controlled trial of doxycycline 100 mg PO BID to slow the progression of emphysema as quantified by diffusing capacity for carbon monoxide (DLCO) among PLWH who are current or former smokers.
Participants will be stratified by smoking status (current vs former smoker) and clinical site, utilizing dynamic randomization. The primary endpoint of the study is the rate of decline (slope) of percent predicted DLCO corrected for hemoglobin, carboxyhemoglobin, and barometric pressure over the 72-week treatment period.
Our clinical collaborators have successfully demonstrated the feasibility of this study in their NHLBI-funded pilot study to test the safety and tolerability of doxycycline in 27 individuals over 24 weeks (NCT 01744093) and have assembled a group of experienced clinical sites. The DEPTH Trial will extend their promising pilot data to a formal Phase II clinical trial.
An experienced Data Coordinating Center (DCC) with strong statistical leadership and expertise is key in both design and analysis, particularly when unanticipated issues arise during the conduct of a clinical trial. The University of Michigan (UM) Statistical Analysis of Biomedical and Educational Research (SABER) Unit in a top-ranked Department of Biostatistics will serve as DCC, bringing together an experienced group of faculty and staff in biostatistics, project management, study monitoring, database design and data management, software development, and research administration. SABER has a strong track record of collaborations with Weill Cornell Medicine Pulmonary Team as the Clinical Coordinating Center (CCC).
The overarching goal of the UM DCC is to collaborate with study investigators, the CCC, and NHLBI to enable successful achievement of the study on time and within budget. We will accomplish these goals through the three specific aims:
(1) Enhance scientific rigor by providing statistical and clinical trials methodological expertise to design, analyze, and disseminate research findings.
(2) Ensure the collection of timely, accurate, and reproducible data, and maximize adherence to the study protocol.
(3) Provide established infrastructure and services for study administration and operations and for communication among study stakeholders.
Our leadership, experience, and expertise will promote collaborations, encourage scientific productivity, and facilitate timely dissemination of findings on the benefits of doxycycline in PLWH who have emphysema. We anticipate that upon completion of this proposed study, our data will support repurposing the inexpensive antibiotic doxycycline to slow emphysema progression in PLWH and demonstrate that it is safe and well-tolerated.
The DEPTH Trial represents an innovative approach to slowing the progression of emphysema in people living with HIV (PLWH), a population that has accelerated disease progression for which there is no targeted therapy. With our CCC collaborators, we propose a Phase II, multi-center, randomized, double-blind, placebo-controlled trial of doxycycline 100 mg PO BID to slow the progression of emphysema as quantified by diffusing capacity for carbon monoxide (DLCO) among PLWH who are current or former smokers.
Participants will be stratified by smoking status (current vs former smoker) and clinical site, utilizing dynamic randomization. The primary endpoint of the study is the rate of decline (slope) of percent predicted DLCO corrected for hemoglobin, carboxyhemoglobin, and barometric pressure over the 72-week treatment period.
Our clinical collaborators have successfully demonstrated the feasibility of this study in their NHLBI-funded pilot study to test the safety and tolerability of doxycycline in 27 individuals over 24 weeks (NCT 01744093) and have assembled a group of experienced clinical sites. The DEPTH Trial will extend their promising pilot data to a formal Phase II clinical trial.
An experienced Data Coordinating Center (DCC) with strong statistical leadership and expertise is key in both design and analysis, particularly when unanticipated issues arise during the conduct of a clinical trial. The University of Michigan (UM) Statistical Analysis of Biomedical and Educational Research (SABER) Unit in a top-ranked Department of Biostatistics will serve as DCC, bringing together an experienced group of faculty and staff in biostatistics, project management, study monitoring, database design and data management, software development, and research administration. SABER has a strong track record of collaborations with Weill Cornell Medicine Pulmonary Team as the Clinical Coordinating Center (CCC).
The overarching goal of the UM DCC is to collaborate with study investigators, the CCC, and NHLBI to enable successful achievement of the study on time and within budget. We will accomplish these goals through the three specific aims:
(1) Enhance scientific rigor by providing statistical and clinical trials methodological expertise to design, analyze, and disseminate research findings.
(2) Ensure the collection of timely, accurate, and reproducible data, and maximize adherence to the study protocol.
(3) Provide established infrastructure and services for study administration and operations and for communication among study stakeholders.
Our leadership, experience, and expertise will promote collaborations, encourage scientific productivity, and facilitate timely dissemination of findings on the benefits of doxycycline in PLWH who have emphysema. We anticipate that upon completion of this proposed study, our data will support repurposing the inexpensive antibiotic doxycycline to slow emphysema progression in PLWH and demonstrate that it is safe and well-tolerated.
Funding Goals
NOT APPLICABLE
Grant Program (CFDA)
Awarding / Funding Agency
Place of Performance
Ann Arbor,
Michigan
481091276
United States
Geographic Scope
Single Zip Code
Related Opportunity
Analysis Notes
Amendment Since initial award the total obligations have increased 325% from $863,939 to $3,669,568.
Regents Of The University Of Michigan was awarded
2/2 Doxycycline for Emphysema in People Living with HIV: The DEPTH Trial
Cooperative Agreement U24HL154946
worth $3,669,568
from National Heart Lung and Blood Institute in September 2021 with work to be completed primarily in Ann Arbor Michigan United States.
The grant
has a duration of 5 years and
was awarded through assistance program 93.837 Cardiovascular Diseases Research.
The Cooperative Agreement was awarded through grant opportunity Data Coordinating Center for Multi-Site Investigator-Initiated Clinical Trials (Collaborative U24 Clinical Trial Required).
Status
(Ongoing)
Last Modified 9/5/24
Period of Performance
9/17/21
Start Date
8/31/26
End Date
Funding Split
$3.7M
Federal Obligation
$0.0
Non-Federal Obligation
$3.7M
Total Obligated
Activity Timeline
Subgrant Awards
Disclosed subgrants for U24HL154946
Transaction History
Modifications to U24HL154946
Additional Detail
Award ID FAIN
U24HL154946
SAI Number
U24HL154946-2477213970
Award ID URI
SAI UNAVAILABLE
Awardee Classifications
Public/State Controlled Institution Of Higher Education
Awarding Office
75NH00 NIH NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
Funding Office
75NH00 NIH NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
Awardee UEI
GNJ7BBP73WE9
Awardee CAGE
03399
Performance District
MI-06
Senators
Debbie Stabenow
Gary Peters
Gary Peters
Budget Funding
| Federal Account | Budget Subfunction | Object Class | Total | Percentage |
|---|---|---|---|---|
| National Heart, Lung, and Blood Institute, National Institutes of Health, Health and Human Services (075-0872) | Health research and training | Grants, subsidies, and contributions (41.0) | $1,861,606 | 100% |
Modified: 9/5/24